CA2242097C - Imidazotriazolopyrimidines, process for preparing them and their use as pharmaceutical compositions - Google Patents

Abstract

The invention relates to new imidazotriazolopyrimidinone derivatives and fundamental imidazotriazolopyrimidinone substances, processes for preparing them and their use as pharmaceutical compositions.

Description

25771-646(S) Imidazotriazotopyrimidines, processes for preparing them and their use as pharmaceutical compositions The invention relates to new imidazotriazolopyrimidinone derivatives and fundamental imidazotriazolopyrimidinone substances, processes for preparing them and their use as pharmaceutical compositions.
~o The new imidazotriazolopyrimidinone derivatives have the structure of general formula (I):
p R' Rv N: N 2 I ,:~-- R
R.N-. N
._ N R3 6' R - (l) '! 5 wherein R' or R3 denotes hydrogen, an optionally substituted C~_~o-alkyl, C2_~o-alkenyl or C2.~fl-alkynyl, an optionally substituted C3_8-cycloalkyl, an optionally substituted Cø8-cycloalkenyl or an optionally substituted Cs.s-cycloalkynyl;
R' or R3 denotes an optionally substituted Cs-~o-aryl-C~.salkyl, Cs_~o-aryl-C2~-alkenyl, Cs_~o-aryl-C2.s-alkynyl, an optionally substituted Cs_~o-aryl or an optionally substituted heteroaryl, an optionally substituted 5-, 6- or 7-membered heterocyclic group which contains as 2s heteroatoms one or more atoms from the group comprising nitrogen, oxygen or sulphur, the heterocycle being linked via a carbon atom of the ring;
R' or R3 - denotes an optionally substituted C~_~o-alkyloxycarbonyl, an optionally 3o substituted C2.~o-alkenyloxycarbonyl, an optionally substituted C2_~o-alkynyloxycarbonyl, an optionally substituted C3_e-cycloalkyloxycarbonyl, an optionally substituted Cs.io-aryloxycarbonyl, an optionally substituted 25771-646(S1 Cs.,o-aryl-C,.e-alkyloxycarbonyl, A-O-CO- wherein A denotes an optionally substituted 5-, 6- or 7-membered heterocyclic group which contains as heteroatoms one or more atoms selected from the group comprising nitrogen, oxygen or sulphur, wherein A is linked via a carbon atom of the ring, R' or R' is ~ optionally substituted C,.,o-alkylsvdphonyl, Cz.,o-alkenylsulphonyl.
Cz malkynYlsul~w~yl, an optionally substituted to C3a-cycloalkyls~phonyl, an optionally substituted Ce.,o-arylsulphonyl, an optionally substituted Cs.,o-~yl-C~.e-alkytsulphonyi, a group A-SOr wherein A is as troreinbefore defined and is linked via a carbon atom of the ring;
s5 R' or R' denotes an optionally substituted C,.,o-aikylcarbonyl, an optionally substituted Cz.,o-alkenyicarbonyl, an optionally substituted G=_,a-alkynylcarbonyl, an optionally substituted C~.s-cycloalkylcarbonyl, an optionally substituted Cs.,o-arylcarbonyl, an optionally substituted Ce.,o-aryl-C,.e-aikylcarbonyi, a group A-CO- wherein A is as 2o herainbefore defined; or R' or R3 denotes a group of general. formula H
N

25 wherein R denotes hydrogen, phenyl, substituted phenyl, an optionally substituted ber~zyi, an optionally substituted Cs.e-cydoaikyl group, a branched or tut~nched C,.~o-alkyl, PAY C~--alkyl, Cs.,o-alkenyl or Cz.,o-alkynyi group which may optionally be substituted by hydroxy.
3o phenyl, substituted phenyl, amino or substituted amino;
RZ . denotes hydrogen, hydroxy, amino, halogen, vitro, CF3, COOH, mercapto, C,.e-alkylmercapto, an optionally substituted C,.,o-alkyl, an optionally substituted Cz.,o-alkenyl, an optionally substituted 35 C2.,o-alkynyl, an optionally substituted C~.e-cycloalkyl, an optionally substituted Cs-0-cycloalkanone, an optionally substituted Cps-cycloalkenyl, an optionally substituted Cs_$-cycloalkynyl, an optionally substituted Cs_~o-aryl, an optionally substituted Cs_~o-aryl-C~_s-alkyl, Cs_~o-aryl-Cz_s-alkenyl, Cs_~o-aryl-Cz_s-alkynyl, C3$-cycloalkyl-C~_s-alkyl, C3$-cycloalkyl-Cz_s-alkenyl, or C3_s-cycloalkyl-Cz_s-alkynyl;
Rz denotes an optionally substituted 5-, 6- or 7-membered heterocyclic group which contains as heteroatom one or more atoms selected from ~o the group comprising nitrogen, oxygen or sulphur, wherein the nitrogen may optionally be substituted and the heterocyclic group may be linked via a carbon or nitrogen atom directly or via a C~_s-alkyl, Cz_s-alkenyl or Cz~-alkynyl bridge;
Rz denotes an optionally substituted C~_~o-alkylsulphonyl, Cz_~o-alkenylsulphonyl or Cz_~o-alkynylsulphonyl, an optionally substituted C3_$-cycloalkylsulphonyl, an optionally substituted Cs_~o-arylsulphonyl, an optionally substituted heteroarylsulphonyl or an optionally substituted Cs-~o-aryl-C~_s-alkylsulphonyl;
Rz denotes an optionally substituted C~_~o-alkylsulphonyloxy, Cz_~o-alkenylsulphonyloxy or Cz_~o-alkynylsulphonyloxy, an optionally substituted C3_$-cycloalkylsulphonyloxy, an optionally substituted Cs_~o-arylsulphonyloxy, an optionally substituted Cs_~o-aryl-C~_s-alkylsulphonyloxy or an optionally substituted heteroarylsulphonyloxy;
Rz denotes an optionally substituted C,_~o-alkylsulphonylamino, Cz_~o-alkenylsulphonylamino or Cz_~o-alkynylsulphonylamino, an optionally substituted C3_$-cycloalkylsulphonylamino, an optionally substituted Cs_~o-arylsulphonylamino, an optionally substituted Cs_~o-aryl-C~_s-alkylsulphonylamino, or an optionally substituted heteroarylsulphonylamino;
Rz denotes an optionally substituted C~_~o-alkylaminocarbonyl, C~-~o-dialkylaminocarbonyl, C~_~o-alkyl-Cz_~o-alkenylaminocarbonyl, Cz_~o-alkenylaminocarbonyl, Cz_~o-dialkenylaminocarbonyl, Cz_~o-alkynylaminocarbonyl or C~_~o-alkyl-Cz_~o-alkynylaminocarbonyl, an optionally substituted Cs$-cycloalkylaminocarbonyl, an optionally substituted Cs_~o-arylaminocarbonyl, an optionally substituted Cs_~o-aryl-C~-s-alkylaminocarbonyl, or an optionally substituted heteroarylaminocarbonyl;
R2 denotes an optionally substituted C~_~o-alkyloxycarbonylamino, C2_~o-alkenyloxycarbonylamino or C2_~o-alkynyloxycarbonylamino, an optionally substituted C3_s-cycloalkyloxycarbonylamino, an optionally substituted Cs_~o-aryloxycarbonylamino, an optionally substituted o Cs_~o-aryl-C~~-alkyloxycarbonylamino or an optionally substituted heteroaryloxycarbonylamino;
R2 denotes an optionally substituted C~_~o-alkylaminocarbonyloxy, C2_~o-alkenylaminocarbonyloxy or C2_~o-alkynylaminocarbonyloxy, an optionally substituted Cps-cycloalkylaminocarbonyloxy, an optionally substituted Cs_~o-arylaminocarbonyloxy, an optionally substituted Cs_~o-aryl-C~_s-alkylaminocarbonyloxy or an optionally substituted heteroarylaminocarbonyloxy;
2o R2 denotes an optionally substituted C1_~o-alkyl-N-amidino, C2_~o-alkenyl-N-amidino or C2_~o-alkynyl-N-amidino, an optionally substituted Cs~-cycloalkyl-N-amidino, an optionally substituted Cs-~o-aryl-N-amidino, an optionally substituted Cs_~o-aryl-C~_s-alkyl-N-amidino or an optionally substituted heteroaryl-N-amidino;
R2 denotes an optionally substituted C~_~o-alkyloxy, C2_~o-alkenyloxy or CZ_~o-alkynyloxy, an optionally substituted Cs_s-cycloalkyloxy, an optionally substituted Cs_~o-aryloxy, an optionally substituted o Cs_~o-aryl-C~_s-alkyloxy or an optionally substituted heteroaryloxy;
R2 denotes an optionally substituted C~_~o-alkyloxycarbonyl, C2_~o-alkenyloxycarbonyl or C2_~o-alkynyloxycarbonyl, an optionally substituted C~$-cycloalkyloxycarbonyl, an optionally substituted Cs_~o-aryloxycarbonyl, an optionally substituted Cs_~o-aryl-C~-s-alkyloxycarbonyl or an optionally substituted heteroaryloxycarbonyl;

R2 denotes an optionally substituted C~_~o-alkylcarbonyloxy, C2-~o-alkenylcarbonyloxy or C2_~o-alkynylcarbonyloxy, an optionally substituted Cs_$-cycloalkylcarbonyloxy, an optionally substituted 5 C6_~o-arylcarbonyloxy, an optionally substituted C6_~o-aryl-C~_6-alkylcarbonyloxy or an optionally substituted heteroarylcarbonyloxy;
R2 denotes an optionally substituted C~_~o-alkylthio, C2_~o-alkenylthio or C2_~o-alkynylthio, an optionally substituted Cs~-cycloalkylthio, an optionally substituted Cs_~o-arylthio, an optionally substituted C6_~o-aryl-C~_6-alkylthio or an optionally substituted heteroarylthio;
R2 denotes an optionally substituted amine, preferably NR$R9;
RZ denotes an optionally substituted group of the formula O
/ ~ ~(CH2)~,2 / ~ ~ \ /
\ O \ / \
2o R2 denotes an optionally substituted group of the formula (CH"), ., (CH2)~.2 (CH2)~.2 _, -r~4 ~ ll -r wherein Y is a single bond or an alkylene, an alkenylene or an alkynylene having up to 6, preferably up to 4 carbon atoms in the chain;

25771-646(S) R2 denotes an optionally substituted group of the formula (CH2),.2 Y . Y I
C~..CQ p~yl C,-CQ-Alkyl wherein Y is a single taond or an alkylene, an alkenylene or an alkynylene having up to 6, preferably up to 4 carbon atoms in the chain; or R2 denotes an optionally su~tuted group of the formula ~o -Y ~ CHnoa.t Y-C~ H
(C Z~a.,.z (CHz~o., z w (CHZ)o,~.2 --Y- .
i Y~
UHz~o., .z wherein Y is a single bond or an alkylene, an alkenylene or an alkynyiene having up to 6, preferably up to 4 carton atoms in the chain;
R' or Rs denotes a hydrogen atom, ~ optionally substituted C,_,o-alkyl.
Cz.,o-alkenyl or C2.ro-, a~ opa~lY Substituted C~-cycfoalkyl, 2o an opfyonaily substituted C~a-cycloalkanyl or an optionally substituted C~-cyctoalkynyl, an optimally substituted Cs.,o-arYl-C,.e-alkyl, Ca.;Q-aryl-C=.e-alkenyi, C~.,o-aryl-CZ.e-alkynyl, an optionally substituted C~.,.a-ary1 or an optionally substituted heteroaryl;
25 R4 or R5 denotes an optionally substituted 5-, 6- or 7-membered heterocyclic group which contains as heteroatoms one of more atoms selected from the group comprising nitrogen, oxygen or sulphur, the heterocyclic group being bound via a carbon atom of the ring;

25771-646 (S) R4 or RS denotes an optionally substituted C,_,o-alkyloxycarbonyl, an optionally substituted Cz_,o-alkenyioxycarbonyl, an optionally substituted Cz_,o-alkynyloxycarbonyl, an optionally substituted C~a-cycloalkyloxycarbonyl, an optionally substituted C~,o-aryl-C,~-alkyloxycarbonyl, an optionally substituted Cs., o-arYloxycarbonyl;
R4 or RS denotes A-O-CO- wherein A denotes an optionally substituted 5-, 6- or p 7-membered heterocydic group which contains as heteroatoms one or more atoms selected from the group comprising nitrogen, oxygen or sulphur;
R4 or RS denotes an optionally substituted C,_,o-alkylsulphonyl, ~5 Cz_,o-alkenyisuiphonyl, Cz_,o-alkynylsulphonyl, an optionally substituted C3.s-cycloalkylsulphonyl, an optionally substituted C~,o-aryisulphonyl, a group A-SOz- wherein A is as hereinbefore defined and is linked via a carbon atom of the ring;
2o R4 or RS denotes an optionally substituted C,_,o-alkylcarbonyl, an optionally substituted Cz_,o-alkenylcarbonyl, an optionally substituted C2_,o-alkynylcarbonyl, an optionally substituted C3.$-cycloalkylcarbonyl, an optionally substituted Cs_,o-arylcarbonyl, an optionally substituted Cs.,o-ar'YI-C,-s-alkylcarbonyl, a group A-CO- wherein A is as 25 hereinbefore defined; or R4 or RS denotes a group of general formula H
~N

wherein R denotes hydrogen, phenyl, substituted phenyl, an optionally substituted benzyl, an optionally substituted Cs-s-cycloalkyl group, a branched or unbranched C,_,o-alkyl, preferably C,~-alkyl, Cz_,o-alkenyi or Cz.~o-alkynyl group, which may optionally be substituted by hydroxy, phenyl, substituted phenyl, amino or substituted amino;

Rs denotes hydrogen, hydroxy, -CHO, amino, halogen, nitro, CF3, COOH, mercapto, C,~-alkylmercapto, an optionally substituted C,_~o-alkyl, an optionally substituted C2_~o-alkenyl, an optionally substituted C2_~o-alkynyl, an optionally substituted C3_$-cycloalkyl, an optionally substituted C5_$-cycloalkanone, an optionally substituted Cøs-cycloalkenyl, an optionally substituted Cs_s-cycloalkynyl, an optionally substituted Cs_~o-aryl, an optionally substituted Cs-~o-aryl-C~-s-alkyl, Cs_~o-aryl-C2_s-alkenyl, Cs_~o-aryl-C2_s-alkynyl, an 90 optionally substituted C~-cycloalkyl-C~_s-alkyl, C~-cycloalkyl-C2_s-alkenyl or Cs_s-cycloalkyl-C2_s-alkynyl;
Rs denotes an optionally substituted 5-, 6- or 7-membered heterocyclic group which contains as heteroatom one or more atoms selected from the group comprising nitrogen, oxygen or sulphur, wherein the nitrogen may optionally be substituted and the heterocyclic group may be linked via a carbon atom or N-atom directly or via a C~_s-alkyl, C2_s-alkenyl or C2~-alkynyl bridge;
2o Rs denotes an optionally substituted C~_~o-alkylsulphonyl, C2_~o-alkenylsulphonyl or Cz_~o-alkynylsulphonyl, an optionally substituted C3_$-cycloalkylsulphonyl, an optionally substituted Cs-~o-arylsulphonyl, an optionally substituted Cs_~o-aryl-C~_s-alkylsulphonyl or an optionally substituted 25 heteroarylsulphonyl;
Rs denotes an optionally substituted C~_~o-alkylsulphonyloxy, C2_~o-alkenylsulphonyloxy or C2_~o-alkynylsulphonyloxy, an optionally substituted Cs_$-cycloalkylsulphonyloxy, an optionally substituted so Cs-~o-arylsulphonyloxy, an optionally substituted Cs_~o-aryl-C~_s-alkylsulphonyloxy or an optionally substituted heteroarylsulphonyloxy;
Rs denotes an optionally substituted C~_~o-alkylsulphonylamino, 35 C2_~o-alkenylsulphonylamino or C2_~o-alkynylsulphonylamino, an optionally substituted Cs~-cycloalkylsulphonylamino, an optionally substituted Cs-~o-arylsulphonylamino, an optionally substituted Cs_~o-aryl-C~_s-alkylsulphonylamino or an optionally substituted heteroarylsulphonylamino;

Rs denotes an optionally substituted C~-~o-alkylaminocarbonyl, C~_~o-dialkylaminocarbonyl, C~-~o-alkyl-CZ_~o-alkenylaminocarbonyl, C2_~o-alkenylaminocarbonyl, C2_~o-dialkenylaminocarbonyl, C2_~o-alkynylaminocarbonyl or C~_~o-alkyl-C2_~o-alkynylaminocarbonyl, an optionally substituted C3_$-cycloalkylaminocarbonyl, an optionally substituted Cs_~o-arylaminocarbonyl, an optionally substituted Cs_~o-aryl-C~_s-alkylaminocarbonyl or an optionally substituted heteroarylaminocarbonyl;
~o Rs denotes an optionally substituted C~_~o-alkylaminocarbonylamino, C2_~o-alkenylaminocarbonylamino or C2_~o-alkynylaminocarbonylamino, an optionally substituted C3~-cycloalkylaminocarbonylamino, an 95 optionally substituted Cs_~o-arylaminocarbonylar~ino, an optionally substituted C~~o-aryl-C~~-alkylaminocarbonylamino or an optionally substituted heteroarylaminocarbonylamino;
Rs denotes an optionally substituted C~_~o-alkyloxycarbonylamino, 2o C2_~o-alkenyloxycarbonylamino or C2_~o-alkynyloxycarbonylamino, an optionally substituted C3_$-cycloalkylcarbonylamino, an optionally substituted Cs_~o-aryloxycarbonylamino, an optionally substituted Cs_~o-aryl-C~_s-alkyloxycarbonylamino or an optionally substituted heteroaryloxycarbonylamino;
Rs denotes an optionally substituted C~_~o-alkylaminocarbonyloxy, C2_~o-alkenylaminocarbonyloxy or C2_~o-alkynylaminocarbonyloxy, an optionally substituted C3_s-cycloalkylaminocarbonyloxy, an optionally substituted Cs_~o-arylaminocarbonyloxy, an optionally substituted Cs_~o-aryl-C~_s-alkylaminocarbonyloxy or an optionally substituted heteroarylaminocarbonyloxy;
Rs denotes an optionally substituted C~_~o-alkyl-N-amidino, C2_~o-alkenyl-N-amidino or C2_~o-alkynyl-N-amidino, an optionally s5 substituted Cs_$-cycloalkyl-N-amidino, an optionally substituted Cs-~o-aryl-N-amidino, an optionally substituted Cs-~o-aryl-C~_s-alkyl-N-amidino or an optionally substituted heteroaryl-N-amidino;

Rs denotes an optionally substituted C~_~o-alkyloxy, C2_~o-alkenyloxy or C2_~o-alkynyloxy, an optionally substituted Cs-a-cycloalkyloxy, an optionally substituted Cs_~o-aryloxy, an optionally substituted Cs-~o-aryl-C~_s-alkyloxy or an optionally substituted heteroaryloxy;
Rs denotes an optionally substituted C~_~o-alkylcarbonyl, an optionally substituted C2_~o-alkenylcarbonyl, an optionally substituted C2_~o-alkynylcarbonyl, an optionally substituted Cs_s-cycloalkylcarbonyl, o an optionally substituted Cs_~o-arylcarbonyl, an optionally substituted Cs_~o-aryl-C~_s-alkylcarbonyl;
Rs denotes a group A-CO- wherein A is as hereinbefore defined;
5 Rs denotes an optionally substituted C~_~o-alkyloxycarbonyl, C2_~o-alkenyloxycarbonyl or C2_~o-alkynyloxycarbonyl, an optionally substituted Cs-s-cycloalkyloxycarbonyl, an optionally substituted Cs-~ o-aryloxycarbonyl, an optionally substituted Cs-~o-arYl-C~-salkyloxycarbonyl or an optionally substituted 2o heteroaryloxycarbonyl;
Rs denotes an optionally substituted C~_~o-alkylcarbonyloxy, C2_~o-alkenylcarbonyloxy or C2_~o-alkynylcarbonyloxy, an optionally substituted Cs_&-cycloalkylcarbonyloxy, an optionally substituted 25 Cs-~ o-arylcarbonyloxy, an optionally substituted Cs_~o-aryl-C~-salkylcarbonyloxy or an optionally substituted heteroarylcarbonyloxy;
Rs denotes an optionally substituted C~_~o-alkylthio, C2-~o-alkenylthio or C2_~o-alkynylthio, an optionally substituted Cs_$-cycloalkylthio, an optionally substituted Cs_~o-arylthio, an optionally substituted Cs_~o-aryl-C~-s-alkylthio or an optionally substituted heteroarylthio;
Rs denotes an optionally substituted C~_~o-alkylcarbonyloxy-C1_s-alkyl, 35 C2-~o-alkenylcarbonyloxy-C~_s-alkyl or C2_~o-alkynylcarbonyloxy-C~_s-alkyl, an optionally substituted Cs_8-cycloalkylcarbonyloxy-C~_s-alkyl, an optionally substituted Cs-~o-arylcarbonyloxy-C,-s-alkyl, Cs_,o-aryl-C~_s-alkylcarbonyloxy-C~-s-alkyl or heteroarylcarbonyloxy-C~_s-alkyl;

° 25771-646(S) R6 denotes an optionally substituted group of the formula R'-°0-B-(CH2)~
wherein n=1, 2, 3 or 4, where 8 denotes a C~.,o-aryl or a single bond;
Rg denotes an optionally substituted amine, preferably NRBR°;
~o R8 denotes an optionally substituted group of the formula 0 i o (CH2),~ \ I i I ~ ;
i ~s R6 denotes an optionally substituted group of the formula (CH2),.Z (CH2),.z (CHz),.a Y _Y ~ Y.~..
(CHZ),.2 (CHZ)~.z Y Y
C ~'Cs-Alkyl 2o wherein Y is a single bond or an alkylene, an alkenyiene or an alkynylene having up to 6, preferably 4 carbon atoms in the chain; or 25771-646 ( S J ~ 02242097 2002-O1-25 R6 is an optionally substituted group of the formula -Y , CH2)o.,.z -Y ' (CH2~0,1,2 (CH2~o.~,2 w w (CH2)°,,,2 i ~Y ( i Y
(CH2)o,,.2 wherein Y is a single bond or an alkylene, an alkenylene or an alkynylene having up to 6, preferably 4 carbon atoms in the chain;
R8 denotes hydrogen, an optionally substituted C3.s-cycloalkyl group, a branched or unbranched alkyl, aikenyl or alkynyl group having up to 10 carbon atoms, preferably an alkyl group having 1 to 4 carbon atoms which may optionally be substituted by hydroxy, phenyl, substituted phenyl, benzyl, substituted benzyl, amino, substituted amino, C,.B-, preferably C,.a-alkyloxy, or -(CHZ)m-NHCOOR'° wherein m =
1, 2, ~5 3 or 4;
R$ denotes a 5-, 6- or 7-membered heterocyclic group which is carbon linked directly or via a C,.a-alkyl chain and which contains one or more heteroatoms selected from the group comprising nitrogen, oxygen or 2p sulphur and may optionally be mono- or polysubstituted, preferably monosubstituted, by benzyl, optionally substituted benzyl, C,~-alkyl, halogen, -OR'°, -CN, -N02, NH2, -OH, =0, -COOH, -SOsH or -COOK'°;
or R8 denotes a bicyclic heterocyclic group which is C-linked directly or via a 25 C,~-alkyl chain and which contains one or more heteroatoms selected from the group comprising nitrogen, oxygen or sulphur and is optionally mono- or polysubstituted, preferably monosubstituted, by benzyl, optionally substituted benzyl, C,.a-alkyl, halogen, -OR'°, -CN, -N02, -NH2, -OH, =0, -COOH, -S03H, -COOK'°;
R9 denotes hydrogen, an optionally substituted C~.s-cycloalkyl group, a branched or unbranched alkyl, alkenyl or alkynyl group having up to 10, preferably 1 to 4 carbon atoms, which may optionally be substituted by 25771-646 (S) hydroxy, phenyl, substituted phenyl, benzyl, substituted benzyl, amino, substituted amino, C,~-, preferably C,~s-alkoxy, or -(CH2)m-NHCOOR'° wherein m equals 1, 2, 3 or 4;
R9 denotes a 5-, 6- or 7-membered heterocyclic group which is carbon linked directly or via a C~.a-alkyl chain and which contains one or more heteroatoms selected from the group comprising nitrogen, oxygen or sulphur and may optionally be mono- or polysubstituted, preferably monosubstituted, by benzyl, optionally substituted benzyl, C,.a-alkyl, o halogen, -OR'°, -CN, -N02, NHZ, -0H, =0, -COOH, -S03H or -COOR'°;
or R9 denotes a bicyclic heterocyclic group which is carbon linked directly or via a C,~-alkyl chain and which contains one or more heteroatoms selected from the group comprising nitrogen, oxygen or sulphur and may optionally be mono- or polysubstituted, preferably monosubstituted, by benzyl, optionally substituted benzyl, C,.~-alkyl, halogen, -OR'°, -CN, -N02, -NH2, -OH, =0, -COOH, -S03H, -COOR'°;
Of R8 and R9 together with the nitrogen atom form a saturated or 2o unsaturated 5- or 6-membered ring which may contain as further heteroatoms nitrogen, oxygen or sulphur, whilst the heterocyclic group may be substituted by a branched or unbranched alkyl group having 1 to 4 carbon atoms, preferably methyl, or may carry one of the following groups -(CH2)~-phenyl, -(CH2)~-NH2, =0, a ketal - preferably -0-CHI-CH2-0-, -(CHZ)nNH-C~.4-alkyl, -(CH2)n-N(Ct-s-alkyl)z~
-(CH2)~-NHCOOR'°, (n = 2, 3, 4), halogen, -OR'°, -CN, -N02, -NH2, -CH2NR8R9, -OH, -COOH, -SOsH, -COOR'°, -CONRaR9, -S02-R'°; and R'° denotes hydrogen C,~-alkyl, C2.a-alkenyl, C2.a-alkynyl, a benzyl or 3s phenyl group which is optionally mono- or polysubstituted by OCHs, optionally in the form of the racemates, the enantiomers and diastereomers thereof and their mixtures, as well as optionally the pharmacologically acceptable acid addition salts thereof.

25771-646(S) It will be appreciated that the dotted lines linking pairs of nitrogen atoms in formula (I) indicate the presence of a double bond in one of two alternative positions, such that both of R1 and R3, or of R4 and RS are not simultaneously present.
The compounds of general formula (I) form the following isomers:
O R~ O

R\ N R\ N
1 o N ~ R2 N I ~ R2 ~N N ~N N
N _N N _N ~R3 Rs Rs (Ia) (Ib) O O
R~
N N N N\ R2 ~I R R~ ~ N N
R~ ' \N N N
N i - N Rs -N
Rs Rs (Ic) (Id) the isomers of general formulae (Ia) and (Ib) being preferred, particularly those wherein R1 or R3 denotes hydrogen or C1_4-alkyl. Compounds of general formula (Ia) and (Ib) wherein R1 and R3 denote hydrogen are particularly preferred; in this case isomers (Ia) and (Ib) are tautomers.

25771-646(S) 14a According to one aspect of the present invention, there is provided a compound of any one of general formulae ( Ia) to ( Id) O R~ O
R\ N R\ N
N ~R2 N ~R2 \N N \N N
N _ N N N ~Ra s Rs R
(Ia) (Ib) O R~ O
N N R2 N N~ R2 5 ,~I 5 \
R~ ~N N R~ N N
N _N N _N ~R3 Rs Rs (Ic) (Id) wherein R1 or R3 denotes hydrogen, Cl_4-alkyl or benzyl; RZ
denotes hydrogen, or C1_e-alkyl; phenyl which is optionally substituted by any of halogen, C1_4-alkyl, C1_4-alkyloxy, hydroxy and NR8R9; phenyl-C1_6-alkyl, phenyl-C2_6-alkenyl or phenyl-Cz_6-alkynyl, wherein the phenyl ring is optionally substituted by any of halogen, C1_4-alkyl, C1_4-alkyloxy, hydroxy and NR8R9; an amine of formula NRBR9; a 5- or 6-membered heterocyclic group which is optionally C- or N-linked either directly or via a C1_4-alkylene bridge, containing one or more heteroatoms selected from the group comprising nitrogen and oxygen and optionally substituted by benzyl or C1_4-alkyl; a C3_6-cycloalkyl which is optionally substituted by any of =O, hydroxy, C1_4-alkyl and 25771-646(S) 14b Cl_4-alkyloxy; or any one of norbornane, norbornene, adamantane and noradamantane, optionally substituted by C1_4-alkyl; R4 or RS denotes, C1_e-alkyl, phenyl-C1_4-alkyl, phenyl-C2_6-alkenyl or phenyl-C2_6-alkynyl, wherein the phenyl ring is optionally substituted by any of halogen, hydroxy, C1_4-alkyl, Cl_4-alkyloxy and NReR9; R6 denotes hydrogen, or C1_8-alkyl, wherein the alkyl is optionally substituted by any of halogen, hydroxy, =O, C1_4-alkyloxy, NR8R9, phenyloxy, -0-phenyl-C1_4-alkyloxy, benzyloxy, -O-benzyl-O-C1_4-alkyloxy, -OCO-C1_4-alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-Cz_4-alkylene, -CO-C1_4-alkyl, -CHO, =NOH, -COON, -COO-C1_4-alkyl, -COO-phenyl, -COO-benzyl, -CONR8R9, -NHCO-Cl_4-alkyl, -NHCO-phenyl, -CO-Cl_4-alkyl-NReR9, -S020H, -S02-C1_4-alkyl or -S02-phenyl; phenyl which is optionally substituted by any of halogen, hydroxy, Cl_4-alkyl, C1_4-alkyloxy, benzyloxy, phenyloxy, -NReR9, -OCO-C1_4-alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-Cz_4-alkylene, -CO-C1_4-alkyl, -C1_4-alkyl-NH2, -C1_4-alkyl-OH, -C1_4-alkyl=NOH, -COOH, -COO-C1_4-alkyl, -COO-phenyl, -COO-benzyl, -CONReR9, -CO-C1_4-alkyl-NH2, -SOZOH, -SOZ-C1_4-alkyl and -SOZ-phenyl; phenyl-C1_4-alkyl, phenyl-CZ_6-alkenyl or phenyl-Cz_6-alkynyl, wherein the phenyl ring is optionally substituted by any of halogen, hydroxy, C,,_4-alkyl, Cl_4-alkoxy, benzyloxy, phenyloxy, -NR8R9, -OCO-C1_4-alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-Cz_4-alkylene, -CO-C1_4-alkyl, -C1_4-alkyl-NR8R9, -C1_4-alkyl-OH, -Cl_4-alkyl=NOH, -COOH, -COO-Cl_4-alkyl, -C00-phenyl, -COO-benzyl, -CONR8R9, -CO-C1_4-alkyl-NH2, -SOZOH, -S02-Cl_4-alkyl and -S02-phenyl; a 5- or 6-membered heterocyclic group optionally C- or N- linked either directly or via a C1_4-alkylene bridge, which contains one, two or three heteroatoms selected from nitrogen and oxygen and is optionally mono- or polysubstituted by benzyl or C1_4-alkyl; a C3_6-cycloalkyl or C3_6-cycloalkyl-Cl_4-alkyl 25771-646(S) 14c group which is optionally substituted by any of =0, hydroxy, C1_4-alkyl and C1_4-alkyloxy; any one of norbornyl, norbornenyl, adamantyl and noradamantyl optionally substituted by C1_4-alkyl; any one of -CHO, -COON, -COO-C1_4-alkyl, -COO-phenyl, -COO-benzyl and -CONR$R9; or an amine of general formula NReR9; Re denotes hydrogen, or a branched or unbranched C,,_4-alkyl group; or a C-linked 5- or 6-membered heterocyclic group which contains one, two or l0 three heteroatoms selected from the group comprising nitrogen, oxygen and sulphur and is optionally substituted by any of benzyl, C1_4-alkyl, C1_4-alkyloxy, halogen, -CN, -NO2, -NHZ, -OH and =O; and R9 denotes hydrogen, or a branched or unbranched C1_4-alkyl group; or a C-linked 5- or 6-membered heterocyclic group which contains one, two or three heteroatoms selected from the group comprising nitrogen, oxygen or sulphur and is optionally substituted by any of benzyl, C,,_4-alkyl, C1_4-alkyloxy, halogen, -CN, -NOZ, -NH2, -OH and =O; or RB and R9 together with the nitrogen atom in NRaR9 form a saturated or unsaturated 5- or 6-membered ring optionally substituted by a branched or unbranched C1_4-alkyl group, or by a - (CHZ) 1-4-Phenyl group; or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.
According to another aspect of the present invention, there is provided a compound of general formula (Ia) or (Ib) 25771-646(S) 14d O ~ O
R

R\ N N R~ N
R2 N ~ R2 N~ N N /\N N
-N N _N ERs s R Rs (Ia) (Ib) wherein Rl or R3 denotes hydrogen, C1_4-alkyl or benzyl; R2 denotes hydrogen, C1_6-alkyl, cyclopentyl, cyclohexyl, cyclopentanone, cyclohexanone, hydroxycylopentane or hydrocyclohexane; a morpholine group optionally substituted by C1_4-alkyl; a piperidinyl group; a piperazinyl group optionally substituted by benzyl or C1_4-alkyl; pyridyl;
tetrahydrofuranyl; tetrahydropyranyl; furyl; a phenyl group optionally substituted by any of C1_4-alkyl, halogen and hydroxy; a phenyl-C1_4-alkyl, wherein the phenyl ring is optionally substituted by any of halogen, C1_4-alkyl, C1_4-alkyloxy, hydroxy and NR8R9; an amine of general formula NR8R9; or norbornenyl, norbornyl, adamantyl or noradamantyl optionally substituted by C1_4-alkyl; R4 denotes C1_7-alkyl, or phenyl-C1_3-alkyl, wherein the phenyl ring is optionally substituted by any of halogen, hydroxy, C1_4-alkyl, C1_9-alkyloxy and NReR9; R6 denotes hydrogen, or C1_6-alkyl wherein the alkyl chain is optionally substituted by any of halogen, hydroxy, =O, C1_4-alkyloxy, NR8R9, phenyloxy, -O-phenyl-O-C1_4-alkyloxy, benzyloxy, -O-benzyl-0-C1_4-alkyloxy, -OCO-C1_4-alkyl, -OCO-phenyl, -OCO-pyridyl, -OCO-benzyl, -O-CZ_4-alkylene, -CO-C1_4-alkyl, -CHO, =NOH, -COOH, -COO-Cl_4-alkyl, -COO-phenyl, -C00-benzyl, -CONR8R9, -NHCO-C1_4-alkyl, -NHCO-phenyl, -CO-C1_4-alkyl-NRaR9, -SOZOH, -SOz-C1_4-alkyl and -SOZ-phenyl; phenyl, optionally 25771-646(S) 14e substituted by any of halogen, hydroxy, C1_4-alkyl, C1_4-alkyloxy and NR8R9; phenyl-C1_3-alkyl, wherein the phenyl ring is optionally substituted by any of halogen, hydroxy, C1_4-alkyl, C1_4-alkyloxy, benzyloxy, phenyloxy, -NReR9, -OCO-Cl_4-alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-CZ_4-alkylene, -CO-C1_4-alkyl, -C1_4-alkyl-NRBR9, -C1_4-alkyl-OH, -C1_4-alkyl=NOH, -COOH, -COO-C1_4-alkyl, -COO-phenyl, -COO-benzyl, -CONRBR9, -CO-C1_4-alkyl-NR8R9, -S02oH, -S02-Cl_4-alkyl and -S02-phenyl; any of cyclopentyl, cyclohexyl, cyclohexyl-C1_3-alkyl, cyclopentanone, cyclohexanone, hydroxycyclopentane and hydroxycyclohexane linked to the rest of the compound via a single bond or via a C1_4-alkylene chain; any one of furan, tetrahydrofuran, a-pyran, Y-pyran, dioxolane, tetrahydropyran, dioxane, thiophene, thiolane, dithiolane, pyrrole, pyrroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, morpholine, thiomorpholine, oxazole, isoxazole, oxazine, thiazole, isothiazole, thiadiazole, oxadiazole and pyrazolidine linked to the rest of the compound via a single bond or via a Cl_4-alkylene chain; any one of -CHO, -COOH, -COO-C1_4-alkyl, -COO-phenyl, -COO-benzyl, -CO-NH-C1_4-alkyl, -CO-N(C1_4-alkyl)z and -CO-NH-phenyl; or an amine of general formula NR8R9; R8 denotes hydrogen, or a branched or unbranched C1_4-alkyl group; or any one of a C-linked pyrrole, pyrroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, morpholine, oxazole, isoxazole, thiazole, isothiazole and thiadiazole optionally substituted by any of chlorine, bromine, C1_4-alkyl, C1_4-alkyloxy, -NO2, -NH2 and -OH; and R9 denotes hydrogen, a branched or unbranched C1_4-alkyl group; or any one of a C-linked pyrrole, pyrroline, pyrrolidine, pyrazole, 25771-646 (S) 14f pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, morpholine, oxazole, isoxazole, thiazole, isothiazole and thiadiazole optionally substituted by any of chlorine, bromine, C1_4-alkyl, C1_4-alkyloxy, -NO2, -NH2, and -OH; or R8 and R9 together with the nitrogen atom in NReR9 form a saturated or unsaturated 5- or 6-membered ring optionally substituted by a branched or unbranched C1_4-alkyl l0 group, or by a -(CHZ)1-4-phenyl group; or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.
According to still another aspect of the present invention, there is provided a compound of general formula (Ib) O

\ N N~ R2 Ni N N
~R3 Rs (Ib) wherein RZ denotes hydrogen, C1_4-alkyl, phenyl, or benzyl, wherein the phenyl ring of the benzyl is optionally fluorine-substituted, pyridyl, piperidinyl, morpholinyl, piperazinyl, 4-benzylpiperazinyl, furyl, tetrahydrofuranyl, tetrahydropyranyl, NR8R9, cyclopentyl, cyclohexyl, adamantyl, noradamantyl, norbornyl or norbornenyl; R3 denotes hydrogen, Cl_3-alkyl or benzyl; R4 denotes Cl_5-alkyl or benzyl; R6 denotes hydrogen, Cl_4-alkyl; Cl_4-alkyl optionally 25771-646(S) 14g substituted by any of OH, chlorine, bromine, Cl_4-alkyloxy and NR8R9; -CHO, -COOH, -COO-C1_4-alkyl, phenyl, phenyl-Cl_3-alkyl optionally substituted by fluorine or benzyloxy, optionally methoxy-substituted phenyloxy-C1_3-alkyl, optionally methoxy-substituted benzyloxy-C1_3-alkyl, benzyloxybenzyl, benzoyloxymethyl, pyridylcarbonyloxymethyl, cyclopentyl, furyl, cyclohexylmethyl, pyridylmethyl, N-pyrrolylmethyl or l0 N-morpholinomethyl; Re denotes hydrogen, Cl_4-alkyl or pyridyl; and R9 denotes hydrogen, C1_4-alkyl or pyridyl; or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.
According to yet another aspect of the present invention, there is provided a compound of general formula (Ia) R~
RAN N

Ni N N
I
~N
R /s (Ia) wherein R1 denotes hydrogen, Cl_3-alkyl or benzyl; RZ denotes hydrogen, C1_4-alkyl, phenyl, benzyl, wherein the phenyl ring of the benzyl is optionally fluorine-substituted, pyridyl, piperidinyl, morpholinyl, piperazinyl, 4-benzylpiperazinyl, furyl, tetrahydrofuranyl, tetrahydropyranyl, NR8R9, cyclopentyl, cyclohexyl, adamantyl, noradamantyl, norbornyl or norbornenyl; R4 denotes C1_5-alkyl or benzyl; R6 denotes 25771-646(S) 14h hydrogen, C1_4-alkyl optionally substituted by any of OH, chlorine, bromine, C1_4-alkyloxy and NRBR9, -CHO, -COON, -C00-C1_4-alkyl, phenyl, phenyl-C1_3-alkyl optionally substituted by fluorine or benzyloxy, optionally methoxy-substituted phenyloxy-C1_3-alkyl, optionally methoxy-substituted benzyloxy-C1_3-alkyl, benzyloxybenzyl, benzoyloxymethyl, pyridylcarbonyloxymethyl, cyclopentyl, furyl, cyclohexylmethyl, pyridylmethyl, N-pyrrolylmethyl or N-morpholinomethyl; Re denotes hydrogen, Cl_4-alkyl or pyridyl; and R9 denotes hydrogen, C1_4-alkyl or pyridyl; or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.
According to a further aspect of the present invention, there is provided a compound of general formula (IC) O
R
N

Rs / \N N
N
~N
R ~s (Ic) wherein R1 denotes hydrogen or C1_3-alkyl; RZ denotes hydrogen, C1_4-alkyl, cyclopentyl, cyclopentanone, hydroxycyclopentane, furan or benzyl; R5 denotes C1_6-alkyl;
and R6 denotes hydrogen, benzyl or cyclopentyl; or a racemate enantiomer or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or i ~~~ ; a 25771-646(S) 14i a pharmacologically acceptable acid addition salt of the compound.
According to yet a further aspect of the present invention, there is provided a compound of general formula (Id) O
N N

RAN N N
- N ~R3 Rs (Id) wherein R3 denotes hydrogen or C1_3-alkyl; R2 denotes hydrogen, C1_4-alkyl, cyclopentyl, cyclopentanone, hydroxycyclopentane, furan or benzyl; RS denotes C1_6-alkyl;
and R6 denotes hydrogen, benzyl or cyclopentyl; or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.
According to still a further aspect of the present invention, there is provided a compound of general formula (Ib) O

~N N

N~ N N
N ERs Rs (Ib) 25771-646(S) 14j wherein RZ denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 2-furyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMe2, cyclopentyl, cyclohexyl, adamantan-1-yl, noradmantan-3-yl, norbornan-2-yl or 5-norbornen-2-yl; R3 denotes hydrogen, methyl, ethyl, n-propyl or benzyl; R4 denotes methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, n-pentyl or benzyl; and R6 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl)-NH-CHZ-, Ph-CO-O-CH2-, pyridyl-CO-0-CHZ-, Ph-0-CHZ-, (4-Me0-Ph) -O-CH2-, (4-Me0-Ph) -CHZ-O-CHz-, (4-Ph-CH2-O-Ph) -CH2-, 4-F-Ph-CHZ-, 3,4-F-Ph-CHz-, -COOH, -COOMe, -CHz-OH, -CHz-OMe, -CHZOEt or -CHZ-NMez; or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.
According to another aspect of the present invention, there is a compound of general formula (Ia) R~

R~ N N

Ni N N
~N
R /s (Ia) 25771-646(S) 14k wherein R1 denotes hydrogen, methyl, ethyl, n-propyl or benzyl; RZ denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 2-furyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMez, cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norbornan-2-yl or 5-norbornen-2-yl; R4 denotes methyl, ethyl, l0 n-propyl, i-propyl, n-butyl, tert.-butyl, n-pentyl or benzyl; and R6 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl)-NH-CH2-, Ph-CO-O-CHZ-, pyridyl-CO-O-CHZ-, Ph-0-CHz-, (4-Me0-Ph) -0-CHZ-, (4-Me0-Ph) -CHZ-O-CHz-, (4-Ph-CHZ-0-Ph) -CHz-, 4-F-Ph-CHZ-, 3,4-F-Ph-CH2-, -COOH, -COOMe, -CHZ-OH, -CHZ-OMe, -CHzOEt or -CHz-NMez; or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.
According to yet another aspect of the present invention, there is provided a compound of general formula (Ib) R\ N N~ 2 ~R
Ni N N
N ~R3 Rs (Ib) 25771-646(S) wherein R2 denotes hydrogen, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, 2-pyridyl, 3-pyridyl 4-pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMez, cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norbornan-2-yl or 5-norbornen-2-yl; R3 denotes hydrogen; R4 denotes methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, n-pentyl or l0 benzyl; and R6 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, 2-phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl)-NH-CH2-, Ph-C00-CHZ-, 3-pyridyl-COO-CHZ-Ph-O-CHz-, (4-Me0-Ph) -O-CH2-, (4-Me0-Ph)-CHZ-0-CHZ-, 4-F-Ph-CHz-, 3,4-F-Ph-CH2-, -CHZ-OH, -CHZ-OMe, -CH2-OEt, -CHz-NMe2, -COOMe or -COON; or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.
According to a further aspect of the present invention, there is provided a compound of general formula (Ia) O
R

2 5 R~ N N

Ni N N
I
~N
R /s (Ia) wherein R1 denotes hydrogen; RZ denotes hydrogen, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, N-piperidinyl, 25771-646(S) 14m N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 3-tetrahyydrofuranyl, 4-tetrahydropyranyl, -NMe2, cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norbornan-2-yl or 5-norbornen-2-yl; R4 denotes methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, n-pentyl or benzyl; and R6 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, 2-phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl)-NH-CHz-, Ph-C00-CH2-, 3-pyridyl-COO-CHZ-, Ph-0-CHZ-, (4-Me0-Ph) -OCH2-, (4-Me0-Ph)-CH2-O-CHZ, 4-F-Ph-CHZ-, 3,4-F-Ph-CHZ-, -CHZ-OH, -CHz-OMe, -CHZ-OEt, -CHz-NMez, -COOMe or -COOH; or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.
Preferred compounds are the compounds of general formulae (Ia) to (Id) wherein R1 or R3 denotes hydrogen, Cl_4-alkyl, benzyl, preferably hydrogen;
R2 denotes hydrogen, a C1_e-alkyl, Cz_e-alkenyl or CZ_8-alkynyl group which may optionally be substituted, by -CN, -CH2NR8R9, -OH
(polysubstitution also possible), -ORl°, -NR$R9, -NHCOR1°, -NHCONReR9, -NHCOOR1°, halogen, -OCORlo, -OCO-pyridyl, -OCHZCOOH, -OCH2COOR1°, -SOzR7, -S-R7, -NHCONH-phenyl, -OCHZ-CONR8R9, -OCHzCH20H, -S02-CH2-CH2-O-CORl°, -OCH2-CHz-NReR9, -S02-CHZ-CHZ-OH, -CONHSOzRl°, -CHZCONHSOZRlo, -OCH2CHZOR1°, -COOH, -COORl°, -CONR8R9, -CHO, -SRlo, -SORT°, -SOZRl°, -S03H, -S02NR8R9, -OCH2-CH20COR'°, -CH=NOH, -CH=NOR'°, =O, -COR", -CH(OH)R", -CH(OR'°)2, -CH=CH-R'2, OCONR$R9, optionally mono- or poly-substituted, preferably mono-methyl-substituted, 1,3-dioxolane or 1,3-5 dioxane;
R2 denotes phenyl-C~_s-alkyl, preferably phenyl-C~~-alkyl, phenyl-C2~-alkenyl or phenyl-C2_6-alkynyl, wherein the phenyl ring is optionally substituted either directly or via a C~~-alkylene bridge by one or more, o preferably one, of the groups -C~_3-alkyl, -CN, -NR$R9, -N02, -OH, -OR'°, -CH2-NH-S02-R'°, -NHCOR'°, -NHCONR$R9, halogen, -OCOR'°, -OCO-pyridyl, -OCH2COOH, -OCH2COOR'°, -CH20COR'°, -S02R7, -OCH2-CONR$R9, -OCHZCHZOH, -OCH2-CH2-NR$R9, -CONHS02R'°, -OCH2CH20R'°, -COOH, -COOR'°, -CF3, cyclopropyl, 15 -CONR$R9, -CH20H, -CHZOR'°, -CHO, -SR'°, -~iOR'°, -S02R'°, -S03H, -S02NR$R9, -OCH2-CH20COR'°, -CH=NOH, -CH=NOR'°, -COR", -CH(OH)R", -CH(OR'°)2, -NHCOOR'°, -CHZCONHS02R'o, -CH=CH-R'2, OCONR$R9, -CH2-O-CONR$R9, -CH2-CH2-O-CONR$R9, optionally mono- or poly- preferably mono-methyl-substituted 1,3-2o dioxolane or 1,3-dioxane;
R2 denotes Cs_~-cycloalkyl-C~_6-alkyl, Cs_~-cycloalkyl-C2_s-alkenyl, C3_~-cycloalkyl-C2_6-alkynyl, wherein the cycloalkyl group is optionally substituted either directly or via a C~_4-alkylene bridge by one or more, preferably one, of the groups -CN, NR$R9, =O, -OH, -OR'°, -NR$R9, -NHCOR'°, -NHCONR$R9, halogen, -OCOR'°, -OCO-pyridyl, -OCH2COOH, -OCH2COOR'°, -CH20COR'°, -SOZR7, -OCH2-CONR$R9, -OCH2CH20H, -OCHZ-CH2-NR$R9, -OCH2CH2OR'°, -COOH, -COOK'°, -CONR$R9, -CH20H, -CH20R'°, -CHO, -SR'o, -SOR'°, -S02R'°, -SOsH, -S02NR$R9, -OCH2-CH20COR'°, -CH=NOH, -CH=NOR'°, -COR", -CH(OH)R", -CONHS02R'°, -CH(OR'°)2, -NHCOOR'°, -CH=CH-R'2, -OCONR$R9, -CH2-O-CONR$R9, -CH2-CH2-O-CONR$R9, methyl-substituted 1,3-dioxolane or 1,3-dioxane;

25771-646(S) RZ denotes a group of the formula A-C,-s-alkyl, A-CONH-C,$-alkyl, A-CONH-CZ.e-alkenyi, A-CONH-C2~-alkynyl, A-NH-CO-C,.a-alkyl, A-NH-CO-CZ.s-alkenyi, A-NH-CO-CZ$-alkynyl, A-C2$-alkenylene, A-C2~-alkynylene or A-, wherein A is a C- or N-linked 5-, 6- a 7-membered heterocydic group which contains ~e or more heteroatpms from the group comprising nitrogen, oxygen or sulphur and may optionally be mono- or poly-, preferably monosubstituted by benzyi, optionally substituted benzyl, C,~-alkyl, halogen, -OR'°, -CN, -NOz -NHI, -CHZNRBR°, -OH, =O, a io ketal, ethyleneketai, -COOH, -SO~H, -COOR'°, -CONaR9, -COR", -SOrR'° or -CONR8R9;
RZ denotes C~.rcyctoalkyl, preferably cydopentyi or cydohexyl, which may optionally be substituted by =O, -OH, -0R'°, OCOR'° or -OCO-pyridyl;
RZ denotes phenyl which is optionally substituted by -OH, halogen, -0R'°, 15 C,.e-alkyl, preferably -CHI, -NH2, -COOH, -SO~H, -COOK'°, -OCHZCOOR'°, -CN or -OCH2CONR"R9;
RZ denotes a norbomane, norbornene, C~.s-dicycloalkylmethyl, preferably dicyciopropyimethyl, adamantane or noradamatane group optionally substituted by Cm-alkyi, preferably methyl;
20 RZ denotes -CH=CH-phenyl in which the phenyl ring is mono- or polysubstituted by methoxy, hydroxy or halogen;
RZ is a (3.3.OJ-bicyclooctane, preferably a [3.3.OJ-bicyclooctan-2-yl;
RZ is a C-linked piperidine or furan; or RZ is an amine of general formula NRaR9;
25 R~ Or Rs denotes, an optionally branched C1_,-alkyl, C~_,-alkenylor C1-0-alkynyl group which may optiona~yy be substituted by -CN, -CHZNReR9, -OH (polysubstitution also possible), -OR'°, -NR°R9, -NHCOR'°, -NHCONR°R9, halogen, -OCOR'°, -OCO-pyridyl, 25771-646(S) -OCHZCOOH, -OCH2COOR'°, -SOzR', -S-R', -NHCONH-phenyl, -OCH2-CONR$R~, -OCH2CH20H, -SOZ-CH2-CH2-O-COR'°, -OCH2-CH2-NReR~, -SOrCH2-CHZ-OH, -CONHS02R'°, -CH2CONHS02R'°, -OCH2CH20R'°, -COOH, -COOR'°, -CONRBR~, -CHO, -SR'°, -SOR'°, -S02R'°, -S03H, -S02NR8R9, -OCH2-CH20COR'°, =0, -CH=NOH, -CH=NOR'°, -COR", -CH(OH)R", -CH(OR'°)2, -CH=CH-R'2, -OCONR8R9, optionally mono- or poly-, preferably mono-methyl-substituted 1,3-dioxolane or 1,3-dioxane;
~o R4 or RS denotes phenyl-C,.~-alkyl, preferably phenyl-C,~-alkyl, phenyl-C2~-alkenyi or phenyl-C2~-alkynyl, wherein the phenyl ring is optionally substituted either directly or via a C,.a-alkylene bridge by one or more, preferably one of the groups, C,_3-alkyl, -CN, -NRaR9, -N02, r5 -OH, -OR'°, -CH2-NH-SOrR'°, -NHCOR'°, -NHCONR8R9, halogen, -OCOR'°, -OCO-pyridyl, -OCH2COOH, -OCH2COOR'°, -CH20COR'°, -S02R', -OCH2-CONReR9, -OCH2CH20H, -OCHZ-CH2-NRaR9, -CONHS02R'°, -OCHZCH20R'°, -COOH, -COOR'°, -CF3, cyciopropyl.
-CONRaR9, -CHZOH, -CH20R'°, -CHO, -SR'°, -SOR'°, -SOzR'°, -SOsH, 20 -SOZNRaR~, -OCH2-CH20COR'°. -CH=NOH, -CH=NOR'°, -COR", -CH(OH)R", -CH(OR'°)2, -NHCOOR'°, -CHZCONHS02R'°, -CH=CH-R'2, -OCONR8R9, -CH2-0-CONRaR~, -CH2-CH2-0-CONRaR9, optionally mono- or poly-, preferably mono-methyl-substituted 1,3-dioxolane or 1,3-dioxane;
R4 or RS denotes an optionally substituted C~rcycioalkyi group;
R4 or R5 denotes C3-~-cycloalkyl-C,.s-alkyl, C3.~-cycloalkyl-C2.~-aikenyl, C3_~-cycloalkyl-CZ.s-alkynyl, wherein the cycloalkyl group is optionally 3o substituted either directly or via a C,.~-alkylene bridge by -CN, -NR8R9, =0, -OH, -OR'°, -NReR9, -NHCOR'°, -NHCONR8R9, halogen, -OCOR'°, -OCO-pyridyl, -OCH2COOH, -OCH2COOR'°, -CH20COR'°, -S02R', -OCH2-CONR$R9, -OCH2CH20H, -OCH2-CH2-NR$R9, -OCHzCH20R'°, -COOH, -COOR'°, -CONR8R9, -CHZOH, -CH20R'°, -CHO, -SR'°, -SOR'°, -S02R'°, -S03H, -SO~NRaR9, -OCH2-CH20COR'°, -CH=NOH, -CH=NOR'°, -COR", -CH(OH)R", -CONHS02R'°, -CH(OR'°)2, -NHCOOR'°, -CH=CH-R'2, -OCONR8R9, -CH2-0-CONR8R3.
-CHI-CHI-O-CONRaR9, optionally mono- or poly-, preferably mono-methyl-substituted 1,3-dioxolane or 1,3-dioxane: or R4 or RS denotes a group of the formula A-C,_s-alkyl, A-CONH-C,_s-alkyl, A-CONH-Cz_s-alkenyl, A-CONH-Cz_s-alkynyl, A-NH-CO-C,_s-alkyl, A-NH-CO-Cz~-alkenyl, A-NH-CO-Cz_s-alkynyl, A-C2_s-alkenyl or A-CZ_s-alkynyl, wherein A is a C- or N-linked heterocyclic group which contains one or more heteroatoms selected from the group comprising nitrogen, oxygen or sulphur and may optionally be mono- or polysubstituted, preferably o monosubstituted, by C,~-alkyl, halogen, -OR'°, -CN, -NOz, -NHz, -CHZNR$R9, -OH, =O, a ketal, ethyleneketal, -COOH, -SOsH, -COOR'o, -CONR$R9, -COR", -SOz-R'° or -CONR$R9;
Rs denotes hydrogen, a C,_$-alkyl, Cz_s-alkenyl or Cz_a-alkynyl group which ~5 may optionally be substituted by -CN, -CH2NR$R9, -OH (polysubstitution also possible), -OR'°, -NR$R9, -NHCOR'°, -NHCONR$R9, -NHCOOR'o, halogen, -OCOR'°, -OCO-pyridyl, -OCH2COOH, -OCH2COOR'o, -S02R7, -S-R7, -NHCONH-phenyl, -OCHz-CONR$R9, -OCHZCH20H, -SOz-CHz-CHz-O-COR'°, -OCHz-CHz-NR$R9, -SOz-CHz-CHz-OH, 20 -CONHS02R'°, -CH2CONHSOzR'°, -OCH2CHzOR'°, -COOH, -COOK'°, -CONR$R9, -CHO, -SR'°, -SOR'°, -SOzR'°, -SOsH, -S02NR$R9, -OCHz-CH20COR'°, -CH=NOH, -CH=NOR'°, -COR", -CH(OH)R", -CH(OR'°)z, -CH=CH-R'z, -OCONR$R9, optionally mono- or poly-, preferably mono-methyl-substituted 1,3-dioxolane or 1,3-dioxane;
Rs denotes phenyl-C,_s-alkyl, preferably phenyl-C,_4-alkyl, phenyl-Cz_s-alkenyl or phenyl-Cz_s-alkynyl, wherein the phenyl ring is optionally substituted either directly or via a C,_4-alkylene bridge by one or more of the groups, -C,_3-alkyl, -CN, -NR$R9, -NOz, -OH, -OR'°, -CHz-NH-SOz-R'°, -NHCOR'°, -NHCONR$R9, halogen, -OCOR'°, -OCO-pyridyl, -OCH2COOH, -OCH2COOR'°, -CH20COR'°, -SOzR7, -OCHz-CONR$R9, -OCH2CH20H, -OCHz-CHz-NR$R9, -CONHS02R'°, -OCH2CHzOR'°, -COOH, -COOR'°, -CF3, cyclopropyl, -CONR$R9, -CHZOH, -CH20R'°, -CHO, -SR'°, -SOR'°, -S02R'°, -SOsH, -S02NR$R9, -OCHz-CH20COR'°, -CH=NOH, -CH=NOR'°, -COR", -CH(OH)R", -CH(OR'°)z, -NHCOOR'°, -CH2CONHSOzR'°, -CH=CH-R'z, -OCONR$R9, -CHz-O-CONR$R9, -CHz-CHz-O-CONR8R9, -CO-R'°, -CO-C,_4-alkyl-NR$R9, optionally mono- or poly-, preferably mono-methyl-substituted 1,3-dioxolane or 1,3-dioxane;

Rs denotes C~~-cycloalkyl-C»-alkyl, Cs_~-cycloalkyl-C2_s-alkenyl, C3_7-cycloalkyl-C2_s-alkynyl, wherein the cycloalkyl group is optionally substituted either directly or via a C~_4-alkylene bridge by one or more, preferably one, of the groups -CN, NR8R9, =O, -OH, -OR'°, -NR$R9, -NHCOR'°, -NHCONR8R9, halogen, -OCOR'°, -OCO-pyridyl, -OCH2COOH, -OCH2COOR'°, -CH20COR'°, -S02R7, -OCH2-CONR$R9, -OCH2CH20H, -OCH2-CH2-NR$R9, -OCH2CH20R'°, -COOH, -COOR'°, -CONR$R9, -CH20H, -CH20R'°, -CHO, -SR'°, -SOR'°, -S02R'°, -SOaH, -S02NR$R9, -OCH2-CHZOCOR'°, -CH=NOH, -CH=NOR'°, -COR", -CH(OH)R", -CONHS02R'°, -CH(OR'°)2, -NHCOOR'°, -CH=CH-R'2, -OCONR$R9, -CH2-O-CONR$R9, -CH2-CH2-O-CONR$R9, methyl-substituted 1,3-dioxolane or 1,3-dioxane;
Rs denotes a group of the formula A-C~_s-alkyl, A-CONH-C~_s-alkyl, A-CONH-C2_s-alkenyl, A-CONH-C2_s-alkynyl, A-NH-CO-C1_s-alkyl, A-NH-CO-C2_s-alkenyl, 2o A-NH-CO-C2_s-alkynyl, A-C2~-alkenyl or A-C2_s-alkynyl or A-, wherein A is a C- or N-linked 5-, 6- or 7-membered heterocyclic group which contains one or more heteroatoms from the group comprising nitrogen, oxygen or sulphur and may optionally be mono- or polysubstituted, preferably monosubstituted, by benzyl optionally substituted benzyl, C~_4-alkyl, halogen, -OR'°, -CN, -N02, -NH2, -CH2NR$R9, -OH, =O, a ketal, ethyleneketal, -COOH, -SOsH, -COOR'°, -CONR$R9, -COR", -S02-R'° or -CONR$Rg;
Rs denotes -CHO, -COOR'°, -CONR$R9;
Rs denotes C3_7-cycloalkyl, preferably cyclopentyl or cyclohexyl, optionally substituted by =0, -OH, -OR'°, OCOR'° or -OCO-pyridyl;
Rs denotes phenyl optionally substituted by -OH, halogen, -OR'°, C~_4-alkyl, preferably -CH3, -NH2, -COOH, -SOsH, -COOR'o, -OCHZCOOR'°, -CN or -OCH2CONR$R9;

25771-646(S) R6 denotes a norbonane, norbornene, C3.s-dicycloalkylmethyl, preferably dicyGopropylmethyl, adamantine or noradamantane group optionally substituted by C,~-alkyl, preferably methyl;

Rg denotes -CH=CH-phenyl, wherein the phenyl ring may be mono- or poiysubstituted by methoxy, hydroxy or halogen;
Re denotes a [3.3.0]-bicycloociane, preferably a [3.3.0]-bicyclooctan-2-yl; or JO
RB denotes a C-linked piperidine or furan;
R~ denotes C,.~-alkyl which is.optionally substituted by -OH, -OCOR'°, -OCO-pyridyl, -NH2, -NReR~ or -NHCOR'°, preferably -CH2-CH2-OH.
J5 -CHZ-CH20COR'°, -CHrCH2-CH2-OH or -CHrCH2CH20COR'°;
R8 denotes hydrogen, an optionally substituted C~-cycloalkyl group, a branched or unbranched alkyl, alkenyl or alkynyl group having up to 10 carbon atoms, preferably a C,~-alkyl group which may optionally be Zo substituted by hydroxy, phenyl, substituted phenyl, benzyl, substituted benzyi, amino, substituted amino or C,.a-alkoxy, preferably C,~-aikoxy, or -(CH2)m-NHCOOR'° where m = 1, 2. 3 or 4;
Re denotes a 5-, 6- or 7-membered heterocycfic group which is C-linked directly or via a C,.~-alkyl chain, and which contains one or more heteroatoms selected from the group comprising nitrogen, oxygen or sulphur and may optionally be mono- or polysubstituted, preferably monosubstituted by benzyl, optionally substituted benzyl, C,.,-alkyl, halogen, -OR'°, -CN, -N02, -NHZ, -OH, =0, -COOH, -S03H or -COOR'°; or Re denotes a bicyciic heterocyclic group C-linked directly or via a C,~-alkyl chain, which contains one or more heteroatoms from the group comprising nitrogen, oxygen or sulphur and may optionally be mono- or polysubstituted, preferably monosubstituted by benzyl, optionally substituted benzyl, C,.~-alkyl, halogen, -OR'°, -CN, -N02, -NHZ, -OH, =0, -COOH, -SOaH or -COOR'°;

25771-646(S) R9 denotes hydrogen, an optionally substituted Ca.e-~ycloaikyl group, a branched or unbranched alkyl, alkenyl or alkynyi group having up to 10 carbon atoms, preferably a C,.~-alkyl group, which may optionally be substituted by hydroxy, phenyl, substituted phenyl, benzyi, substituted benzyl, amino, substituted amino or C,.B-alkoxy, preferably C,.~-alkoxy, or -(CHz)m-NHCOOR'° wherein m is 1, 2, 3 or 4, preferably hydrogen;
R° denotes a 5-, 6- or 7-membered heterocyclic group which is C-linked directly or via a C,.~-alkyl chain, and which contains one or more heteroatoms selected from the group comprising nitrogen, oxygen or sulphur and may optionally be mono- or polysubstituted, preferably monosubstituted by benzyi, optionally substituted benzyl, C,.~-alkyl, halogen. -OR'°, -CN, -NOz, -NHz, -OH, =0, -COOH, -SOaH or ~5 -COOR'°; or ' R9 denotes a bicyclic heterocyclic group C-linked directly or via a C,.~-alkyl chain, which contains one or more heteroatoms from the group comprising nitrogen, oxygen or sulphur and may optionally be mono- or 2o polysubstituted, preferably monosubstituted by benzyi, optionally substituted benzyl, C,~-alkyl, halogen, -OR'°, -CN, -NOz, -NHz, -OH, =O, -COOH, -S03H or -COOK'°, or R° and R9 together with the nitrogen atom farm a saturated or 25 unsaturated 5- or 6-membered ring which may contain nitrogen, oxygen or sulphur as additional heteroatoms, whilst the heterocyciic group may be substituted by a branched or unbranched C,.~-alkyl group, preferably methyl, or may carry one of the foilowirg groups:
30 -( C H Z)n-phenyl, -(CHZ)"-NHz, =0, a ketal - preferably -0-CHz-CHz-O-, -(CHz)"NH-C,.s-alkyl, -(CHZ)a-N(C,$-alkyl)z, -(CHZJ"-NHCOOR'°, (n = 1, 2, 3, 4), halogen, 35 -Ot~'°, -CN, -NOz, -NHz, -CHZNReR9, -OH, -COOH, -SOaH, -COOR'°, -CONK°R9, -SOz-R'°;
R'° denotes hydrogen, C,.e-alkyl, C2~-aikenyl, CZ~-alkynyl, a benzyl or phenyl group which is optionaNy mono- or polysubstituted by OCH3:

25771-646(S) R" denotes C,.a-alkyl, Cz-~-alkenyl, CZ.a-alkynyl, optionally substituted phenyl, optionally substituted benzyl, C3.s-cycioalkyl; and R'2 denotes -COOR'°, -CH20R'°, -CONR8R9, hydrogen, C,~-alkyl, optionally substituted phenyl or -CHZNReR9, optionally in the form of the racemates, enantiomers and diastereomers thereof and mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.
to Also preferred are compounds of general formula (la) to (Id) 0 Ri 0 RvN N Z RvN N
~~-- R I ~ . ~ R
N~N N NON N s N ~=-N R
RB (la) . Rg (Ib) 0 R, O
N
N
~~."- R2 ~ ~ y-' R2 R-,N~ N N R-,N N N 3 _N N R
B
Rs~ Id R ( Ic) ( ) wherein R' or R3 denotes hydrogen, C,.a-alkyl ar benzyi;
RZ denotes hydrogen, C,.B-alkyl, preferably C,$-alkyl;
R2 denotes phenyl which is optionally substituted by halogen, preferably fluorine or chlorine, C,.~-alkyl, C,.e-alkylaxy, hydroxy or NReR9;
R2 denotes phenyl-C,.B-alkyl, preferably benzyt, phenyl-C2.a-alkenyl or phenyl-CZ-s-alkynyi, wherein the phenyl ring is optionally substituted by halogen, preferably fluorine or chlorine, C,~-alkyl, C,~,-alkyloxy, hydroxy or NReR9;

25771-646(S) R= denotes an optionally substituted amine, preferably NR°R9;
R= denotes a 5- or 6-membered heterocydic group which is optionally C-or N-linked either directly or via a C,.,-alkylene bridge, containing one or more heteroatoms selected from the group comprising nitrogen or oxygen and optionally substituted by benzyl or C,.~-alkyl;
Ri denotes a C~cloalkyl which may optionally be substituted by =O, hydroxy, C,.~-alkyl or C,.,-alkyioxy;
Rs denotes norbomane, norbomene, adamantane or noradamantane optionally substituted by C,.~-alkyl, preferably methyl;
R4 or R° denotes,Cl.,-alkyl, phenyl-Cl_,-alkyl, preFerably benzyl, phenyl-Cz.a-alkenyt or phenyl- Ci.a-alkynyl, wherein the phenyl ring is optionally substituted by halogen, preferably chlorine or fluorine, hydroxy, C,.a-alkyl, C,~-atkyloxy or NRaR9;
R° denotes hydrogen, C,.e-alkyl, wherein the alkyl chain rnay be substituted by halogen, hydroxy, =0, C,.,s-alkyloxy, NR°R9, phenyloxy, -O-phenyl- C,~-alkyloxy, benzyioxy, -O-benzyl-0-C,.~-alkyloxy, -OCO-C,~-alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C=.,-alkylene, -CO- C,~-alkyl, -CHO, =NOH, -COOH, -COO-C,~-alkyl, -COO-phenyl, -COO-benzyl, -CONK°R°, -NHCO-C,.,-alkyl, -NHCO-phenyl, -CO-C,~-alkyl-NR°R9, -SO=OH, -SOZ-C,.,,-alkyl or -S02-phenyl;
R° denotes phenyl which may optionally be substituted by halogen, preferably chlorine or fluorine, hydroxy, C,.~-alkyl, C,.,-alkyloxy, benzyloxy, phenyloxy, NR°R°, -OCO-C,.s-alkyl, -OCO-phenyl, -OCO-benzyl, -0CO-pyridyl, -0-C=.,-alkylene, -CO-C~.,-alkyl, -C,~-alkyl-NHI, -C,~-alkyl-OH, -C,~-alkyl=NOH, -COOH, -C00-C,~-alkyl, -C00-phenyl, -C00-benzyl, -CONRaR', -C,O-C,.,-alkyl-NHz, -S(~OH, -SOZ-C,.,-alkyl or -SOrphenyl;
R° ..denotes phenyl-C,.,-alkyl, preferably benzyl, phenyl-Cz.°-alkenyl or phenyl-CZ$-alkynyl, wherein the phenyl ring may be optionally 3 0 . substituted by halogen, preferably chlorine or fluorine, hydroxy, C,~-alkyl, C,~-alkoxy, benzyloxy, phenylvxy, -NRaR9, -OCO-C,.,-alkyl, 25771-646 (S1 -0CO-phenyl, -OCO-benzyi, -OCO-pyridyl, -O-C2~-alkytene.
-CO-C,~-alkyl, -C,.,-alkyl-NReR9, -C,.~-alkyl-OH, -C,.~-alkyl=NOH, -COOH, -COO-C,~-alkyl, -COO-phenyl, -COO-benzyl. -CONR8R9, -CO-C,~-alkyl-NH2, -SOzOH, -SOZ-C,~-alkyl or -SOZ-phenyl;
Re denotes a 5- or 6-mernbered heterocydic group optionally C- or N-linked either directly or via a C,.~-alkyiene txidge, which contains one, two or three heteroatoms selected from nitrogen or oxygen and is optionally mono- or poiysubstituted by benzyl or C, ~-alkyl;
R° denotes a C~.e-cycioalkyl or C~-cydoalkyl-C,~-alkyl group which may optionally be substituted by =O, hydroxy, C,.,-alkyl or C,.,-alkyloxy;
R° denotes norbomyl, norbomenyl, adamantyl or noradamantyl optionally substituted by C,.~-alkyl, preferably methyl;
R° denotes -CHO, -COOH, -COO-C,.~-alkyl, -C00-phenyl, -COO-benzyl or .
-CONR8R9; or R° denotes an amine of general formula NR°R9;
R° denotes hydrogen, a branched or unbranched C,~-alkyl group; or Re denotes a C-linked 5- or 6-membered heterocydic group which contains one, two or three heteroatoms seleded from the group comprising nitrogen, oxygen and sulphur and is optionally substituted by benzyi, 2o C»-alkyl, C,~-alkyloxy, halogen, -CN, -NOz, -NHz, -OH or =O; and R9 denotes hydrogen, a txanched or unbranched C,.s-alkyl group; or R9 denotes a C-linked 5- or 6-membered heterocycfic group which contains ors, two or three heteroatoms selected from the group comprising nitrogen, oxygen or sulphur and is optionally substituted by benzyl, C~.i=alkyl, C,.s-alkyloxy, halogen, -CN, -NOZ, -NH2, -OH or =0;
or Ra and R9 together with the nitrogen atom forth a saturated or unsaturated 5- or fi-rnembered ring which may contain nitrogen or oxygen as additional heteroatoms, whilst the heterocyclic group may be 25771-646(S) substituted by a branched or unbranched C, ~-alkyl group, preferably methyl, or by a -(CH2),.,-phenyl group, preferably benzyl, optionally in the form of their racemates, snantiomers, diastereomers 5 and mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.
Also preferred are compounds of general formulae (la) and (Ib) 0 R, 0 Rv N N 2 Rv N N z ( i~'- R ~ I ~ R
N~ N N N~_ N
N R
RB~ Ib R (la) ( ) wherein R' or R3 denotes hydrogen, C,.~-alkyl, preferably C,.~-alkyl and benzyi;
~5 R2 denotes hydrogen, C,.s-alkyl, preferably C,~-alkyl;
RZ denotes cydopentyl, cydohexyl, cydopentanone, cyclohexanone, hydroxycyclopentane or hydrocydohexane;
2o R2 denotes a morpholine group optionally substituted by C,~-alkyl, preferably methyl, a piperidinyl group, a piperazinyi group optionally substituted by benzyl or C,.~-alkyl, preferably methyl, pyridyl, tetrahydrofuranyl, tetrahydropyranyl or furyl;
25 RZ denotes a phenyl group optionally substituted by C,.~-alkyl, halogen or hydroxy;
R2 denotes a phenyl-C,.~-alkyl, preferably benzyl, wherein the phenyl ring is optionally substituted by halogen, preferably fluorine or chlorine, C,.,-alkyl, C,~,-alkyloxy, hydroxy or NRBRg;
RZ denotes an amine of general formula NReR9; or 25771-646(S) R2 denotes a norbornenyl, norbornyl, adamantyl or noradamantyl optionally substituted by C,_4-alkyl, preferably methyl;
R4 denotes, C1_;-a:Lkyl, preferably C1_5-alkyl, phenyl -C1_;-alkyl, preferably benzyl, wherein the phenyl ring may be substituted by halogen, preferably chlorine or fluorine, hydroxy, C1_4-alkyl, C1_4-alkyloxy or NRaR9;
R6 denotes hydrogen, C»-alkyl, preferably C~.~-alkyl, wherein the alkyl chain may be substituted by halogen, hydroxy, =O, C»-alkyloxy, NR$R9, phenyloxy, -O-phenyl-0- C»-alkyloxy, benzyloxy, -O-benzyl-O-C»-aikyloxy, -OCO-C»-alkyl, -OCO-phenyl, -OCO-pyridyl, -OCO-benzyl, -O- C2.~-alkylene, -CO-C»-alkyl, -CHO, =NOH, -COOH, -C~00-C,~-alkyl; -COO-phenyl, =COO-benzyl, -CONR8R9, -NHGO~-C»-alkyl, -NHCO-phenyl, -CO-C»-alkyl-NR$R9, -S020H, -S02-C,~-alkyl or -S02-phenyl;
Rs denotes phenyl, wherein the phenyl ring may be substituted by halogen, preferably fluorine or- chlorine, hydroxy, C~.~-alkyl, C»-alkyloxy or NR8R9;
Rs denotes phenyl-C~_:3-alkyl, preferably benzyl, wherein the phenyl ring 2 ~ may be substituted by halogen, preferably fluorine or chlorine, hydroxy, Cm-alkyl, C~.~-alkyloxy, benzyloxy, phenyloxy, NR8R9, -OCO-Cm-alkyl, -OCO-phenyl, -OCO-benzyl, -OGO-pyridyl, -O-C2~,-alkylene, -CO-C»-alkyl, -C,~~-alkyl-NR8R9, -C»-alkyl-OH, -C»-alkyl=NOH, -COOH, -COO-Cap-alkyl, -COO-phenyl, -COO-benzyl, -CONR8R9, -CO-C~~,-alkyl-NR8f~9, -SO20H, -S02-C»-alkyl or -S02-phenyl;
R6 denotes a cyclopentyl, cyclohexyl, cyclohexyl- C, _3-alkyl, preferably cyclohexylmethyl, cyclopentanone, cyclohexanone, hydroxycyclopentane or hydroxycyclohexane linked via a single bond or via a Cm-alkylene chain;
3 o R6 denotes a furan, tetrahydrofuran, rx-pyran, y-pyran, dioxolane, tetrahydropyran, dioxane, thiophene, thiolane, dithiolane, pyrroie, pyrroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidir~e, triazolc~, pyridine, piperidine, pyridazine, pyrimidine, 25771-646(S) pyrazine, piperazine, triazine, morpholine, thiomorpholine, oxazole, isoxazole, oxazine, thiazoie, isothiazole, thiadiazole, oxadiazole or pyrazolidine linked via a single bond or via a C,~-aikylene chain;
Re denotes -CHO, -COOH, -C00-C,.~-alkyl; -C00-phenyl, -COO-benzyl, -CO-NH-C,.~-alkyl, -CO-N(C,.a alkyl)Z or -CO-NH-phenyl; or R° denotes an amine of genera! formula NR°R°;
R° denotes hydrogen, a brarxhed or unbranched C,.~-alkyl group; or R° dsnvtes a C-linked pyrrols, pyrroiine, pyrrvlidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, t5 pyridazine, pyrimidine, pyrazine, piperazine, morpholine, vxazole, isoxazole, thiazole, isothiazole or thiadiazole optionally substituted by chlorine, bromine, C,.~-alkyl, C,.a-alkyloxy, NOZ, NH2 or OH; and R9 denotes hydrogen, a t~anched or unbranched C~.,-alkyl group; or R° denotes a C-linked pyrrole, pyrroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoiine, imidazolidine, triazoie, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, morpholine, oxazole, isoxazole, thiazole, isothiazole or thiadiazoie optionally substituted by chlorine, bromine. C,.~-alkyl, C,.~-alkyloxy, NOz, NHZ, OH, or R° and R9 together with the nitrogen atom form a saturated or unsaturated 5- or 6-membered ring which may contain nitrogen or oxygen as additional heteroatoms, wherein the heterocyctic group may 3o be substituted by a branched or unbranched C~.,-alkyl group, preferably methyl, or by a -(CH=)~.s-phenyl group, preferably benzyl, optionally in the form of the racemates, the enantiomers and the diastereomers tti~reof and mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.

25771-646(S) 28, Other preferred compounds are those of general formula (Ib) O
RAN N
N~N N
R° (Ib) wherein R= denotes hydrogen, C,.,-alkyl, phenyl, benzyl, wherein the phenyl ring is bY ~b~~ed bY ~, PY~dI~. piP~dinyl, morpholinyl, g pipxatinyl, 4-benzy~peraZinyi, furyl, tetrahydrofuranyl, tetrahydropyranyl, NR°R°, cydopentyl, cydohexyl, adamantyl, noradamantyl, norbomyl a norbomenyl;
R' denotes hydrogen, C~a-alkyl or benzyl;
R4 denotes, Ct_s-alkyl yr benzyl;
1 o R° denotes hydrogen, C,.,-alkyl, prefera~iy methyl, which may optionally be s~stituted by OH, chlorine, bromine; C~.,-alkyloxy or NR°R9, -CHO, -COOH, -COO-C,~-alkyl, preferably -COOCH~, phenyl, phenyl-C,.ralkyi opfionaqy substituted by fluorine or benzylo~cy, preferably benzyl, Phenyloxy-C~.ralkyl optionally substituted by 15 xY. preferably phenyioxymethyl, benzytoxy-C~a-alkyl optionally . substkuted by methoxy, preferably benzytoxymethyl, benzyloxybenzyl, benzoyioxymethyl, pyridyhrba~ylo~rtrothyl, cyclopentyl, furyl, cyclohexylmsthyl, pyridylmsthyl, N-pyrrolylmethyl or N-nrorpholinomethyl;
2 o R° . denotes hydrogen, C,-ralkyl or pyridyl; and R° denotes hydrogen, C~.,-a~Cyl or pyridyl, optionally in the form of the racemates, the enantiomers and the diast~revmers thereof and mixtures thereof, and optionally the pharmacologically acceptable aad addition salts thereof.

25771-646(S) Other preferred compounds are those of genera! formula ( la) O R~

N
RwN I /~RZ
N~ N N
_~
N
Rs (la) wherein R' denotes hydrogen, C,_s-alkyl or benzyl;
R2 denotes hydrogen, C»-alkyl, phenyl, benzyl, wherein the phenyf ring is optionally fluorine-substituted, pyridyl, piperidinyl, morpholinyl, piperazinyl, 4-benzylpiperazinyl, furyf, tetrahydrofuranyl, tetrahydropyranyl, NR$R9, cyclopentyf, cycfohexyl, adamantyl, noradamantyl, norbornyl or norbornenyl;
R4 denotes, Cl_s-alkyl or benzyl;
to Rs denotes hydrogen, C,.a-alkyl, preferably methyl, which may optionally be substituted by OH, chlorine, bromine, C,.~-alkyloxy or NR8R9, -CHO, -COOH, -COO-C,.a-alkyl, preferably -COOCH3, phenyl, phenyl-C»-alkyl optionally substituted by fluorine or benzyloxy, preferably benzyl, phenyloxy-C,_3-alkyl optionally substituted by methoxy, preferably phenyloxymethyl, benzyloxy- C,_3-alkyl, optionally substituted by methoxy, preferably benzyloxymethyf, benzyloxybenzyl, benzoyloxymethyl, pyridylcarbonyloxymethyl, cyclopentyl, furyl, cyclohexytmethyf, pyridylmethyf, N-pyrrolylmethyl or N-morpholinomethyl;
2 o R$ denotes hydrogen, C»-alkyl or pyridyl; and R9 may denote hydrogen, C,.~-alkyl or pyridyl, optionally in the form of the racemates, the enantiomers, the diastereomers thereof and mixtures thereof and optionally the pharmacologically acceptable acid addition salts thereof.

25771-646(5) Also of interest are compounds of general formula (Ic) O R' .
N
I ~~-- RZ
R~N N N
N
Rs (Ic) 5 wherein R' denotes hydrogen or C,_3-alkyl;
Ra denotes hydrogen, C~~-alkyl, cyclopentyl, cyclopentanone, hydroxycyclopentane, furan or benzyl;
RS denotes C~.s-alkyl, preferably C~.a-alkyl, most preferably methyl, ethyl or tert.-butyl; and t5 R6 denotes hydrogen, benzyl or cyclopentyl, optionally in the form of the racemates, the enantiomers, the diastereomers and mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.
2o Also of interest are compounds of general formula (Id) O
N
y' R2 R,N N
Rs =-N
Rs (Id) wherein 25 R' denotes hydrogen or C~_3-alkyl;
RZ denotes hydrogen, C,~-alkyl, cyclopentyl, cyclopentanone, hydroxycyclopentane, furan or benzyl;

25771-646(S) R5 denotes C,.s-alkyl, preferably C,.~-alkyl, most preferably methyl, ethyl or tert.-butyl; and Rs denotes hydrogen, benzyl or cyciopentyl, optionally in the form of the racemates, the enantiomers, the diastereomers and mixtures thereof, and optionally the pharmacologically acceptable acid addition salts tfiereof.
Also preferred are compounds of general formula (Ib) N
RwN I \~RZ
N~ N N

Rs (Ib) wherein R2 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, 1 o phenyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 2-furyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMe2, cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yi, norboman-2-yl or 5-norbornen-2-yi;
R3 denotes hydrogen, methyl, ethyl, n-propyl or benzyl;
R4 denotes methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl,n-pentyl or benzyl; and Rs denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyi, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridyimethyl, cyclohexylmethyl, phenyiethyl, N-morpholinomethyl, 2o N-pyrrolylmethyl, (3-pyridyi)-NH-CHr, PhCO-O-CH2-, pyridyl-CO-O-CHr, Ph-0-CHr, (4-Me0-Ph)-0-CHr, (4-Me0-Ph)-CH2-0-CH2-, (4-Ph-CHz-0-Ph)-CH2-, 4-F-Ph-CHZ-, 3,4-F-Ph-CHI-, -COOH, -COOMe, -CHrOH, -CH2-OMe, -CH20Et or -CHrNMe2, 2577:.-646 (S7 optionally in the farm of the racemates, the enantiomers, the diastereomers and mixtures thereof and optionally the pharmacologically acceptable acid addition salts thereof.
Of particular interest are compounds of general formula (la) 0 R' N
RwN I /~RZ
N/\N N
~r ~~.-N
Rs (la) wherein R' denotes hydrogen, methyl, ethyl, n-propyl or benzyl;
R2 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyi, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 2-furyl, 3-tetrahydrofuranyl, 4-1 o tetrahydropyranyl, -NMe2, cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norboman-2-yl or 5-norbomen-2-yl;
R4 denotes methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, n-pentyl or benzyl; and Rs denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, I S phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyi, 3-pyridylmethyl, 4-pyridyimethyi, cyciohexyimethyl, phenylethyl, N-morpholinomethyl, N-pyrrolyimethyl, (3-pyridyi)-NH-CHr, PhCO-0-CHr, pyridyl-CO-0-CHr, Ph-0-CHr, (4-Me0-Ph)-0-CHz-, (4-Me0-Ph)-CHrO-CHI-, (4-Ph-CHrO-Ph)-CH2-, 4-F-Ph-CH2-, 20 3,4-F-Ph-CHI-, -COOH, -COOMe, -CHI-OH, -CH2-OMe, -CH20Et or -CHrNMe2, optionally in the form of the racemates, the enantiomers, the diastereomers and mixtures thereof and optionally the pharmacologically acceptable acid addition salts thereof.

25771-646(S) Also preferred are compounds of general formula (Ib) N
RwN I \~RZ
N/'N N
Ra N
RB , (Ib) wherein R= denotes hydrogen, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, 2-pyridyi, 3-pyridyl, 4-pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyi, 4-benzylpiperazinyl, 3-tetrahydrofuranyl, 4-tetrahydro-pyranyl, -NMe2, cyciopentyl, cydohexyl, adamantan-1-yi, noradamatan-3-yi, norboman-2-yl or 5-norbomen-2-yl;
R3 denotes hydrogen:
(~4 denotes methyl, sthyl, n-propyl, i-propyl, n-butyl, - 10 tert.-butyl, n-pentyl or benzyl; ar_d Re denotes hydrogen, methyl, ethyl, n-propyi, i-propyi, n-butyl, tert.-butyl, phenyl, benzyl, cydopentyl, 2-furyi, 2-pyridyimethyl, 3-pyridylmethyi, 4-pyridyimethyi, cydohexylmethyi, 2-phenylethyi, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl)-NH-CHZ-, Ph-C00-CHz-, 3-pyridyl-COO-CHr, Ph-0-CHr, (4-Me0-Ph)-0-CHZ-, (4-Me0-Ph)-CH2-0-CHr, 4-F-Ph-CHr-, 3,4F-Ph-CHz-, -CHZ-OH, -CHz-OMe, -CH2-OEt, -CH=-NMeZ, -COOMe or -COOH, optionally in the forth of the racemates, the enantiomers, the diastereomers and mixtures thereof, and optionally the pharmacologically acceptable acid addition salts thereof.

25771-646(S) Also of particular interest are compounds of general formula (la) O R' RAN N
i ~~ R2 N/'N N
=N
Rs (la) wherein R' denotes hydrogen;
R= denotes hydrogen, ethyl, n-propyi, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, 2-pyridyl, 3-pyridyi, 4-pyridyi, N-piperidinyi, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 3-tetrahydrofuranyi, 4-tetrahydro-pyranyl, -NMe2, cyclopentyi, cydohexyl, adamantan-1-yl, noradamatan-3-yl, norboman-2-yi or 5-norbomen-2-yi;
Rd dewte~ me=hv~, ethy'_, n-propyl, i-propyl, n-butyl, tert.-butyl, n-pentyl or benzyl; and Rg denotes hydrogen, methyl, ethyl, n-Ixopyl, i-propyi, n-butyl, tart.-butyl, phenyl, benzyl, cyclopentyl, 2-furyi, 2-pyridylmethyl, 3-pyridylmethyi, 4-pyridyimethyl, cydohexyimethyl, 2-phenylethyl, N-morphoiinomethyi, N-pyrrolylmethyl, (3-pyridyi)-NH-CHZ-, Ph-C00-CHZ-, 3-pyridyl-COO-CHz-, Ph-0-CH2-, (4-Me0-Ph)-O-CHr, (4-Me0-Ph)-CH2-0-CHr, 4-F-Ph-CHZ-, 3,4-F-Ph-CHr, -CH2-OH, -CH2-OMe, -CH2-OEt, -CHTNMe2, -COOMe or -COOH, optionally in the form of the racemates, the enantiomers, the diastereomers and mixtures thereof, and optionally the pharmacologically acceptable aad additi~ salts thereof.

In addition, the invention relates to a new category of compounds which contain basic structures of general formulae (la) to (Id).
O -~, 0 ~N N ~N N
N~ ~ I N~
N N N N ~ (Ib) -N (la) -N

Q ~ O
N N N N
~~ ~ I N~
~~N N N ~N N
(Ic) -.N . .~.r~ (Id) Preferred compounds are derivatives of general formula N
N ~ ,~
N/\N N
-'N
which have a substituent in positions 2, 4 and 7.
If required, the compounds of general formulae (la) to (Id) may be converted into the salts thereof, particularly, for pharmaceutical use, into the physiologically acceptable salts thereof with an inorganic or organic acid. Suitable acids for this purpose include hydrochloric acid, hydrobromic acid, sulphuric acid, phosphoric acid, methanesulphonic acid, acetic acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or malefic acid. Moreover, mixtures of these acids may be used.
The alkyl groups meant here (including those which are components of other groups) are branched and unbranched alkyl groups having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms, such as: methyl, ethyl, n-propyl, iso-propyl, butyl, iso-butyl, sec.-butyl, tert.-butyl, pentyl, iso-pentyl, hexyl, heptyl and octyl.

Unless otherwise specified, substituted alkyl groups (including those which are components of other groups) may, for example, carry one or more of the following substituents: halogen, hydroxy, mercapto, C~-s-alkyloxy, amino, alkylamino, dialkylamino, cyano, nitro, =O, -CHO, -COOH, -COO-C~_s-alkyl, -S-C~_s-alkyl.
Alkenyl groups (including those which are components of other groups) are the branched and unbranched alkenyl groups with 2 to 10 carbon atoms, preferably 2 to 3 carbon atoms, provided that they have at least one double bond, e.g. the alkyl o groups mentioned above provided that they have at least one double bond, such as for example vinyl (provided that no unstable enamines or enolethers are formed), propenyl, iso-propenyl, butenyl, pentenyl and hexenyl.
Unless otherwise specified, substituted alkenyl groups, (including those which are ~5 components of other groups), may for example carry one or more of the following substituents: halogen, hydroxy, mercapto, C~_s-alkyloxy, amino, alkylamino, dialkylamino, cyano, nitro, =O, -CHO, -COOH, -COO-C~_s-alkyl, -S-C~_s-alkyl.
The term alkynyl groups (including those which are components of other groups) 2o refers to alkynyl groups having 2 to 10 carbon atoms provided that they have at least one triple bond, e.g. ethynyl, propargyl, butynyl, pentynyl and hexynyl.
Unless otherwise specified, substituted alkynyl groups, (including those which are components of other groups), may for example carry one or more of the following 25 substituents: halogen, hydroxy, mercapto, C~_s-alkyloxy, amino, alkylamino, dialkylamino, cyano, nitro, =O, -CHO, -COOH, -COO-C~_s-alkyl, -S-C~_s-alkyl.
Examples of cycloalkyl groups having 3 to 6 carbon atoms include cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, which may also be substituted by branched or so unbranched C,_4-alkyl, hydroxy andlor halogen or as hereinbefore defined.
The term halogen generally refers to fluorine, chlorine, bromine or iodine.
The word aryl denotes an aromatic ring system having 6 to 10 carbon atoms which, unless otherwise specified, may carry one or more of the following substituents, for 35 example: C~_s-alkyl, C,_s-alkyloxy, halogen, hydroxy, mercapto, amino, alkylamino, dialkylamino, CF3, cyano, nitro, -CHO, -COOH, -COO-C~_s-alkyl, -S-C~_s-alkyl.
The preferred aryl group is phenyl.

Examples. of N-linked cyclic groups of general formula NR$R9 are as follows:
pyrrole, pyrroline, pyrrolidine, 2-methylpyrrolidine, 3-methylpyrrolidine, piperidine, piperazine, N-methylpiperazine, N-ethylpiperazine, N-(n-propyl)-piperazine, N-benzylpiperazine, morpholine, thiomorpholine, imidazole, imidazoline, imidazolidine, pyrazole, pyrazoline, pyrazolidine, preferably morpholine, N-benzylpiperazine, piperazine and piperidine, wherein the above-mentioned heterocycles may also be substituted by C~~-alkyl, preferably methyl, or may be substituted as in the definitions.
o Examples of C-linked 5- or 6-membered heterocyclic rings which may contain nitrogen, oxygen or sulphur as heteroatoms include, for example, furan, tetrahydrofuran, 2-methyltetrahydrofuran, 2-hydroxymethylfuran, tetrahydrofuranone, y-butyrolactone, a-pyran, y-pyran, dioxolane, tetrahydropyran, dioxane, thiophene, dihydrothiophene, thiolane, dithiolane, pyrrole, pyrroline, s pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, tetrazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, tetrazine, morpholine, thiomorpholine, oxazole, isoxazole, oxazine, thiazole, isothiazole, thiadiazole, oxadiazole and pyrazolidine, whilst the heterocycle may be substituted as in the definitions.
"=O" means an oxygen atom linked by a double bond.
The compounds according to the invention have an affinity for adenosine receptors 2s and thus constitute a new category of adenosine antagonists. In general, adenosine antagonists may exhibit a therapeutically useful activity in cases where diseases or pathological situations are connected with the activation of adenosine receptors.
Adenosine is an endogenous neuromodulator with predominantly inhibitory effects on 3o the CNS, heart, kidneys and other organs. The effects of adenosine are mediated through at least three receptor subtypes: adenosine A~, A2 and A3 receptors.
In the CNS, adenosine develops inhibitory effects predominantly by activating A~
receptors: presynaptically by inhibiting synaptic transmission (inhibiting the release of 35 neurotransmitters such as acetylcholine, dopamine, noradrenalin, serotonin, glutamate, etc.), and postsynaptically by inhibiting neuronal activity.
A~ antagonists cancel out the inhibitory effects of adenosine and promote neuronal transmission and neuronal activity.

A~ antagonists are therefore of great interest in the treatment of degenerative diseases of the central nervous system such as senile dementia of the Alzheimer's type and age-associated disorders of memory and learning performance.
The disease includes, in addition to forgetfulness in its mild form and total helplessness and absolute dependence on care in the most severe form, a range of other accompanying systems such as sleep disorders, motor-coordination disorders up to the clinical picture of Parkinson's disease as well as increased lability affect and 1o depressive symptoms. The disease is progressive and can result in death.
Therapy up till now has been unsatisfactory. Hitherto, there has been a complete absence of specific therapeutic agents. Attempts at therapy with acetylcholinesterase inhibitors exhibit some effect in a small proportion of patients but are connected with a high level of side effects.
The pathophysiology of Alzheimer's disease and SDAT is characterised by a severe impairment of the cholinergic system, but other transmitter systems are also affected.
As a result of the loss of presynaptic cholinergic and other neurons and the resulting lack of provision of neurotransmitters, neuronal transmission and neuronal activity is 2o significantly reduced in the areas of the brain essential for learning and memory.

Selective adenosine A~ receptor antagonists promote neuronal transmission by increased provision of neurotransmitters, they increase the excitability of postsynaptic neurons and can thus counteract the symptoms of the disease.
The high receptor affinity and selectivity of some of the compounds claimed should make it possible to treat Alzheimer's disease and SDAT with low doses, so that hardly any side effects can be expected which cannot be attributed to the blockade of A~ receptors.
Another indication for centrally acting adenosine A~ antagonists is depression. The therapeutic success of antidepressant substances appears to be connected to the regulation of A~ receptors. A~ antagonists may lead to the regulation of adenosine A~
receptors and thus present a new therapeutic approach to the treatment of depressive patients.
Other fields of use particularly for A2-selective adenosine antagonists are neurodegenerative diseases such as Parkinson's disease and also migraine.
Adenosine inhibits the release of dopamine from central synaptic nerve endings by interaction with dopamine-D2 receptors. A2 antagonists increase the release and availability of dopamine and thus offer a new therapeutic principle for treating Parkinson's disease.
In migraine, vasodilation of cerebral blood vessels mediated by A2 receptors appears to be involved. Selective A2 antagonists inhibit vasodilation and may thus be useful in treating migraine.
1o Adenosine antagonists may also be used in the treatment of peripheral indications.
For example, the activation of A~ receptors in the lungs may lead to bronchoconstriction. Selective adenosine A~ antagonists relax the smooth muscle of the trachea, cause bronchodilation and may thus be useful as antiasthmatic agents.
By activating A2 receptors, adenosine may also lead, under certain circumstances, to respiratory depression and stoppage of breathing. A2 antagonists cause respiratory stimulation. For example, adenosine antagonists (theophyllin) are used for treating respiratory distress and for preventing "sudden infant death" in premature babies.
Important fields of therapy for adenosine antagonists are also cardiovascular diseases and kidney diseases.
In the heart, adenosine causes inhibition of electrical and contractile activity by activating A~ receptors. In conjunction with coronary vasodilation mediated by receptors, adenosine has a negative chronotropic, ionotropic, dromotropic, bathmotropic and bradycardiac effect and lowers the minute output.
Adenosine A~ receptor antagonists are able to prevent damage to the heart and lungs caused by ischaemia and subsequent reperfusion. Consequently, adenosine antagonists may be used for the prevention and early treatment of damage to the heart caused by ischaemic reperfusion, e.g. after coronary bypass surgery, heart transplants, angioplasty or thrombolytic treatment of the heart and similar interventions. The same is true of the lungs.
In the kidneys, the activation of A~ receptors causes vasoconstriction of afferent arterioles and, consequently, a fall in renal blood flow and glomerular filtration. A~
antagonists act as powerful potassium-saving diuretics on the kidneys and can thus be used for kidney protection and for the treatment of oedema, renal insufficiency and acute renal failure.
5 Because of the adenosine antagonism on the heart and the diuretic activity, A~
antagonists may be used to therapeutic effect for various cardiovascular diseases, such as cardiac insufficiency, arrhythmias (bradyarrhythmias) associated with hypoxia or ischaemia, conduction disorders, hypertension, ascites in liver failure (hepato-renal syndrome) and as an analgesic in circulatory disorders.
~o Surprisingly, some of the compounds according to the invention display an affinity for the A3-adenosine receptor. A3 antagonists inhibit the degranulation of mast cells caused by activation of the A3 receptor and are therefore therapeutically useful in all diseases and pathological situations connected with mast cell degranulation;
e.g. as ~5 anti-inflammatory substances in hypersensitivity reactions such as asthma, allergic rhinitis, urticaria, in myocardial reperfusion injury, scleroderma, arthritis, autoimmune diseases, inflammatory bowel diseases, and the like. Cystic fibrosis - also known as mucoviscidosis - is a congenital metabolic disorder caused by a genetic defect on a certain chromosome. As a result of increased production and increased viscosity of 2o the secretions of the mucous glands in the bronchi, there may be severe complications in the airways. Early investigations have shown that A~
antagonists increase the efflux of chloride ions, e.g. in CF PAC cells. On the basis of these findings it is to be expected that the compounds according to the invention will regulate the disrupted electrolyte bands of the cells and alleviate the symptoms of the 25 disease in patients suffering from cystic fibrosis (mucovicidosis).
The A~ receptor binding values obtained have been determined analogously with Ensinger et al. in "Cloning and functional characterisation of human A~
adenosine receptor - Biochemical and Biophysical Communications, Vo.187, No. 2, 919-926, 30 1992" and are assembled in Table 20.
The As receptor binding values assembled in Table 21 were determined analogously to Salvatore et al. "Molecular cloning and characterization of the human A3-adenosine receptor" (Proc. Natl. Acad. Sci. USA 90, 10365-10369, 1993).
The new compounds of general formula (la) to (Id) may be administered orally, transdermally, by inhalation or parenterally. The compounds according to the invention are present as active ingredients in conventional preparations, e.g.
in compositions consisting essentially of an inert pharmaceutical carrier and an effective dose of the active substance, such as for example plain or coated tablets, capsules, lozenges, powders, solutions, suspensions, emulsions, syrups, suppositories, transdermal systems, etc. An effective dose of the compounds according to the invention is between 1 and 100, preferably between 1 and 50, most preferably between 5 and 30 mg/dose for oral use, between 0.001 and 50, preferably between 0.1 and 10 mg/dose for intravenous or intramuscular use. According to the invention, solutions containing 0.01 to 1.0, preferably 0.1 to 0.5% active substance are suitable for inhalation. It is preferable to use powders for administration by inhalation. It is also possible to use the compounds according to the invention as a solution for infusion, preferably in physiological saline or nutrient saline solution.

The compounds according to the invention may be prepared by the following methods. In order to synthesise the two isomers O R' O
RvN N R~ N
i~R2 ~ ~ yR2 Ni N N Ni N N
s~N s~N Rs R (la) R (Ib) of general formula (la) and (Ib), wherein the substituents are as hereinbefore defined, the following procedure is used.
In a first step, aminoguanidine (1 ) is reacted with a carboxylic acid derivative of general formula (2) to obtain a triazole of general formula (3) (diagram 1 ).
This reaction may be carried out in accordance with the procedures published in J.
Chem.
Soc. 1929, 816; J. Org. Chem 1926, 1729 or Org. Synthesis 26, 11.
N R6-COOH N ~ NH
N + oder Step 1 Rs -.<~
~N~N

(1) (2) (3) Diagram 1:

Then, in a second step, the triazole of general formula (3) is reacted with alkylcyanoacetate in a cyclising reaction under alkaline conditions to obtain a triazolopyrimidine of general formula (4) (Diagram 2).
O
H~ N
Rs N , NH Step 2 >=N
(3) Rs (4) Diagram 2:
The base may be an alkali or alkaline earth metal alkoxide, e.g. of methanol, ethanol, 1o isopropanol, n-, sec- or tert.-butyl alcohol. Suitable alkali ands alkaline earth metals include for example lithium, sodium, potassium, magnesium and calcium. Sodium methoxide, sodium ethoxide, sodium isopropoxide and potassium tert.-butoxide are particularly preferred as the base. Furthermore, alkali or alkaline earth metal hydroxides may be used as bases. The hydrides of sodium, lithium, potassium, ~5 magnesium and calcium are preferred. Suitable inert solvents are dimethylformamide, dimethylacetamide, methylene chloride and tetrahydrofuran.
Additionally, alkali or alkaline earth metal hydroxides of lithium, sodium, potassium, magnesium and calcium may also be used, but preferably sodium hydroxide, potassium hydroxide, lithium hydroxide and calcium hydroxide in alcoholic or 20 aqueous solution.
In addition to the alkylcyanoacetates, cyanoacetic acid may also be used. The mixture thus obtained is stirred at ambient temperature for 0.5 to 4 hours, preferably 1 to 2 hours and then mixed with a compound of general formula (3) and stirred for 2 25 to 12, preferably 4 to 6 hours, preferably at reflux temperature. The reaction mixture is then mixed with water at ambient temperature and acidified, after which the solid is filtered off, washed and dried. Examples of suitable acids are formic acid, acetic acid or inorganic acids such as hydrochloric or sulphuric acid.

In a third step, the groups R4 and R5 are introduced into the triazolopyrimidine of general formula (4) and the compounds of general formulae (5) and (12) are obtained (Diagram 3).
p 0 O

H N Step 3 R \ N N
-. ~ I + 5 N ~ N NH2 N ~ N NHZ RAN N NH2 6>=N ~N
R6 (4) R (5) R6 (12) Diagram 3:
For this, a compound of general formula (4) is dissolved in 5 to 40 times, preferably ~0 10 to 20 times the amount of a polar solvent, such as dimethylformamide, dimethylacetamide, methylene chloride or tetrahydrofuran, preferably dimethylformamide, and most preferably anhydrous, possibly absolute dimethylformamide. The resulting solution is combined with a base and a corresponding alkylating agent. Suitable bases include the alkali or alkaline earth metal carbonates of lithium, sodium, potassium and calcium such as sodium carbonate, lithium carbonate, potassium carbonate, calcium carbonate and preferably potassium carbonate. Moreover, the hydrogen carbonates of lithium, sodium and potassium may be used. It is also possible to use the alkali or alkaline earth metal hydroxides of lithium, sodium, potassium, magnesium or calcium, preferably sodium 2o hydroxide, potassium hydroxide, lithium hydroxide and calcium hydroxide in alcohols or water. Other bases which may be considered are the alkoxides of the alkali and alkaline earth metals already mentioned in step (2). Furthermore, the above-mentioned alkali and alkaline earth metal hydrides may be used, preferably in inert solvents such as dimethylformamide, dimethylacetamide, methylene chloride, ethers, 25 tetrahydrofuran and toluene. Suitable alkylating agents include alkyl halides, such as alkyl chloride, alkyl bromide, especially alkyl iodide and alkyl tosylates, mesylates, triflates and dialkylsulphates. The alkyl groups of the alkylating agents correspond to the definitions for R4 and RS given hereinbefore. The reaction mixture is stirred at ambient temperature for 0.5 to 4 days, preferably 1 to 2 days and evaporated to so dryness. The product can be worked up, on the one hand, by stirring the residue with water and a solvent, e.g. a halogenated solvent such as carbon tetrachloride, methylene chloride, preferably methylene chloride, whereupon the compound of general formula (5) can be isolated as a solid by filtering. The compound of general formula (12) can be obtained from the filtrate by removing the solvent.
Moreover, in the event that no solid is obtained, in order to isolate the compound of general formula (12) from the filtrate, the phases of the filtrate may be separated, the aqueous solution may be extracted with an halogenated solvent, preferably methylene chloride, and the combined organic phases may be dried and worked up.
The compounds of general formulae (5) and (12) are obtained by chromatographic purification of the residue (Diagram 3).
o By nitrosing a compound of general formula (5), a compound of general formula (6) is obtained in the fourth step (Diagram 4).
O O
R~ R~ NO
N Step 4 N I .
N NH ~ N NH
N _ I 2 N _ I z s~N s~N
R (5) R (6) Diagram 4:
According to the invention, there are two alternative processes which may be used.
Step 4, alternative A:
A compound of general formula (5) is dissolved or suspended in a polar solvent, the 2o polar solvent possibly consisting of any of the above-mentioned solvents and dimethylacetamide or an alcohol, e.g. methanol, ethanol, propanol, isopropanol and butanol. Dimethylformamide is particularly preferred. It is advisable to use the chosen solvent as an anhydrous, optionally absolute solvent. The mixture thus obtained is cooled to below 0°C, preferably -5°C. A nitrosing agent, e.g. an alkyl nitrite such as methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, tert.-butyl and pentyl nitrite, but preferably isoamyl nitrite, is added to this mixture, whilst the temperature should not rise above 0°C. The mixture is stirred at this temperature for 2 to 48, preferably 4 to 24, most preferably 8 to 12 hours. Then stirring is continued at ambient temperature if required to finish off the reaction. The solvent is eliminated 3o in vacuo, the residue is filtered with a solvent, e.g. diethylether, washed with water and the residue thus obtained is dried (in vacuo).

Step 4, alternative B:
A compound of general formula (5) is mixed with an aqueous acid, the acid being an organic acid, formic acid, acetic acid, propionic acid, preferably acetic acid or an inorganic acid, e.g. hydrochloric acid or dilute sulphuric acid, preferably hydrochloric 5 acid and mixtures thereof. The mixture is heated to 30 to 100, preferably 50 to 80, most preferably 70°C and mixed with a nitrosing agent, preferably sodium nitrite, most preferably sodium nitrite in water and kept at the above temperature for 0.5 to 2 hours, preferably 1 hour, and then kept for 0.5 to 2 hours, preferably 1 hour, at 0 to 20, preferably 5 to 15, most preferably 10°C. The product is filtered, the residue is o washed and dried in vacuo.
In the fifth step the nitroso compound (6) is reduced to form a diamine derivative of general formula (7) (Diagram 5) O O

Step ;
N N NH2 N ~ N NH2 s~N s~N
~5 R (6) R
Diagiram 5:
The following alternative methods may be used for this purpose.
Step 5, alternative A:
The nitroso compound (6) is suspended in water with stirring and combined with a suitable reducing agent. Suitable reducing agents are dithionite in acid or alkaline solution. Also ammonium sulphite, lithium, sodium or potassium hydrogen sulphite, triethylphosphite, triphenylphosphine or lithium aluminium hydride can be used.
Moreover, the nitroso group may be catalytically hydrogenated using transition metal catalysts based on palladium, platinum, nickel or rhodium or by transfer hydrogenation, e.g. with cyclohexane or ammonium formate as the hydrogen source.
However, it is preferable to use sodium dithionite. Apart from the aqueous ammonia 3o solution which is preferably used, alkali or alkaline earth metal hydroxide solutions, e.g. lithium, sodium, potassium hydroxide or magnesium, calcium and barium hydroxide solutions, but preferably the dilute solutions, may be used as bases.
Furthermore, the methyl, ethyl, isopropyl, n-propyl, isobutyl, tert.-butyl and n-butyl alkoxides of the above-mentioned alkali and alkaline earth metals may be used.
This suspension is heated to 20 to 100°C, preferably 50 to 90°C, most preferably 60 to 80°C and mixed with an acid, preferably at the beginning, but most preferably within the first 30 minutes. Possible acids are inorganic acids, hydrochloric and sulphuric acid and organic acids such as formic acid and acetic acid and mixtures thereof, sulphuric acid being preferred whilst 50% sulphuric acid is particularly preferred. The resulting mixture is refluxed until the reaction is complete. On cooling, the product is precipitated as a hemisulphate. Moreover, the product can be precipitated by o neutralising with an aqueous base, e.g. lithium hydroxide, sodium hydroxide, potassium hydroxide, preferably sodium hydroxide solution, most preferably 30%
by weight sodium hydroxide solution by neutralising and then filtered off as a free base.
Step 5, alternative B:
95 The nitroso compound (6) is added to a mixture of aqueous base and an alcohol, with stirring. Then, after the nitroso compound has been dissolved or suspended, the reducing agent is added, preferably in solution. Possible reducing agents are those mentioned in Method A, an aqueous solution of sodium dithionite being particularly preferred. Then the mixture is stirred at ambient temperature for 0.5 to 6, preferably 20 1 to 4, most preferably 1.5 to 3 hours. The product precipitated is isolated by filtering.
In the sixth step, the isomeric compounds (8) are prepared from the diamines of general formula (7) (Diagram 6).
O O O
R~ N NH2 R~ NHCOR2 Rv N NH2 Step 6 N
N NH ~ ~ ~ N NHCOR2 N-N 2 N-N NH N~--.N
s~ s' 25 R (7) Rs (8) R
Diagram 6:
For this, the amino compound of general formula (7) is suspended in an organic solvent and mixed with an organic base. After the mixture has been kept at ambient temperature for 40 to 60 minutes, preferably 20 to 50 minutes, most preferably 25 to 30 45 minutes, the mixture is cooled to 0 to 15°C, preferably 5 to 10°C and combined with a carboxylic acid derivative wherein the group R2 is as hereinbefore defined.
Suitable organic solvents are dimethylformamide, dimethylacetamide, methylene chloride, toluene and tetrahydrofuran, of which dimethylformamide is preferred and anhydrous, optionally absolute dimethylformamide is particularly preferred.
Suitable organic bases are dimethylaminopyridine, pyridine, tert.-amines, such as trimethylamine, triethylamine, diisopropylethylamine, DBU
(diazabicycloundecene) or one of the inorganic bases mentioned earlier, particularly alkali or alkaline earth metal carbonates or hydrogen carbonates. However, dimethylaminopyridine is particularly suitable as the base. Carboxylic acid derivatives which may be used according to the invention are the carboxylic acid halides, preferably carboxylic acid chlorides or carboxylic acids if they are suitably activated. This may be done, for example, by o reacting with chloroformic acid esters, carbonyldiimidazole, carbodiimides, such as dicyclohexylcarbodiimide, EDAC, or benzotriazoles, such as HOBt (1-hydroxy-1-H-benzotriazole) and TBTU. Similarly, the corresponding aldehyde may also be used instead of the carboxylic acid derivative and the intermediate product may be oxidised with iron(II)chloride, azodicarboxylic acid esters and other oxidising agents.
~5 The mixture is then stirred at ambient temperature for 0.5 to 4 hours, preferably 1 to 3 hours, most preferably 2 hours, at 5 to 20°C, preferably 7 to 15°C, most preferably 10°C and overnight at ambient temperature and the solvent is then eliminated in vacuo. The residue is taken up in water, the solid is filtered off, washed and optionally purified by recrystallisation or chromatography, preferably column 2o chromatography.

In the seventh step, a compound of general formula (6), (7) or (8) is cyclised to form the compound of general formula (9) in accordance with methods A to C (Diagram 7) O
R~ N NHCOR2 ~.
I
N ~ N NH2 _ l s~N (8) R
O
O
RAN NH2 R~ N
I N I /~R2 N ~ N NH2 ~ N N
N_~
s (7) s~N (9) R R
O
RAN NO
I
N ~ N NH2 Method C
N
Rs (6) Diagram 7:
Step 7, Method A:
A compound of general formula (8) is suspended in an alcohol and refluxed with a base for 24 hours. After cooling, the mixture is made alkaline, the solid is filtered off o and dried. If desired, the product is purified by recrystallisation or chromatography, preferably column chromatography. Bases which may be used here include the alkali metal and alkaline earth metal hydroxides, e.g. the hydroxides of lithium, sodium, potassium, calcium and barium and mixtures thereof in the form of aqueous solutions or optionally in admixture with an alcohol and/or with a water-miscible ether.
Suitable alcohols are methanol, ethanol, n-propanol, isopropanol, n-butanol and tert.-butanol. Suitable ethers include, in particular, cyclic ethers, e.g.
tetrahydrofuran and dioxane. By analogous methods, cyclisation may also be carried out with inorganic acid chlorides such as thionyl chloride, phosphorusoxychloride or phosphorus pentachloride and with polyphosphoric acid.

Another analogous method consists of reacting the carboxylic acid amide under acid conditions with inorganic acid/methanol, preferably hydrochloric acid/methanol or under basic conditions with alkali metal/methanol, preferably sodium/methanol and then carrying out thermal cyclisation.
Step 7. Method B:
In another process it is possible to prepare the compound (9) wherein R2 is hydrogen starting from the diamine (7). To do this, (7) is stirred with an equimolar amount, o preferably with an excess of formamide for 0.5 to 3 hours, preferably 1 to 2 hours, most preferably 1.5 hours at 50 to 250°C, preferably 100 to 225°C, most preferably 180 - 200°C. The formamide remaining is distilled off in vacuo and the residue is taken up in water. The solid thus obtained is filtered off, washed with water and the resulting product is purified optionally by recrystallisation or chromatography, ~s preferably column chromatography. -Step 7, Method C:
Moreover, the compound of general formula (9) may be obtained directly from the nitroso compound of general formula (6) if RZ denotes a group NR$R9, wherein R$
2o and R9 are as hereinbefore defined. To a solution of the desired N-formylamine in diglyme, phosphorusoxychloride is added at -10 to +20°C, preferably -5 to +5°C, most preferably 0°C. Then the mixture is stirred in an ice bath and the nitroso compound (6) is added. The mixture is stirred for 15 to 120 minutes, preferably 30 to 80 minutes, most preferably 40 to 60 minutes, at 30 to 120°C, preferably 50 to 25 100°C, most preferably 70 to 80°C and then added to ice water. The solid product is filtered off, washed and dried and optionally purified by recrystallisation or purified by chromatography, preferably column chromatography.

The compounds of general formula (la) and (Ib) may be obtained in an eighth step from the compound of general formula (9) (Diagram 8).
O R~
R~ N

~ i />-R
~N N
R4 O H N_~
N
\ N N to 8 /~R2 ~ R + (la) N N O
N N
N l R\N
(9) ~ R2 R ~
~N N
N_~
~-' N R
s' Ib R ( ) Diagram 8:
For this, the starting compound is taken up in an organic solvent and reacted with a base and a suitable alkylating agent. The reaction mixture is stirred overnight at ambient temperature. If required, the reaction may also be carried out at elevated o temperature. The duration of the reaction may be up to one week under certain circumstances. When the reaction has ended the mixture is evaporated to dryness.
The residue is taken up in an aqueous alkaline solution, whilst the base may be lithium hydroxide, sodium hydroxide, potassium hydroxide, preferably sodium hydroxide and most preferably 2N sodium hydroxide solution. The solution is then 15 washed with a non-polar organic solvent such as benzene, toluene or xylene, preferably toluene and adjusted to a pH of 6. The solid precipitated is filtered off and optionally purified by chromatography, preferably column chromatography. In this way, both the dialkylation products and the monoalkylation products of the compounds of general formula (la) and (Ib) may be prepared and isolated.
Suitable organic solvents for the alkylation include inert solvents such as dimethylformamide, dimethylacetamide, methylene chloride, alkylether, preferably diethylether, tetrahydrofuran, benzene, toluene, xylene and particularly dimethylformamide. Suitable bases include carbonates such as lithium carbonate, 2s sodium carbonate, potassium carbonate, calcium carbonate and hydrogen carbonates of the above-mentioned alkali metals and alkaline earth metals as well as the hydroxides and alkoxides thereof. The alkoxides of the above-mentioned alkali and alkaline earth metals with methanol, isopropanol and tert.-butanol are preferred, sodium ethoxide being particularly preferred. In the case of the carbonates, hydrogen carbonates, alkoxides and hydroxides, it may be advantageous to use alcohol or water as solvent. Other bases which may be used for alkylation are sodium hydride, potassium hydride, lithium hydride and calcium hydride in the above-mentioned inert solvents. Moreover, suitable alkylating agents are hydrocarbon halides such as alkyl chlorides, alkyl bromides and alkyl iodides as well as hydrocarbon or alkyl tosylates, -mesylates and -triflates and the alkyl sulphates, alkyl iodides being preferred.
The invention further relates to a process for preparing compounds of general formula (Id) and (Ic) O R~ O
N ~ N~ R2 N ~ N~ RZ
R~N~N N RS~N~N N
~. Rs s/ N s~N
'S R (Ic) R (Id) Starting from a compound of general formula (12) a compound of general formula (13) may be obtained (Diagram 9) in accordance with the reaction of (5) to obtain (6) described hereinbefore (cf. Diagram 4, Step 4).

NO
~Ni I St~ ~Ni R~ ' _N NH R5~ ' _N NH
N ~ z N ~ z s~N (12) s~N (13) R R
Diagram 9:

This may be converted in accordance with the method of Step 5 (cf. Diagram 5) into a compound of general formula (14) (Diagram 10).
O O

Step 5 ~ I
R~N N NH2 ~ R~N N NH2 _ J _ I
s~N (13) s~N (14) R R
Diagram 10:
In accordance with the alternative methods described hereinbefore for reacting compound (7) to obtain compound (8) (cf. Diagram 6, Step 6) the compounds of general formula (14) may be converted into the compounds of general formula (15) (Diagram 11 ).
O O O

NI I Sty NI I + N
R~ ~ N NH R5 - ~ R~ ~ N NHCOR2 N -N 2 N -IV NH f V -N
s~ s~ s~
R (14) R (15) R
Diagram 11:

From this, the compounds of general formula (16) may be obtained (Diagram 12) in Step 7 in accordance with the alternative reactions of cyclisation described above (cf.
Diagram 7).
O

N
R~ ' _N NH
N
N
s~ (15) R
O O H

I Ni _ I / R
R~N N NH2 R~ ~N N
~N N_I
Rs (14) s~N (16) R
O
NO
Ni R5~ ~ N NH Method C
N ~ z ~.N
s/ (13) R
Diagram 12:

From these, the compounds of general formulae (Ic) and (Id) may be obtained by the alkylation reactions described in Steps 3 and 8 and may then be isolated if required by suitable methods of purification or separation, e.g. crystallisation or column chromatography (Diagram 13).
O R' N N
~~R2 O H R~N N N
I _ I
~- N
N N Ste 8 ~~R2 ~ R + (Ic) R~N N N O
_ I
s~N (16) N
R I I ~R
~N N

Id R ( ) Diagram 13:
By introducing suitably substituted groups R', R2, R3, R4, R5 or R6, the imidazotriazolopyrimidines (la), (Ib), (Ic) and (Id) which may be prepared by the methods described above can be further functionalised using generally known methods. If desired, suitable protecting groups may be used. Diagram 14 which follows illustrates, by way of example, possible modifications to the group R6 of the compounds (Ib) which may arise according to the invention.

The reactions outlined by way of example in Diagram 14 lead to reactive imidazotriazolopyrimidines which may be used as starting compounds for further structural variations (esterifications, alkylations, substitutions etc.).
According to the 5 invention, all the groups R', R2, R3, R4, RS or Rs may be functionalised.
These modifications are not restricted to compounds of general formula (Ib) but may also be transferred to the imidazotriazolopyrimidines of general formulae (la), (Ic) and (Id).
Diagram 14 serves as an explanation by way of example of possible structural variations of the imidazotriazolopyrimidines (la), (Ib), (Ic) and (Id), without restricting 9o the invention to the reaction sequences shown.
O
4 _ R ~ N Rs:
N R2 Me0 ~ ~ HZ O - CHzAIkyF-N / N N (Ib) ~ I Rs }=N
Rs Oxidation O O
R~ N Halogenation R~ N
N I ~~ RZ ---~ N ~ ~ R2 N // \ N N
N -N Rs N -N Rs R': -CH Ik I-, HO-R' ~ y X-R R . -CH2AIkyl-, X: Halogen, Oxidation Oxidation R~ N N R~ N
RZ N ~ ~~ R2 ~N N N
N I Ft3 N N
H N HO ~N R
R" R./.
R": -Alkyl-, R": -Alkyl-, Diagram 14:
The present invention is explained more fully by means of descriptions of synthesis of imidazotriazolopyrimidines given by way of example. These Examples serve as an ~5 illustration without restricting the invention to their scope.

Step 1: Synthesis of 5-substituted 3-amino-1,2,4-triazoles (31:
R6 N,N,H
~N

(3) The unsubstituted 3-amino-1,2,4-triazole is commercially obtainable, the 5-substituted 3-amino-1,2,4-triazoles required may be prepared in accordance with methods known from the literature as published, for example, in J. Chem. Soc.
1929, 816, J. Org. Chem. 1926, 1729 or Org. Synthesis 26, 11. The carboxylic acids R6-COOH and nitrites R6-CN are commercially obtainable or may be prepared by methods known from the literature.
Table 1:
No. R6 Yield M (C) (%) 1.1. -H commercially -obtainable 1.2. -Meth I 76 145-148 1.3. -Eth I 75 152 1.4. -n-Pro I 62 140-143 1.5. -i-Pro I 67 103-104 1.6. -n-But I 62 118 1.7. -t-Butyl 39 130-131 1.8. Benz I- 70 167-169 1.9. C clo ent I- 64 168-172 1.10. 2-Fu I- Hemisulfate 76 207-208 1.11. Phen I- 68 185-186 1.12. C clohex (meth I- 51 186-188 1.13. 2-Phen leth I- 53 139-140 1.14. (4-MeO-Ph)-O-CH2- 41 -1.15. (4-Me0-Ph)-CH2-O-CH2- 54 153 1.16. (4-Ph-CH20-Ph)-CH2- 57 196-200 1.17. 4-Fluorobenz I- 100 163-164 1.18. 3,4-Difluorobenz I- 81 135-137 1.19. 3-P rid Imeth I- 58 192-196 Step 2: Synthesis of 2-substituted 4H-7-amino-1,2.4-triazolof1,5-alpyrimidin-5-one derivatives (41 H. N
N i N NH2 s N
R (4) General method:
2.3g (0.1 mol) of sodium are dissolved in 10 ml of abs. ethanol, then 14.7 g (0.13 mol) of ethyl cyanoacetate are added. The mixture is stirred for 1 - 2 hours at ambient temperature, then mixed with 0.1 mol of the desired 5-substituted 3-o aminotriazole and refluxed for 4 - 6 hours. The cooled reaction mixture is mixed with water and made.acidic with stirring, then the solid is filtered off, washed and dried.
Using this process the following compounds were prepared:
Table 2:
No R6 Yield Mp (C) 2.1. -H 73 >370 2.2. -Meth I 76 >300 2.3. -Eth I 81 >300 2.4. -n-Pro I 80 290 Decom .

2.5. -i-Propyl 81 294 (Decomp.) 2.6. -n-But I 77 256 2.7. -t-But I 78 >300 2.8. Benz I- 82 300 Decom .

2.9. C clo ent I- 83 310 Decom .

2.10. 2-Fu I- 61 -2.11. Phen I- 75 -2.12. C clohex Imeth I- 81 > 300 2.13. 2-Phenylethyl- 83 295-296 2.14. (4-Me0-Ph)-O-CH2- 68 302 2.15. (4-Me0-Ph)-CH2-0-CH2-gg 245 2.16. (4-PhCH20-Ph)-CH2- 96 296-298 No R6 Yield Mp (C) 2.17. 4-Fluorbenz I- 79 300-302 2.18. 3,4-Difluorbenz I- 62 290-292 2.19. 3-P rid Imeth I- 82 >300 Step 3: Synthesis of the alkylated triazolopyrimidine derivatives (5) and (121:

RwN I N
N' _ N NH2 R~N~ N NH2 s~N s~N
R R
(5) (12) General method:
66 mMol of the relevant 7-amino-1,2,4-triazolo[1,5-a]pyrimidin-5-one (4) are ~o dissolved in 10 - 20 times the quantity of anhydrous dimethylformamide and mixed with 76 mMol of potassium carbonate and 76 mMol of the desired alkyl iodide.
The reaction mixture is stirred at ambient temperature for one 1 - 2 days and evaporated to dryness. The residue is stirred with water and methylene chloride. In many cases, after this treatment, compound (5) can be filtered off as a solid and isolated in this ~5 way. The isomer (12) can then be obtained from the filtrate as described below. If no solid is obtained during stirring or in order to isolate compound (12) from the filtrate, the phases of the filtrate are separated, the aqueous phase is extracted with methylene chloride and the combined organic phases are dried over magnesium sulphate and evaporated to dryness. Compound (5) and optionally (12) are isolated 2o by chromatographic purification of the residue. The alkyl halides required R'-X
(wherein R' = R4, RS) are commercially obtainable or may be prepared by methods known from the literature.
Using this method the following substances were prepared:

Table 3:
No. R6 R4 R5 Yield Mp (C) (%) 3.1 -H -Meth I - 80 310 Decom .

3.2 -H -n-Pro - 58 184 - 186 I

3.3 -H - -n-Pro 18 183 I

3.4 -Meth I -n-Pro - 61 228 I

3.5 -Eth I -n-Pro - 65 194 I

3.6 -n-Pro I -n-Pro - 69 170 I

3.7 -i-Propyl -n-Propyl - 50 138 3.8 -But I -n-Pro - 62 167 I

3.9 -t-But I -n-Pro - 64 164 - 165 I

3.10 2-Fu I- -n-Pro - 45 260 - 262 I

3.11 C clo ent I- -n-Pro - 64 148 - 150 I

3.12 C clo ent I- - -n-Pro 22 173 I

3.13 Benz I- -n-Pro - 60 208 I

3.14 Benz I- -Meth I - 52 296 3.15 Benzyl- -Ethyl - 58 213 3.16 Benz I -i-Pro - 29 232 I

3.17 Benz I- -n-But - 55 175 I

3.18 Benz I- -Pent I - 63 188 3.19 Benz I- Benz I- - 51 180 - 181 3.20 Phen I- -n-Pro - 30 270 - 271 I

3.21 C clohex Imeth I- -Eth I - 67 210-212 3.22 2-Phen leth I- -Eth I - 29 173-174 3.23 (4-Me0-Ph)-0-CH2- -Ethyl - 58 177-180 3.24 (4-Me0-Ph)-CH2-O-CH2--Eth I - 100 -3.25 (4-PhCH2-O-Ph)-CH2- -Eth I - 63 240-242 3.26 4-Fluorobenz I- -Eth I - 53 -3.27 3,4-Difluorobenz -Eth I - 61 228 I-3.28 3-P rid Imeth I- -Eth I - 94 186-188 *Isomer separation in following step Step 4: Synthesis of the nitroso compounds (6) and (13) R~ N NO N NO
N ~ N NH2 R5-N N NH2 s~N s~N
R R
(6) (13) General methods (alternative A):
0 10 mMol of 7-amino-1,2,4-triazolo[1,5-a]pyrimidin-5-one (4), (5) or (12) are dissolved or suspended in 10-30 ml of anhydrous dimethylformamide and the mixture is cooled to -5°C. 20 mMol of isoamyl nitrite are added in such a way that the temperature does not rise above 0°C and the mixture is stirred at this temperature for 4 - 24 hours, then as necessary at ambient temperature until the reaction is complete. The ~5 solvent is eliminated in vacuo, the residue is stirred with ether, filtered off, washed with water and dried in vacuo.
The following substances were prepared by this method:
2o Table 4a:
No. R6 R4 R5 Yield M C
%

4.1 -H -H - 85 >350 4.2 -H -Methyl - 79 248 4.3 -H -n-Propyl- 81 211 Decom .

4.4 -Methyl -n-Propyl- 88 226 Decom .

4.5 -Eth I -n-Pro - 94 190 I

4.6 -n-Propyl -n-Propyl- 96 206 Decom .

4.7 -i-Propyl -n-Propyl- 72 210 Decom .

No. R6 R4 R5 Yield Mp (~C) (%) 4.8 -n-Butyl -n-Propyl- g5 196 Decom .

4.9 -t-Butyl -n-Propyl- g3 200 Decom .

4.10 2-Fu I- -n-Pro - g5 261 I

4.11 Cyclopentyl- -n-Propyl- g7 224 Decom .

4.12 Cyclopentyl- -H - gg 225 Decom .

4.13 Benzyl- -H - g7 238 Decom .

4.14 Benzyl- -n-Propyl- g5 208 Decom .

4.15 Benzyl- -Methyl - g6 233 (Decomp.
) 4.16 Benzyl- -Ethyl - g7 226 Decom .

4.17 Benzyl -i-Propyl- gg 190 Decom .

4.18 Benz I- -n-But - g3 196 I

4.19 Benzyl- -n-Pentyl- 74 190 Decom .

4.20 Benz I- Benz I- - g6 236 4.21 Phenyl- -n-Propyl- g2 257 - 258 Decom .

4.22 -H - -n-Propyl63 206 (Decomp.
) 4.23 C clo ent I- - -n-Pro 74 146 I

4.24 C clohe Imeth I- -Eth I - g3 208-209 4.25 2-Phen leth I- -Eth I - g0 200-201 4.26 (4-Me0-Ph)-O-CH2- -Eth I - g3 214-216 4.27 (4-Me0-Ph)-CH2-O-CH2--Eth I - 56 156-158 4.28 (4-PhCH2-O-Ph)-CH2- -Ethyl - g7 201 Decom .

4.29 4-Fluorobenz I- -Eth I - gg 241-242 4.30 3,4-Difluorobenzyl- -Ethyl - g7 234-236 4.31 3-P rid Imeth I- -Eth I - 44 229 General method alternative B):
20 mMol of 7-amino-1,2,4-triazolo[1,5-a]pyrimidin-5-one (4), (5) or (12) are susperided in 80 to 100 ml of glacial acetic acid. The mixture is heated to 70°C, mixed with a solution of 20 mMol of sodium nitrite in 2-4 ml of H20 and stirred for 0.5-2 hours at 70°C, then for a further 0.5-2 hours at 10°C. The product is filtered off, washed and dried in vacuo. Using this process the following compounds were s prepared:
Table 4b:
No. R6 R4 R5 Yield Mp (C) (%) 4.32 Benzyl- -H - 65 236 (Decomp.) Step 5: Synthesis of the diamines (7) and (141:
O O
Rv N NH2 N NH2 N ~ N NH2 RS~N N °NH2 s~N s~N
'o R R
(7) (14) General method (alternative A):
12.7 mMol of the nitroso compound (6) or (13) are suspended in 86 ml of H20 with stirring and 4.9 g (2.9 mMol) of Na2S204 are added. The suspension is heated to 15 80°C and within 30 minutes 15 ml of 50% H2S04 are added. The mixture is refluxed until the reaction is complete. After cooling, the product is usually obtained as a hemisulphate. If no solid is precipitated, the mixture is neutralised with 30%
sodium hydroxide solution and the free base precipitated is filtered off.
2o General method (alternative B):
11.5 mMol of nitroso compound (6) or (13) are added to a mixture of 175 ml of 25%
aqueous ammonia and 36 ml of ethanol, with stirring. Then the mixture is stirred at 30°C until the nitroso compound has substantially dissolved, a solution of 6.1 g (34.7 mMol) of Na2S20a in 57 ml of H20 is added dropwise and stirring is continued 25 for a further 1.5 to 3 hours at ambient temperature. If some starting compound is still present, 10% of the above quantity of Na2S204 are added and stirring is continued until the reaction is complete. The product is isolated by filtering.
The compounds described in Table 5, inter alia, were prepared by one of these so methods (A or B, see Table 5):

.-.

Q

00 N O N f' fl- O V ~ '~ ~ ~ M ~ 00 ~fi~ N M f~ 00 U ~ 1 m O O d0 ~ O ~ N ~ ~t N N N
00 (~ ~ d' O O

~ ~ r- r- e- ~- N
N
N

p N O N O
O v- l 1 1 1 i 1 1 1 ~ ~ 1 v-p- 1 (~ ~ ~ (~

N O N O
Z Z Z Z

\
M ~ tn O a0 N N ~ O ~t QO ~ O N O
f~ CO O f' f' 00 tn f' O f~ ~ I~ (p L

1 1 1 1 1 1 1 1 i 1 1 1 1 1 1 s O O O O O O O = O O O O

C ~ C C C C C ~ C C
1 1 1 1 1 1 1 1 / a 1 Q Q _>'~ C
Z Z Z -~ -p ~ O ~ p O O v N N N
.r ~ Q Q. p 1 1 1 ~ ~ ~ ~ m m O O LL N ~ p U U

p ~ N M ~ ~ (flI~ 00 O O ~ N M d' Z ~ ~ lI7tn lf7~ l(7In lI7~j ~ tI~tf~l!~In lf7 N
ca H

C

_ ~ O d' O ~ (O O ~ N O
O ~ O ~ N ~"~O N ~ CflO ~ M ~ O r- 00 Q U N N N ~ N ~ ~ N N
O ~ , ~ , ~ ~ , ~ , , , y 7 , , , O O r- ~ ~ OD N N N ~ ~ O t~ M ~ O O
._ N N N ~ N ~ ~ N N

N N N

O ~ ~ O
~ , O , ~ , , , , , , , , , , (a (n N N N

Z Z Z

\
tI~00 N I' O O ~ Cfl~' ~' CO 00 ~ 00 ~I7N
.C O ~ O d' 00 I~ 00 00 07 O 00 00 00 OD O a0 L

a a m a m a a a m m m m m m m m O O
m , , , , , ~ ~ , , , , , , , , , , , , a .,..m ~ N ~ o o ~ .~ ~ L ..Ct L L
~ ~ ....-.....,...~. ..~.,-W ~ N ~ uJ W uJ W uJ uJ uJ uJ
C m C
, , , N , , Z N

N ' C =

J , , ~ ' U O V ~, >' (fl , , i i , ! = >, ~, >, ~ U
N N N N N C ~ Q ~ ' y..
N N N O N L O O N ~ ~ L
m m m m m 0.. ~ 0 .~ ~ ~ = O

U ~ a ~ ' U c~iM
O '~t' U N ~ ~ ~

, CO I' 00 W O ~ N M ~f'~ CO 1~ OD O O O

O ~ ~- r- ~ N N N N N N N N N N M M

tt7~ ~ ~ ~ ~ tf~~ ~ ~ ~ ~I7~f7~ ~t7 Stea 6: Synthesis of amides (81 and (151:

Rv N NHCOR2 N NHCOR2 N N NH2 RS~N N NH2 s~N s/ N
R R
+ +

Rv N NH2 N NHZ
N N NHCOR2 R=N N NHCOR2 s N s N .
R R

(8) (15) General method (alternative A):
~0 30 mMol of diamino compound (7) or (14) are suspended in 165 ml of anhydrous dimethylformamide and mixed with 45 mMol (or in the case of hemisulphates 78 mMol) of 4-dimethylaminopyridine. The mixture is stirred for 30 minutes at ambient temperature, cooled to 5 - 10°C and a solution of 39 mMol of the desired carboxylic acid chloride in 16 ml of anhydrous dimethylformamide is added.
Then the mixture is stirred for 2 hours at 10°C and overnight at ambient temperature, after which the solvent is eliminated in vacuo. The residue is added to water, the solid is filtered off and washed and optionally purified by recrystallisation or chromatography.
The carboxylic acid chlorides required are commercially available or may be 2o prepared by methods known from the literature.
Using this method the compounds of formulae (8) and (15) described in Table 6a were prepared, inter alias p U Cfl00 N ODO O ~ O 00 M O ~ M O N I W
N O 1~ O O O 1 ~ O O ~ I'O O '~tCfl1 1 1 I N M

Q 0 M r ~ N N N N N ~ ~ ~ N N ~ ~ N N

N

M

N

M tnu7 u7 ~ N t'O 00 ~ r- COO CO O CO d'M r- O O ~

00 M CO O I~.f~ t~O CO 00f' COCO I~ I~t~ t~1' ~ O CO CO

N

_ I I

i O C

_i _I _I_I _I N _t _I_I _I _I _I
~r , 1 w--~r--i.1-r- .a-~I ~ ~ ~ .L..i- >,i rt-~- w-w-n-~
N C - - C C C C - N C C C - C O C
O N N O N N ~ N O ~ N N N ~ ~ N N ~ N N
O ~ ~ O O O ~,O L ~ O O O W O ~ O (iJO O
U m m U U U j U a ~ U U U 1 ~1m U 1 U U
U U U U I U ~ U U U U U U

c~

co - - -O O O O O O O O O O O O O O O O Z

1 I I 1 1 1 1 I I 1 1 1 1 I 1 1 m !' C C O C C C C C C O C O C C C

_ ~ _ 1 I 1 I I 1 r ~

.~,.,_ ~ ~ ~ - - - - -d' Z Z Z Z ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ Q ~ ~ ~ N N N N
I I I 1 ~ LIJt1Jd- a a p-,mlm, O O O LLLL ~ N N N
I I 1 C C C 1 O,''iU U U N

U U U

i~

M r- N M d: tnCflf'CO O O r' N M V In(D f'00 O O ~ N
O O ~ ~ ~ c- r- ~ r- ~ ~ ~ N N N
Z (flCOCflCO CO(flcflCO CO ~ CO COCO CO COC~ C~CO CO COC~ C~

(15 H

00 O CO f~ N O t~ tI~f~
p M M CO N ~ O M N ~ ~ 00 M ~ Cfl~ N N ('O~~ ~ 00 N 00Cfl~ ~ I~ COCO ~ '~TN O ~ ~ ~ ~ ~ ~ N
N ~ ~ ~ a0~ ~ ~ u7M N N N O ~ COu~ M cflN
O OD C~n 00 M f~O COo0 N ~ r- ~- N N M

\

M ~ ~ N 00 O 1' O I' f~00 07 O tn 00CO ~ N O M ~

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~ O O O O O uJO O ~ a ~ U ~ ~ LL _O LL
N ~ p U U U U U U U , , , a N U
~ U U U U U U U N ~ M U U

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, , , , ~ , , , , , , , _,_, , _, _,~ _, _,_, ........

CON N N N N _ _ _ _ C C = N N N N N N N ~ ~ p C C C C C N N N N O N , O C C O C O O
O O O O O C O O C t ~ O O O O O O O ~ ~ , O O O O d.d m m m m m m m ~t-~~ N
m , , M M

M Wit'~ Cfl1' 00W O ~ N M d' t0CO i'00 O O ~- N M d' O N N N N N N N M M M M M M M C'~M M d'~ d'~

O O c0O CO CflCO CflCO O O CO C~CO COCO O M (O CflCO (fl f~ 00 M CO O OD 'd' 00 CO 00 ~ I' U O O d0 ~f7 00 O C~ 1' M O N M
O N ~ c- ~- r- M ~ ~ ~ O N N
i i i i ~ i i i ~ O i i i ~ a i i a i CO N tn O (fl O GO M ~ (fl N Wit' C O O 00 ~ f~ O CO ~ M O N M
G N r r r r- M ~ ~ ~ N N
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r- O In ~ In c- M CO ~ (~ 00 N M tn ~ O O ~ O
_ 00 f~ O o0 (fl d' O f~ O 00 O O ~ f~ O ~ ~ a0 f' N_ i O
i i (0 ~ i i ~ ~ i - - - - - - - -i - C - C 0 C - ~ C C C ~ N
N L O L O ~ N L N O O
O ~j J O ~ O (iJ O O O O ' O
U ' U ~ U ' U U U - U ~ - U
U U ~ U U U U U ''-' " U
H
M
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(O
s i ~ a ~ i ~f L L ~ .C 0 ~ L L L L ~ L L L L L S L L
.r ..... ~. rt.. .r r-. .... ..r ... .r .-. .-. ..r .... ..-. .-. .r W W LLJ LLJ ~ ~ W W LJJ W LJJ W W W W W L!J W LJJ
i i i i ~ ~ i i i i i i i i i i i i i N
i N N N
U I
.t~,~_~_~VUpU~ --O O N .~ ~ C c c c .... .r ~ N O N N
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U U ~ ~ N a. V V' ~ V' ~ M M M
CO f~ OD O O r- N M ~ tc~ CO I' 00 ~ O t- N M
O 'd' ~ ~ ~ d' ~ ~ ~ tn ~ ~ ~n ~n ~ u7 c0 O CO O
z M c~ Cfl c0 cfl c0 cfl cfl c~ (fl cfl cfl c0 c0 c0 c0 CO Cfl CO

General procedure (alternative B):
6.6 mMol .of a diamine (7) or (14) are suspended with 7.3 mol of the corresponding carboxylic acid in 15-25 ml of acetonitrile. 7.3 mMol of N-methylmorpholine are slowly added with stirring. Then a solution of 7.3 mMol of isobutyl chloroformate in 6-7 ml of acetonitrile is added dropwise at 20-25°C within 10-20 minutes. The suspension obtained is stirred for 4-6 hours at ambient temperature. For processing, the suspension is filtered and washed with acetonitrile. The resulting filtrate is concentrated and chromatographed over silica gel.
o Using this process, the compounds of formula (8) and (15) described in Table 6b were prepared:
Table 6b:
No. R6 R4 R5 R2 ' Yield in 6.64 4-fluorobenzyl-Ethyl- - ~ 26 Step 7: Reactions of cyclisation to obtain the imidazotriazolopyrimidines (9) and 16 R~
N I N~ R2 N I N~ R2 N~ N N R-~N~ N N
s~N s~N
R R
20 (9) (16) General method (Method A, alternative A):
14.4 mMol of (8) or (15) are suspended in 75.5 ml of H20 and 37.8 ml of ethanol and refluxed with 17.4 ml of 50% NaOH and 4.82 g (65 mMol) of Ca(OH)2 for 24 hours.
25 The mixture is allowed to cool, made acidic, the solid is filtered off and dried. The product is optionally purified by recrystallisation or chromatography.
Using this process the compounds of general formulae (9) and (16) described in Table 7a were prepared, inter alia.

M '~ ~ c- 00 O
O ~ CON O N M O CO r-N COO N N M ~ V ~ O N
O 1 ~ I ~ N tn O N t ~ ~ t 1 M N O N ~
~ M N N ~ N N N Q N ~ N M ~ ~ N D D O N N

OM n M N

\

a O tI~00 O N 00 00~ O ~ N N ~ tn CflO ~ '~tO M O
00 M CO ~ CO~ COf~ ~ O C~ f~CO 00 ~ I~ CO'~ ~ ~ CO

N_ t C

I I I i I _ I t I I I I

_ _ _ _ _ I N _ _ _ t _ _ _ N C - - C w-.n~ - ~ - O ~ ~ ~ - 7,- ~ - .~ +~'~
O N N O C C L C O ~ C C C ~ ~ N C .C C C
N N N O O O O p p p O ~ ~ O O O [jJO ~ p O O O [j~ ~ O [j O O
U m m U U U I U a p U U U I ~ m U JJ U U (~
t U U U U U ~ U U U U U U N

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1 1 1 1 I t I I t I I i t I 1 I I 1 1 I I

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O O O O O O O O O O O O O O O O N
Z L L L L L L L L L L L L L L L L I

I O C C O O C O C C C C C C C C C

1 1 1 1 1 I 1 1 1 1 I I 1 1 1 t _ -~ 1 1 1 I 1 - - -O Z I I I '''~ ~ OL O O O O ~ N N N ~ ~ N N N
I I I 1 N ~ ~ ~ ~ ~ ~ m m O O _O LLLL ~ N N
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O N N N N O O N M N N N M M N N
M ~ V~ N O 1 ~ 1 1 1 1 (~ 1 I 1 1 I 1 I I
N N M N N ~ N ~ M ~ 0 ~ ~ N ~ O ~ ~ ~ N O M

Cfl M M M r- M C~C~ N 00 ~ M f' N N N N O O N M N N N M M N N

O O

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M I~M M Cflf~ M CO f'00 CO~ ~ d-O N O ~t M N
CON tn~ ~ tn CO tc~~ O f' M ~j ~ I~CO CO ~- f't0 N

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1 I I I 1 1 1 I , 1 I

1 1 t -- r-r~ ~ ~ -N .~ ~ .t.I- X ~ 1 1 O N ~ ~ ~ N uJN LL W _O
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N N N N N N N N N N C C = = N N ~ ~ ~ N X X

N N N N N N N O N N L L N N 'O -O_~ N N N
m m m m ~ d. m m ~~ ~L-N m Q O

U _ U

M M U U

N c'~'~ttnCflI~00 O O ~ N M ~ ltdCO I'OD 07O r- N M

O N N N N N N N N M M M M M M M M M M ~ ~t ~ '~t z I~f~ N I~f~ N N N N f~ N f~ !~N N N I~ f~f~ I~ I~h M ~ O 00 CO ~t ~ O f~ O ~ N M
U 00 O O O M tI7 C~ M N CO
O N N N M ~ N N ~ N N M M N M M M
i ~ ~ N ~ pp tn ~ ~ ~ ~ i ~ i N N O Cfl N vt ~ N N N f~ ~ ~' ~c7 O O
00 O7 00 O M ~ Cfl M N (O r- N M
N N N M N N N M M N M M M
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N L O O ~ N N O N m O
O ~ O uJ O O O O .C _O
U ~ U ' U U U U O V
U ~ U U U U U ' U
M
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i ~ i i o ~ i ~ s i ~ ~ i i t .~ O O .~ L L ~ L L t L L L
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i i i i i ~ ~ i ~ i i C C
i N
N N U N
IZ 'U-''-' ~ a Nr~ >, U U ~, ~ N N N N
NN~~O'O'Z~ NNN N
N N ~ ~ i .Q ~ ~ ~ 0 ~ N
ONOOa~UO OOO O _~~ N
ate. ~ U ~ ~ a- V ~ ~ ~ ~ D D ~ .>' a N V V ~ ~ ~ a ~ v v ~ d' ~ c~
cYi c~
mn co ~ ao 0 0 ~ N M mn c~ ~ ao 0 o ~ ~ ~ ~ ~t m mn m mn m ~n Z r~ ~ t~ ~ r~ r~ t~ ~ t~ r~ t~ t~ r~ t~ ~ r~

General method (Method A, alternative 4 mMol of an amide (8) or (15) are stirred in 10-15 ml of tetrahydrofuran and 25-35 ml of H20 with 46 mMol of lithium hydroxide monohydrate at 45-65° for 14 days. Then the mixture is acidified with 6 N hydrochloric acid and suction filtered. The crude product is recrystallised from methanol. The resulting product is separated by chromatography on a silica gel column.
The compounds of general formula (9) described in Table 7b were prepared by this method.
Table 7b:
No. R6 1 R4 R2 Yield Mp (oC) (%) 7.62 Cyclohexylmethyl-Ethyl- ~ ~ ~ 10 246-248 ~~

7.63 Cyclohexylmethyl-Ethyl- ~ 3 258-260(Decomp.) General method (Method B~:
10.1 mMol of (7) or (14) are stirred into 34 ml of formamide for 1.5 hours at 200°C.
The remaining formamide is distilled off in vacuo and the residue is stirred with water.
The solid is filtered off, washed with water and the product is purified by recrystallisation or chromatography.
Using this process, the compounds (9) and (16) listed in Table 7c were prepared:
Table 7c:
No. R6 R4 R5 R2 Yield Mp (C) 7.64-Ethyl -n-Propyl- -H 84 >300 7.65C clo ent I- -H - -H 53 215 7.66C clo ent I- -Meth - -H 7 >300 I

7.673-P rid Imeth -Eth I - -H 58 328-330 I-7.68C clo ent I- -n-Pro - -H 58 287 Decom .
I

7.692-Fu I- -n-Pro - -H 74 >300 Decom .
I

7.70Benz I- -Meth - -H 9 >300 I

7.71Benzyl- -n-Propyl- -H 75 >300 7.72~ Benz I- -i-Pro - -H 90 >300 I

No. R6 R4 R5 R2 Yield Mp (C) 7.73 Benz I- -n-But - -H 75 >300 I

7.74 Benz I- -H - -H 63 >300 7.75 Phenyl- -n-Propyl- -H 75 295-296 (Decomp.

7.76 Cyclopentyl- - -n- -H 35 202-203 Pro I

7.77 3-P rid Imeth -Eth I - -H 58 328-330 I-7.78 C clohex Imeth-Eth I - -H 87 328-330 I-7.79 2-Phen leth -Eth I - -H 84 273 I-General method (Method C):
At 0°C, 0.66 ml (7.2 mMol) of phosphorusoxychloride are added to a solution of 6.8 mMol of the desired N-formylamine in 6 ml of diglyme. The mixture is stirred for 30 minutes in an ice bath and then 4.8 mMol of nitroso compound (6) or (13) are added. The mixture is stirred at 80°C for 30 - 60 minutes and added to ice water, the solid product is filtered off, washed and dried. The product is purified by crystallisation or by chromatography.
Using this process, compounds (9) described in Table 7d were prepared:
Table 7d:
No. R6 R4 R2 Yield (%) Mp (C) 7.80Benz -n-Pro N-Mor holin I- 21 298 I- I

7.81Benz -n-Pro 4-Benz I-1- i erazin21 266-268 I- I I-7.82Benz -n-Pro Dimeth lamino- 9 272-274 I- I

7.83Benz -n-Pro N-Pi eridin I- 22 294-297 I- I

The formylamines required are prepared by methods known from the literature by reacting the amines with 88% formic acid and acetic anhydride.

Step 8: Reactions of alkylation General method (alternative A):
4 mMol of imidazo[4.5-eJ-s-triazolo[1,5-a]pyrimidin-5-one unsubstituted -in the 3- and 4-position [(9) with R4 = H; (16) with RS = HJ are taken up in 26 ml of anhydrous dimethylformamide and mixed first with a solution of 0.1 g (4.2 mMol) of sodium in 4 ml of anhydrous ethanol, then with 4.2 mMol of the desired alkyliodide. The mixture is stirred overnight at ambient temperature and then evaporated to dryness.
The residue is dissolved in 2 N of NaOH, the solution is washed with toluene and o then adjusted to pH 6. The solid precipitated is filtered off and purified by chromatography. If required, the dialkylation products (la) and (Ib) may be isolated.
The following compounds (9) were prepared using this method:
~5 Table 8a:
No. R6 R4 R5 R2 Yield Mp (C) . (%) 8.1 Benz I- -Meth - -H 9 >300 I

8.2 C clo ent -Meth - -H 7 >300 I- I

8.3 -H -Meth - C clo ent 44 285 I I-8.4 -H -Eth - C clo ent 57 249-253 I I-8.5 -H -n-Pro - C clo ent 52 255 I I-8.6 -H -n-But - C clo ent 45 243 I I-8.7 -H -t-Butyl- Cyclopentyl-10 190-191 8.8 Benz I- -Eth - -t-But I 24 243-244 I

8.9 Benz I- -Eth - Phen I- 24 343-345 I

8.10 -H -n-But - C clo ent 45 .. 243 I I-8.11 -H - -t-But C clo ent 4 149-150 I I-Moreover, the following compounds (la) and (Ib) could be obtained by this method:
0 R~ 0 4 ~ 4 RwN I N~R2 RwN I N~RZ
N~ N N N~ N N
6~=N (la) 6~=N Rs (Ib) 2o R R

Table 8b:
No R6 R4 R1 or R2 Yield Mp (C) R3 (%) 8.12 Benz I- -Eth -Eth -H 4 >300 I I

8.13 -H -Meth -Meth C clo ent 4 206 8.14 C clo ent -n-Pro -n-Pro -H 10 146 I- I I

8.15 C clo ent -n-Pro -n-Pro -H 5 151 I- I I

8.16 Benz I- -Eth -Eth 2-Fu I- 16 187-189 I I

General method (alternative B):
20.4 mMol of imidazo[4.5-e]-s-triazolo[1,5-a]pyrimidin-5-one unsubstituted in the S-and 4-position [(9) with R4 = H; (16) with R5 = H] are stirred together with 40.8 mMol of potassium carbonate and 40.8 mMol of tert.-butylbromide in 100 ml of anhydrous dimethylformamide at 70°C for 7 days. The mixture is evaporated to dryness, the o residue is combined with 100 ml of 2N NaOH, the aqueous phase is washed thoroughly with toluene and neutralised. The precipitate is filtered off, extracted with CH2C12/CH30H 9:1 and the extract is evaporated down. The isomeric alkylation products (9) and (16) are isolated by chromatography on silica gel with CH2C12/CH30H 95:5 (Table 8c). The following compounds were prepared using this ~5 method.
Table 8c:
No. R6 R4 R5 R2 Yield Mp (oC) 8.17 -H -t-But - C clo ent 10 190-191 I I-8.18 -H - -t-But C clo ent 5 149-150 I I-2o General method (alternative C):
0.05 Mol of starting compound (9) are dissolved in 500 ml of absolute dimethylformamide and stirred with 0.055 Mol of potassium carbonate and 0.055 Mol of benzyl bromide overnight at ambient temperature. For processing, the solvent is distilled off in vacuo and the residue is taken up in methylene chloride/water. The 25 organic phase is separated off, washed once with water, dried over magnesium sulphate and evaporated down. The residue is crystallised with ether. The compounds (la/lb) thus obtained are listed in Table 8d.

Table 8d: .
No. R6 R4 R1 or R2 Yield Mp (oC) R3 (%) g.1 (4-Me0-Ph)-CH2-O-CH2-Eth Benz C clo ent 85 127-128 g I- 1- I-8.20 (4-PhCH20-Ph)-CH2- Eth Benz C clo ent 66 138-140 I- I- I-IX. Functionalisation of the imidazotriazolopyrimidines of general formula (I):
IX.a. Deblockinct of imidazotriazolopyrimidines (la/lb) with protected hydroxyl functions:
General diagram of synthesis taking as example the compounds of general (formula Ib):
O ' O

R\N N Rz ~~ R\N N z I I ~~-- R
//\N N ~N N
N ~ R3 N ~ s Me0 ~ ~ -N -N R
O HO
DDQ: 2,3-Dichloro-5,6-dicyano-benzoquinone The above reaction was carried out using a method known from the literature ~5 (Tetrahedron 1986, 42, 3021 ). The following compounds were obtained, inter alias Table 9:
No. R6 R4 R1 or R2 Yield Mp (oC) R3 (%) g.1 HO-CH2- Ethyl-Benzyl- Cyclopentyl-97 204-207 IX.b. Deblocking of imidazotriazolopyrimidines (la)/(Ib) with protected amine functions in the side chain:
General diagram of synthesis taking as example the compounds of general formula (Ib):
O O
RAN N /~ Hz RAN N /~
N N --~ ~ I >- N N H
N / N ~/ _ Cat. / N ~J
-N R3 ~ ~ N ~-.N R
s/
R R
0.83 mMol of a 7-(4-N-benzyl-1-piperazinyl)-imidazo(4.5-a]-s-triazolo[1,5-a]pyrimidin-5-one are taken up in 30 ml of glacial acetic acid and hydrogenated at 60°C and at 5 bar for 6 hours in the presence of 0.1 g of 10% Pd on charcoal. The catalyst is 1o filtered off, the residue is evaporated to dryness and stirred with CH30H, the solid product is filtered off, washed and dried. Using this method the following was obtained:
Table 10:
No. R6 R4 R1 or R2 YieldSalt formMp (oC) 10.1Benzyl- n-Propyl-H- 1-Piperazinyl-53 Acetate 260 IX.c. Cleaving of protective amine groups from the imidazotriazoloavrimidinone core structure:
General diagram of synthesis taking as example the compounds of general formula (Ib):

N N
R\N ~ z H2 R\N z -- R ~ ~ ~~- R
N N ~N N
H
N -N / ~ N -N
s~ ~ s~
2o R R
7-N-benzylated imidazotriazolopyrimidines of general formula (I) are dissolved in methanol or absolute glacial acetic acid and hydrogenated under a hydrogen atmosphere (1-5 bar) at 25-80°C with the help of a palladium catalyst (e.g: Pd/C) over a period of 2.5-40 hours. The catalyst is filtered off, the filtrate is evaporated down and the residue is purified over silica gel. The purified product is crystallised from the eluate, preferably with ether and then, if possible, crystallised as a salt (preferably methanesulphonate). In this way the following compounds were obtained.
Table 11:
No. R6 R4 R2 Salt formYield Mp (C) 11.1 Methox meth I- Eth C clo ent - 27 246-248 I- I-11.2 Ethox meth I- Eth C clo ent - 45 224-225 I- I-11.3 H drox meth I- Eth C clo ent - 37 305-307 I- I-11.4 Benzo lox meth Eth C clo ent - 54 238-239 I- I- I-11.5 Dimethylaminomethyl-Ethyl-Cyclopentyl-Methanes 29 224-225 ulfonate 11.6 N-Morpholinyl-methyl-Ethyl-Cyclopentyl-Methanes 47 184 ulfonate 11.7 Phenox meth I- Eth C clo ent - 40 229 I- I-IX.d. Alkylation of hydroxy-substituted imidazotriazolopyrimidinone:
General diagram of synthesis taking as example the compounds of general formula ~o (Ib):
O O
R\N N z R\N N 2 \~. R NaH I R
N N alk Ihalide ~ N N
R y N -N Rs s' HO R
3 mMol of hydroxyalkyl- or hydroxyaryl-substituted imidazotriazolopyrimidines of general formula (la), (Ib), (Ic) or (Id) are dissolved in 30 ml of anhydrous dimethylformamide, mixed with 3.6 mMol of sodium hydride (60% suspension in mineral oil), stirred for 1 hour at ambient temperature, mixed with 3.6 mMol of alkyliodide and stirred for 1-2 days at 25-60°. To complete the reaction, 50% sodium hydride and alkylhalide are added. For processing, the reaction mixture is evaporated down to leave the residue which is taken up in ethylene chloride and water, acidified with 2N hydrochloric acid, the aqueous phase is extracted once more 2o with methylene chloride, the combined organic phases are washed with saline solution and dried over magnesium sulphate and then evaporated down. The residue is purified over silica gel and the eluate is crystallised from ether.
The following compounds were prepared using this method:
Table 12:
No. R6 R4 R1 or R2 Yield Mp (oC) R3 (%) 12.1Methox meth Eth Benz C clo ent 37 116-118 I- I- I- I-12.2Etho meth Eth Benz C clo ent 36 120-123 IX.e. Acylation of hydroxy-substituted imidazotriazolopyrimidines:
General diagram of synthesis taking as example the compounds of general formula (Ib):
O O
R~ N N R~ N N
\~ R2 pyridine ~ \ R2 N N carboxylic acid / N N
N -N Rs chloride N -N Rs s HO R
The hydroxyl compound is taken up in pyridine and, whilst it is being cooled with ice, stoichiometric quantities of acid chloride are added. When conversion is complete the mixture is added to ice water and acidified with 2N hydrochloric acid. The aqueous phase is extracted several times with methylene chloride. The combined organic phases are washed with saline solution, dried over magnesium sulphate and 2o evaporated down. The residue is purified over silica gel and the eluate is crystallised from ether.
The following compounds were prepared by this method:

Table 13:
No. R6 R4 R1 or R2 Yield R3 (%) 12.1 ~ Ethyl- Benzyl- Cyclopentyl-73 O-CHZ

12.2 ~-~ ~ Ethyl- Benzyl- Cyclopentyl-93 N O-CHZ

IX.f. Haloaenation of hydroxy-substituted imidazotriazolopyrimidines:
General diagram of synthesis taking as example the compounds of general formula (Ib):

R~ N halogenating R~ N
N ~ ~~ R2 m~ N . ~ ~ R2 N N NEt3 ~ N N
N-N Rs N-~ Rs s~
HO R
The hydroxylated imidazotriazolopyrimidines are converted into the corresponding o halides in the usual way with halogenating reagents such as SOC12, SOBr2, POC13 in inert solvents in the presence of bases (e.g. NEt3).
The following compounds were prepared analogously:
~5 Table 14:
No. R6 R4 R1 or R2 Yield Mp (oC) R3 (%) 14.1 Br-CH2- Ethyl- Benzyl- Cyclopentyl-66 188-189 IX.g. Nucleophilic substitution in halogen-substituted imidazotriazolopyrimidines:
General diagram of synthesis taking as example the compounds of general formula (Ib):
O alcohol O
R~ N or R~ N
N ~ ~~ R2 amin; N ~ ~~ R2 N N Base ~ N N
N -N Rs N -N Rs s~
X X: chlorine, bromine, R
iodine Using generally known standard procedures, halogen-substituted imidazotriazolopyrimidinone derivatives may be converted into the corresponding ~o amines and alkyloxy/aryloxy compounds by reacting with nucleophiles (e.g.
alcohols, amines) in the presence of a base. For preparation of the amines, please see the methods of synthesis described for Step 8 hereinbefore. The alkyloxy/aryloxy compound may be synthesised in accordance with the general method under point IX.d. The following compounds were prepared analogously:
Table 15:
No. R6 R4 R1 or R2 Yield Mp (oC) 15.1(CH3)2N-CH2- Ethyl- Benzyl-Cyclopentyl-100 -15.2N-Mor holinometh Eth Benz C clo ent 96 -I- I- I- I-15.3Phen lox meth I- Eth Benz C clo ent 86 155 I- I- I-IX.h. Oxidation of hydroxy-substituted imidazotriazolopyrimidines:
General diagram of synthesis taking as example the compounds of general formula 20 (Ib):
O O

R~ N R~ N
N ~ ~~ R2 Oxidati~ N ~ ~ R2 ~N N ~N N
N -N Rs N -N R3 s' HO R

Using generally known standard procedures (e.g. Tetrahedron Letters 1979, 5, 402) hydroxy-substituted imidazotriazolopyrimidinone derivatives may be converted into imidazotriazolopyrimidines with functionalities of a higher oxidation state (e.g.
aldehydes, carboxylic acids). The following compounds were prepared analogously:
Table 16:
No. R6 R4 R1 or R2 Yield Mp (oC) R3 (%) 16.1-CHO Eth Benz C clo ent 48 153-154 I- I- I-16.2-COOH Eth Benz C clo ent 38 157-158 I- I- I-IX.i. Derivatisation of imidazotriazolopyrimidinone carboxylic acids:
o General diagram of synthesis taking as example the compounds of general formula (Ib):
O O
R~ N R~ N
N ~ ~~ R2 ~ N ~ ~~ RZ
N ~N N
N ~ N Rs N ~ N Rs s~
HO R
O
Using methods known from the literature, imidazotriazolopyrimidinone carboxylic 95 acids may be converted into a plurality of carboxylic acid derivatives (e.g. halides, anhydrides, amides, ester, etc.). The following general method may be used to prepare the corresponding imidazotriazolopyrimidinone-methyl carboxylates:
0.003 mol of imidazotriazolopyrimidinone carboxylic acid are suspended in a 1 molar 2o solution of SOC12 (1.5 eq) in MeOH. The resulting clear solution is stirred at ambient temperature. After the reaction is complete the solvent is distilled off in vacuo and the residue remaining is purified by chromatography on silica gel. Using this process the following were prepared:
25 Table 17:
No. R6 R4 R1 or R2 Yield Mp (oC) 17.1. -COOCH3 Eth Benz C clo ent 71 155-157 I- I- I-IX.k. Reductive amination of imidazotriazolopyrimidinone aldehydes:
General diagram of synthesis taking as example the compounds of general formula (Ib):

R\N N 2 1) amine R\N N z \ R --i \ R
2 red.
/ N N ) ~N N
N -N Rs or H2 N -N Rs s~
H R
O
Using generally known standard procedures, imidazotriazolopyrimidinone aldehydes may be converted into the corresponding amines by reaction with primary or o secondary amines and subsequent reduction or hydrogenation of the Schiff's base formed as an intermediate. The following compounds were prepared accordingly:
Table 18:
No. R6 R4 R1 or R2 Yield Mp (oC) 18.1~ ~ NH-CH2 Ethyl- Benzyl-Cyclopentyl-- -N

, , ~ , , y ~ ~ p N o ~ ui a~ a~
O ~ , O O o N 'r N O d' N
'L ~. c o C ~ ~ C
C (~ N O ~ O N O N O
, O t~ ~ ~ ~ tI~
L (~] tn ~ O ~ ~ I=
'; ~, '; 'T
Q ~ T ~ ~ I=
O
cN0 O ~ a Q d .a Q. Q Q
E C~ C CC C CB . i CO
. ~ C ~ td7 ~ tn ~ N ~ Ln N ~ N O N O N O N O
O ~ C ~ O ~ O ~ O ~ O
m a m ~ m ~ m ~ m c~u N ca N ~ N +''. N ~ N .~L.
U
O ~ O O O O O
O' ~ »-~ O O O O O
.~ o, M M M M M
A /~ A /~ /~
O
-.
O
O N ~ ~ i O
O ~ ~ \I \I \I \I 'I
(o ~~Z,yZ
O
O
c0 Z _Z~
L
Q Z ~~, ~ ci ~ = a i s i Z~
I I
~' L
O O >, Q Q
t6 ~ ~ ~ O ~ O
L i N L m L
N

O
-O

O ~ i ~ ~ ~ i Q
O
U
N
L
u~ O M
Z = = Z Z
i (6 _N
N Q
O O ~ O ~- N M ~?' u7 Ct5 Z
O O X
(B
I- E-' o ' _' ' _' , ~ p N
tW .~ N N N ~ ~E , C ~j, ~E , N CC N O N ;O N C6 N ~ ~ i ~ d 'T
C ~ C ~ C ~p C a T C' ~ ~ j, O O .p O O O Q .- ~ , !Z C
m = o -yn ~ ui .>, a yn n°i ° ~ ~, ~? o .° o N >, c -; c a c ~ c .B o o-.~ ~ ~ Q-,E
' o c E ,n ~ o ~ :a ~,;o_ ° :o c :o c ~ ~, c , ~= c ~ c ~' ~ ~ E °'E nE ~ o ~t a 'N N ~r ,Z
a ~ E o E .~ a~ .~ c - o . In o co ~ ~ - cc o " 'yn ~ Q v a ~ a ~ a c c c ~ o .r T u~
_ Q , ' >. o v ~ cc ~ cc .~ cc ~ m o. ° .°c o .a N c ,r O C Q Q ~ O tn O tO O ~ I~ 47 U C fl. p N N .N O
C .L fl. r' C1 '- Q r' ~, '- >, >, p N c tc~ ~ N
>, O O O O O O j O U O- ~ .O W t N
Z _ 1 L ~ . rtL.i (~ I~ _O V' c6 1' .~ 1\ .~ ~ ~ '~ .~ N c- Z N v CNC d tn i ' N ' ' O ' ~_ ~ ~ , ~.. , r.. , r-. O f~ N I ~ ~ C I ~ N
N .~ N O N N N ~ N N N ~ ~ O
L r'-, 1=, N ~ N ' i C ... c O c p ~ N ~ N ~ N Q ~ C
L m ~ m cN6 m ~ m ~ m ~ m ~ ~ ~ m N O m O .p m N N
U N ~ N ~ N ~ N ~ N ~ N ~ N tn N '00 O N Q E N ~ O
~ C
U
o N ~ ~ ~ ~ N ~ ~ N CEO
N N ~ N M M N N ~ N
N N N N
M / I / I / I / I / I ~ I ~ I ~ I ~ I ~ 1 I
M
M

I
Q Q Q
O O ~ >' O ''-' L L ~ ~ L O ~ OL O O
uJ a m d C C 1 C I, C C C

N ~ ~ ~~~ z~ Z1 C ) CZJ
I z , L
O M Z I I I Z I I Z Z Z
I 1 I 1 I 1 1 t I 1 Cfl I~ 00 ~ ~ r' N M d' tn O Z ~ ~- r- r- ~ c-X

, , , o , , N N O N N
N c0 C ~ ~ ~ ~ N ~ p ca N
a O ;~ N
N
L -c >', .c u~ ~ ~n ~t .~ o ~ o E o E o w >, o- >, ~ ~c ~ o ~, u? y u? ~, u? ~, u?
oQ. 'oQ o »; o N oc ~,c ac c.c ~,cv ~,'° ~ ° '~ ~ a~ ~ ° Q~ o~ °a a~~
~ ~n ~ p -Q o a> ~ o ~ o ~ ~ Q ~ ~ ~ ,?- ~
.: a a W n '° ~ ' ~= ' ~t >, c ~, ' >, ~ >, a~ o a> o ' ~ , ~ ' ~ 'n ~, 'n . a. ~ ~ r;' n. d' fl.
»; o -; o >, ~ o ~ c ~ c >, cNO v cNC c ~ ~ c ~ ;~ o ~° Wn ~, a c a c a ° o a~ ~ ~ ~ a~ s a .~
>, ~ ~, ~ ° ~, E_ ~ ~. ~, ~ ~, ~ o ~ o p o 0 0 w ..'C.. J, .-O,- i ~ !Z s f~ ~ Q , p U p U O
N ~ N ~ U ~ ~ ~ ~ fC ~ c6 ~ N ~ N V N V N
t~ ~'. t!7 ~ ta7 C E C ~j C ~ C ~ C ~ N ~ I~ C
n ~ ~ ~ , N 'C U N N ~. N r... , "r V ~, ~, ~ ~ tZ 7, !? ~ Q.~ Q ~ O- ' , , NO NO N_O _O fl. Op OO p C ~ C ~ C O U (B U ~ U Q U ~ U ~ C ~ C
N N ..p N ~ N N ~ ~ ~ N ~' N ~' W"
.!' m ° m ° m c>3 U ~? U c6 U m U ~ U 'n C , ~ C , ~L , , ~' , ~L , .~ , ~; , ~
U N . O N . O N ~. N N .r N .,.r N N I~ N
O
~ C p ~ ~ ('O
'-'CU('~~N~Or~0~00NNmN
° N N N ~ N ~ N ~ ~ ~ N
D p N N N
\I \I \I
~I

II II
Q' L L _ _ _ _ _ _ _ O O
O O O O
L ~ ~ ...
1 ~ ~ I 1 1 1 ~ I I 1 1 I

O
U W
L
O
I I Z I Z Z I I I I

C) ~ ~ ~ ~ C) r r' ~ ~ ~ N N N N N N
X
W

1 1 , co ' ~ '° ' a~ 0 0 . c o N
o~o ~ ~°'>,~o~c~ua~
v~ o ~ ' In s ~°- ~ ~ ;~ c u~ay:~E~;';~~~o .c yn o ~ .>, ~, .c ~, . ~ ~n o ~ N ' p- o .° °,~ >, c ~n ~ o o ° .-cuv o .~ ~ L ~ ~ Q a O ~ ~_ c N C C ~ ~ci N C ~ C ~ ~ O ~ O ~ O O ~ 'ct N C 7, O O .~ O ~_ ~ ~ N ~ ~; >, ~ O _I p rp ~ Q
.c~ ~ ~n ° o s c ~' c o c ~. o >' ~? :° c 't cu -, , N c »..a >,~ L~ U N ~~ ~ o ~, 1 N T ~ Q ~ :p ~°,~ ~ ~ ~ .~ ~ .~ ~ ~ ° o w ° E ~ ' >, ' >, ' >, T d~ ~ ° ~ c °' o (B N ~ p- E . ~ C ~ Q ~,' p- ~, O. ~~,, 1 E T C ~' ~ ~ ..~. ~ ,~~'', ~ ~ CB p ~ "~',, '~ a. E _T N
,'~ 13. ~' fl- C E C ~j C ~ C ~fj ~ U7 C N ~ ~ C C
CC i C6 O 'C N N N ~: N ~ ~ Q O .~..
U 1 l a. ~, Q. ~ Q ~ tZ r, x fl.
N ~ N ~ O ~ O O O p O O ~ O O ~ = c4 O N
C r- C ~ U ~ U p U p U Q s.. N U ~ T ' U
N O ~ N ~ ~, 1 7, N ~, N ~, N N O ~ ._. ~ ~, 1 m m U ~? U ca U ca U ca U ~°- ° U ~ uJ r- U ~?
U I~ N I~ N I~ .r_. 1~ .'.. f~ .'r 1~ ,.L. N ~ O 1~ N (V ~ I~
C~ C
N C.~O ~ N ~ N N O
U
N /~ N ~ N M ~ /~ N
N N N N
M ' I
I I Z 2 Z = O V ~ uJ

U

ii _ L _ _ _ _ O ~ ,~ ~ O ~ O O O
/ N '-' L
U N. ~ ~ a w a a. a.
c / c c ~ c L
M
Z Z I Z I I I I Z Z

Q
N N N N ~M c~ M M c'~~ M
Z
X
W

~I7 fG N N N cO c~ .~ CC ~ CB N
c ~ fB , 'C ~ ~ C
E O .Q C .p N N N "; ~ O
tn tn N ~ O
~T ~ ~ O E O ~ ~ ~ N
N Q ~ >, ~ ~, ~; O O ~ ~ ~ C Q C
Q c N N '~ u7 O_ O O
~ ,~ ~ Q~ ~ ~ ~ N -pp N N
Q C C ~ ~ ~ ~ E O C CE O
o ~ Q ~.c ~-c E o E o v c ~ a~ Qc c Q
fl. E >, '° ~t Q ~. a .i, m .>. 'r' E o ~ o o ~ ~ cu c .c Q ~c? ~ cv >, cu a. c a c ~= 'n ~ ~ Q .c >. ~n '- ~, ° r Wn c ~n ° .°_ ° -°_ Q c ' 'n c ~
N -° a a o Q ~ ay a E °-.E o :o a c ~t °. ~ o 0 0 0 0 0 ~ ~>, ~ ~~, n E o ~ ~ ~ °- o (6 N ~ N ~ U Q U O 'Q p- 'O d c ~j~ d ~ ~ 47 N
Z ~r 7,'c VN >,N.~.~~'~~'QC7,pr..~-..p.
... ..-. , p U CO ~ ~ _, ~ Q .c p (~ N O p N ~ i w-~. f~ .C-. N ~ N ~ 7, ~, cC ~ O N N
U Q N fl. r r ~ ~ , N N Q.
O fE O ~ ~ ~ ~ ~ C O N O N r C ~ ~ t6 O
U " U ~ m ~ ~ ~ p ~ O p Q ~ N r_ _ ~ U tn n t p t .~. , T
s U '~ U et c ~ m ~n a cNC m ~ r o d -°°
U 1~ N I~ N N ~ N ~ 1~ : I~ .-'. N ca N N I~ N I~ N
~ C
O ~ O
:.- ~ U ~ N ~ ~ p O N N N O O O O O
o M M
N ~ N M M Q N N N Q A ~ A D
>, j, ~ ~, >, Cfl O p ~ ~ O O ~ \ I \ I \ I
lY d ~ m ~ (i !Z W
C ~i C C C
i ~ o i i s s i i i Q Q Q Q Q Q Q Q ~ Q
O O O O O O O O O O
~ ~ ~ !i ~ !i ~ ~ d i i i ~ i i i i i i C O O O C C O C O C
i i ~ i i i i i i uJ uJ
L
O M
Z Z = Z = Z 2 Z Z
i _N
Q _ cDMM~d'~dN'~d~' Z
X
LJJ

1 , 1 ~ i 1 ' 1 1 ~p n 1 .~ p ~ ~ a y ~ ~ ~ am n 'w a>
' ui ~ ~, n W n ~ ci~ ~n ~r? c y ~ 1 : ~_ ~ ~ ~t et _ . ' o n E a o >, m o m o ~ ~ : ~
.

C 1 N Q. d N -p N
7 C CB c0 O fa L

O , Q ~ ~ N '0 E a ~
Q d N O ~ O
~

. _ ~ ~ ~ ~ O _ . ~ O p 7 ~
i p tC

v , ~ O
Ln d I '~ ~ ;C .~ L! O
~ a C I
~ ~ O C D
~ C

~ C ~ i n _ Q , ~, C 1 ~ Q. p ~ Q O ~ Q C
a C ~ C ;D , O ~ O ~ N ~, ~ E 1 OL
-a ~ ;p C 'p ~ ~

O d _ _ O, C ~ _ ~ ~ Q-~ ~, O - .p ~- 'C C ~E
~ ~ E

1 ~ V c ~. O C CO Wp O ' . ~_ N . 1 ~ . ~, L
C (~ L L Q
L

y, ~ 1 1 W 1 , ~ ~ 1 t6 O N ~p ' M M E ~"~
t= ~, 'C 7, ~ ~ 1 , ~ 1 1 ~ ~ a a 0 ~ n. ~, Q ca .L

Z - w ~ ~ ~ ~ ~ ~ co ~ cu m m p m Q. ca ,n ~, . . ~ C mn ~ ~ mn C mn cB ~ -a c ~ , V co N Q - ~ m Q fl . -- ~. ' Q ~ ~ o co ~
Q

r ~ O r O . O . 1 _ O ~ ~ O O _ N , O ~ O
O

O ~ O O
U U ~ U U C U
~ N ~

LL = p ~ p O ~
~ N

O ' .,., >, 7, ..Q >, ~, T O N

ca 111 U U U U U 00 U cc ~ ~~ cu ca :~

1 , I ' ~ 1 1 1 1 ' L
U .' ~ ~ L ~ N L 1 O N ..
N 1~ C N - I~ I~ 1~ N
,.. I~ .. O c6 .. tn N
'6 O

O ~ ' Q ' M O M
O

... O O O N O ~ N O O
O O O

U M M M M M

N ~ _ N r N /~ O

/~ /~ /~ I~ A
N

Q Q Q N N N

vU ~0 ~p ~ I Z I Z
, , , , O

O

7, 7, !? s2 Z Z ~ ~ ' ' , , , ' ' II II ' u7 ~ , ' , , s_ j, j, j, O O

!~ !~ !Z M >, O O O

a a ~ ' ' U uJ

s C

, , , N
Z ~ ~ Z = ~ ~ = Z

W

>, Q- M >, I Z 2 ~ Z 2 Z
' , , , p_ , , ' U FLU
~

, , c a~

a 0 M ~ M ~ ~ ~

' d t Z d ' 7 x W

' v c~'n v ~ up .E ~.c~
N N ~ N N O O N O
cC c0 ~ c6 c4 ~ ~ CC N a ~p N D N ~ ~ O ,O N ;Q N c6 N O
C ' C C C '~ ~' C ,O C p- E
~ ~ ~C7 CO O L~ tn - tn ~ ~ N ' ; N
G. C Q G .~ O .0 C -Q C O O ~_ N .~ C Q C ~ CE
Wn '~ :° .~ .° E o E o w :a o v c v a E °- E ~~, ~ n~'. E n E '_ ~ '~ ~ a E ~. E
C ~C G 'C w.. ~ 'C ~ .C ~, i ~, ~ ~ ~C ~ 'C
~, ~ >, c 'o N ~, ~ >, ..- c .- C V >, G >, ca o a ~ n. a~ ~ ~' Q. ~ n ~ :n ~ ~ ~ ~. ~. fl. >. o co c~ ao cu o ~L ~ c~ ~ c~ o. ~ a ~ ~ ; ca ~ cu >, >, ~, o 0 ~ v u~ T a -C u? ~ u? ~ '~, ~ '~, = u? C 'n ~ .;
Z ~-T. r r.T.. r V ~CC N r N r V Q U Q N ~ ~ r :~ VI
O C _O ' ' ~ _O ~ _O , , ~ O ~ _O i O N O ~ N ~ O ~ O ~' ~ ~ ~ ~ O ~ O ~i U_ d N Q N j,~ ~ N T N ' ~ ~ ~ T N v N
_O CO _O (6 ~ O N ~ N ~ ..~'. r_ ,-~'. r_ N ~ _, ~ N
U .L U .L m C L C L ~ O O O C L D L C
.~C U ~ U N c ~ m '~ m '~ m o m o m ~ ~ N pop r°~ a~
N ~ N ~ ~ c6 c U N N N N 'vt ~'. N N N ~ M c0 ~ c6 N N N a~ N '~ O
tn ~ C~ 00 f~
c V Wn ~ ~ ~ ~ ~ c~ c~
° r- r~ N N (h ~ ~ ~ ~ N
M M N
I ~ I ~ ~ Z = ~ ~ ~ ~ ~ I
i ~ i i i i i o ~ ~ i i o >, >, ~ Q Q
O O ~ >' >' >' L_ L_ ~ ~ O O
W LIJ ~ W
i i ~ i ~ , i i C C i C C
N
i i z ~ Z w M
U
Z
Q Q
o ~ = I I I I I I I
i ~ ~ ~ i ~ i ~ ~ i i ' C
i N
Q _ Z
X
W

, ~ = 'n ° , a~
a> ~ >, c ~ ° u~ c 'T ~ t!7 u7 Wp N N -p_ N ~ ,~ ~ O
Q 'O ~ ~ ~ E :p O .E O ~ O
_ .~ , ~ , O N
E o 'n..~ ~ ~ ~ a ~~ c ~, c_ '~ .-'_~a ~
a~ a~
>, p ~ y°- o o a '~ a ° y°- E o E ui s c ~t ~ E ~ E ~ a. ar> ~ E ° E '~ ~ ' ' ' ay_ .~ , ' ~ ~ 'T an M ~ a~ 'c w- 'c ~n >, ~ ° Q
~' E c~ ~~ ~~ N o E ~ ~a ~ ~ ~ ~ ~ crs X T ~ ~ ~ ~E p-~E >, N ~p cB I~ W N .~ ~t y st ._ N N ~ 'C I~ C .t.. C ~' r t r 7, C >, O- >, ~
E _O~ Q~ .-~'._fl- ~_O- ~ '~ ~p ~O ~~ ~~ ~O
V ~ ~,' ~ cv -c cC ~ ~ ~ O ~ O ~ ~ ~ N
' N ' N ' E E
U ~ Z ~ ,~, N ~ ~ ~ ~ N O ~p 0 ~
C ~7 M O
Q~ t N O .c N t N ~ N ~: N O N O O N N N N ~ ~ O O ca O
O ~ O O N ~C N C3 j, ~ ~ ~ ~ ~ ~ cNE 7, "; j~ ~
N 00 ~~ ° 00 '.~ 00 '~ U ~°- ° ~ 'n 00 ~ t1J 'L U ~' U 't U N N N ~ O N N N c~ I~ ~ O ~t ~ N ~ ~ v~ N N N N
N t~ ~1' lO M 1~ 0 0 0 N
UNNN('~~NN~(MtMN
Cfl N 0~0 N N
N N N M N N ~ M M N
i ~ ~ ~ ~'Z ~'Z ~ ~'Z
I
a N
O
a a a a a a a a a o a _ ~ _ uJ uJ uJ uJ W uJ W W
w L_ \ _ _ ~_ Z I Q L1J ~O ' a L1J
I ~ ~ a O M
a a a a a a ~ a a a Q
(~ Cfl CO C!J ~ I~ f~ f~ f~ I~
X
LIJ

yn v> yn ~ ~, ~ '~ , a~
.c c_ ~ et = ~ Q' ~ 'c o .°- ui o ,~ ~ ~, '° o E Q ~- o ~t ~ ~C ~ r N
T ~, O ~ O >, ~, ...1 p :p C N O ;~ ' cB
C fl. ~ ~ O C Q Y O ~ e- ,t.. ~ N ~ N
a~ c6 -o_ o yn s ~ v n°~ ~ ui ~ o °' N t ~ o o u'? E c >, c a. m , ~ >, ~ Q o E a~
v ~ .~. ° .~ ~ ~ ~. r ~ ',~ o :a_ ~ cNa v u~ ~ >, ~n ~. yn o , o >, ,n ~ ~ . , .~ ~ s c O t C ~, E N ~ Q r'., Q. E O ..~~. N O ~, N .Q
c ' O O 'c O
~_; N yp_ O >, ~, N L ~ ~ >, ,t... ~ >, N C ~ E E
N T c >, E = a .s c nwn ~ Q N ~
N C 'L a tB ~ "; ~ ~ ~ cU E ~ N ~ tf~ O
Q ~~ ~ ~ ~ N C ~_ ~~ ~ ~~ C U ~' CB
Q ~ ~ ~ - ~, N ~
uj v ~j N O C tn C ~ p p O N N C t E (' (li N ~ >, p N O E O, O ~ ~ p ~ .~ I ~ .n U t ~ N ~ ~ N Q ~ Q. ~ i ~ j, N ~ ~ C d O 7, ~ ~ O
O O ~ O N ~ O O O ~ ~ V c0 p O O E Q N
N ~, C N ~, ~ C ~ i U ~' c ~ N
N >, ~ ~ N ~, ~ >, ~ ~, ~ ;0 0 ~ 0 ~~ L ~7 ~, ~ N ,~~, C6 U ~ uJ m t~ '~' U ~ U L ~ r~ ~ ~ >. c U ~, U N ~ O ~ ~ ~ ~ I~ ~ O N w 'C N N d' ~ "O 1~ c ~. 00 E u7 ~ C
00 ~ ~ O ('~ N
V N ~ CV N N M N N
O O M N ONp ~ ~ O N M N
N N N N CO N
M
U U O
O O
i~ I~ I~
I~ I~ I
r° r°
M
. . . . . . . . .
>, sZ Q
W LlJ W LJJ n- ~ W UJ W
i i i ~ ~ 'O i i i N _ >, O 7.
Z Z = Z Z Z = ~ I
i i ~ i ~ i _N
O CO f~ 00 07 O ~ N ('~ d' (a Z r~ I~ f~ I' ao ao ao ao ao X
W

' 'n , o ~~.>, 'n c .
0 0 , 'c = c ~ c o Q ~ c u~ E
N T O ~' Q >, .~ .D O, ~ cC ,C .~ ~ j, >, c U N .~ ~ ~ E E '~ ,, u, ~, E
x :E r c° c ' o 'c ~~ C z E 'c m O ~ ~ L N ~ ~ T .O ' r .c fn G~ "'', O- r ~ O- N ._ N p X Q. 'ch ~ _r C ~ T O ~ ~ ~ j, ~_-' ~ -Lp 'n N _O
O ' N _ O ~ _ U O L Q >, ~, O
NO X~i' 1~~ NO ~N d'N NO
' N N _O O N = ~ ~ O ~ tt7 _>, ' ~ O
._C ~_ p ~' cNC p N N L tNC
O E tI7 O ~ ~ N ~ N ".' N ~ Q. ~ O ."' >' O
E ~ . , N E ~ ~ ~ ' ~ ' O O ~ ' fn ~, n-. c ~ . ~ c >, ~ ~,' ' ~' N U O ~1,' ~
,~ .C ~ ~ ~' .O XO p ~ N ~ C U cNE _~ ~ C st c ~ E N~ E >,~ ~ c~ ~ ch t~.°- c c"' ~ r°.~
_U_ n E ~i. ' °' ~. c :-° o n. ~ ~ ~ ~ E o Q ~ ~ c~ a~
O ~, O- N ~ t~ U E ~f7 O O ~.~'. ~ N ~ ~ ~tj _O O E -~
E V~~ cT~ m'T '= U~ 7~ c~C UcNC ~~t17 ~,- ~ ~ ~ ~ d_' T T;a_ m ~ ~ ~' ~',a_ Q i~ ' ~, :O_ N ~, ~_ O ~ C
U ~c~ oon" c5 iE ~~o~n°i ooEEr~~o~N=o ~ _c ~O O ('~~
cV N N M c'~
M N ~ ~ O O C~~
N N N c'~ ('~
LL LL ~ LL
p 0 ~ w I w ~ ~ ~ w i i I I
O
J
~, ~ ~, ~, a w w w w w w w w Q ~ ~ ~ '~' x w o ~ o ~ >, >. ~ . m o- '~ ~ ~ L °- ~ C
o ~ o ~ °- >, c o ~ ~ ~ ~. ca r ~ ~ ~ °~ ~ a~ E
C N C N ~ ~ ~ ~ V ~ ~,~C E _ ~ ~C
CB c0 ~L v .C >' r; ct ~~ ~ N C a N p X Q
X
i ;' ~ "; O 0 - ~, ~ c~ O t0 T O O fC
~ O t _Q' N """' O ~t7 w N ~ tn 7, ~ ~, ~ O N ~ ~ C N U N ~ O
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ca The structures of the examples of compounds (la) to (Id) synthesised hereinbefore were confirmed by NMR-spectroscopy.
s NMR-spectroscopic data of selected compounds:
Example (3) 1 H-NMR (DMSO-d6): 8 = 14.10 (1 H, s, broad, NH); 8.24 (1 H, s, H2); 7.35-7.14 (5H, m, Aryl-H); 4.12 (2H, t, J = 7.5 Hz; N-CH2CH2CH3); 4.09 (2H, s, -CH2-Phenyl);
1.73 o (2H, m, N-CH2CH2CH3); 0.89 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (4) 1 H-NMR (DMSO-d6): 8 = 13.28 (1 H, s, broad, NH); 8.24 (1 H, s, H2); 7.35-7.14 (5H, m, Aryl-H); 4.15 (2H, t, J = 7.5 Hz, N-CH2CH2CH2CH3); 1.68 (2H, m, N-CH2CH2CH2CH3); 1.32 (2H, m, N-CH2CH2CH2CH3); 0.90 (3H, t, J = 7.5 Hz, N-CH2CH2CH2CH3).
Example (5) 1 H-NMR (DMSO-d6): b = 13.22 (1 H, s, broad, NH); 8.25 (1 H, s, H2); 7.35-7.14 (5H, 2o m, Aryl-H);5.33 (1 H, m, CH-Isopropyl); 4.09 (2H, s, -CH2-Phenyl);
1.55 (6H, d, J = 7.0 Hz, (CH3)2-Isopropyl).
Example (6) 1 H-NMR (DMSO-d6): 8 = 13.66 (1 H, s, broad, NH); 7.34-7.14 (5H, m, Aryl-H);
25 4.11 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 4.07 (2H, s, -CH2-Phenyl);
2.79 (2H, qu, J = 7.5 Hz, -CH2CH3); 1.71 (2H, m, N-CH2CH2CH3);
1.29 (3H, t, J = 7.5 Hz, -CH2-CH3); 0.90 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (7) 30 1 H-NMR (DMSO-d6): 8 = 13.70 (1 H, s, broad, NH); 7.43-7.14 (5H, m, Aryl-H);
4.09 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 4.07 (2H, s, -CH2-Phenyl);
2.75 (2H, t, J = 7.5 Hz, -CH2CH2CH3); 1.74 (4H, m, N-CH2CH2CH3; -CH2CH2CH3); 0.92 (6H, m, N-CH2CH2CH3; -CH2CH2CH3).
35 Example (8) 1 H-NMR (DMSO-d6): 8 = 7.34-7.12 (5H, m, Aryl-H); 4.07 (2H, s, CH2-Phenyl);
3.55 (3H, s, N-CH3); 3.23 (1 H, m, CH-Cyclopentyl); 2.14-1.52 (8H, m, CH2-Cyclopentyl).

Example (9) 1 H-NMR (DMSO-d6): 8 = 13.68 (1 H, s, broad, NH); 7.40-7.14 (5H, m, Aryl-H);
4.19 (2H, qu, J = 7.5 Hz, N-CH2CH3); 4.09 (2H, s, CH2-Aryl); 3.24 (1 H, m, CH-Cyclopentyl); 2.26-1.50 (8H, m, CH2-Cyclopentyl); 1.26 (3H, t, J = 7.5 Hz, N-CH2CH3).
Example (10) 1 H-NMR (DMSO-d6): b = 13.65 (1 H, s, broad, NH); 7.38-7.14 (5H, m, Aryl-H);
4.11 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 4.08 (2H, s, Phenyl-CH2-); 3.23 (1 H, m, CH-Cyclopentyl); 2.14-1.49 (10 H, m, CH2-Cyclopentyl; N-CH2CH2CH3); 0.89 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (11 ) 1 H-NMR (DMSO-d6): 8 = 13.85 (1 H, s, broad, NH); 7.62-7.33 (5H, m, Aryl-H);
~5 4.34 (2H, t, J = 7.5 Hz, N-CH2); 4.28 (2H, s, CH2-Phenyl); 3.43 (1 H, m, CH-Cyclopentyl); 2.33-1.38 (12H, m, CH2-Cyclopentyl; N-CH2-CH_2CH_2-CH3);
1.10 (3H, t, J = 7.5 Hz, N-(CH2)3-CH3).
Example (12) , 20 1 H-NMR (DMSO-d6): 8 = 12.58 (1 H, s, broad, NH); 7.52-7.14 (10 H, m, Aryl-H);
5.52 (2H, s, N-CH2-Aryl); 4.18 (2H, s, -CH2-Aryl); 3.31 (1 H, m, CH-Cyclopentyl);
2.21-1.50 (8H, m, CH2-Cyclopentyl).
Example (13) 25 1 H-NMR (DMSO-d6): 8 = 12.38 (1 H, s, broad, NH); 7.34-7.14 (5H, m, Aryl-H);
4.08 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 4.6 (2H, s, -CH2-Phenyl); 3.69; 3.59 (8H, m, morpholin-H); 1.70 (2H, m, N-CH2CH2CH3); 0.88 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
3o Example (14) 1 H-NMR (DMSO-d6): ~ = 12.26 (1 H, s, broad, NH); 7.38-7.14 (10 H, m, Aryl-H);
4.08 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 4.06 (2H, s, CH2-Phenyl); 3.57; 2.46 (8H, m, -CH2-Piperaz.); 3.52 (2H, s, N-CH2-Phenyl); 1.70 (2H, m, N-CH2CH2CH3);
0.88 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).

Example (15) 1 H-NMR (.DMSO-d6): 8 = 7.40-7.14 (5H, m, Aryl-H); 4.76 (3H, s, broad, NH, NH2);
4.08 (2H, t, J = 7.5 Hz; N-CH2CH2-CH3); 4.06 (2H, s, -CH2-Phenyl); 3.48; 2.79 (8H, 2m, CH2-Piper.); 1.90 (3H, s, CH3COOH); 1.70 (2H, m, N-CH2CH2-CH3); 0.88 (3H, t, J = 7.5 Hz, N-CH2CH2-CH3).
Example (16) 1 H-NMR (DMSO-d6): b = 13.82 (1 H, s, broad, NH); 7.34-7.14 (5H, m, Aryl-H);
4.19 (2H, qu, J = 7.0 Hz, N-CH2CH3); 4.08 (2H, s, -CH2-Phenyl); 3.93; 3.43 (4H, 2m, ~0 2 CH2-0); 3.09 (1 H, m, -CH-THP); 2.00-1.68 (4H, m, 2-CH2-THP); 1.25 (3H, t, J =
7.0 Hz, N-CH2CH3).
Example (17) 1 H-NMR (DMSO-d6): b = 13.84 (1 H, s, broad, NH); 7.34-7.14 (5H, m, Aryl-H);
4.18 (2H, qu, J = 7.0 Hz, N-CH2CH3); 4.08 (2H, s, -CH2-Phenyl); 4.08-3.74 (4H, m, 2 CH2-O-3THF); 3.62 (1 H, m, CH- 3 THF); 2.29 (2H, m, CH2- 3 THF); 1.25 (3H, t, J =
7.0 Hz, N CH2CH3).
Example (18) 1 H-NMR (DMSO-d6): 8 = 13.64; 12.76 (2H, 2s, broad, 2NH); 7.35-7.14 (5H, m, Aryl-H); 4.02 (2H, s, -CH2-Phenyl); 3.23 (1 H, m, CH-Cyclopentyl); 2.14-1.50 (8H, m, CH2-Cyclopentyl).
Example (19) 1 H-NMR (DMSO-d6): b = 13.42; 13.20 (2H, 2s, broad, 2 NH); 8.24 (1 H, s, H2);
3.20 (1 H, m, CH-Cyclopentyl); 2.17-1.50 (1 H, m, CH2-Cyclopentyl).
Example (20) 1 H-NMR (DMSO-d6): 8 = 13.86 (1 H, s, broad, NH); 8.22 (1 H, s, H2); 3.58 (3H, s, N-3o CH3); 3.23 (1 H, m, CH-Cyclopentyl); 2.14-1.52 (8H, m, CH2-cylcopentyl).
Example (21 ) 1 H-NMR (DMSO-d6): b = 14.04 (1 H, s, broad, NH); 8.24 (1 H, s, H2); 4.13 (2H, t, J =
7.5 Hz, N-CH2CH2CH3); 3.21 (1 H, m, CH-Cyclopentyl); 2.14-1.52 (10 H, m, CH2-Cyclopentyl; N-CH2CH2CH3); 0.90 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).

Example (22) 1 H-NMR (DMSO-d6): 8 = 13.68 (1 H, s, broad, NH); 4.12 (2H, t, J = 7.5 Hz, N-CH2CH3);3.20 (1 H, m, CH-Cyclopropyl); 2.45 (3H, s, -CH3); 2.12-1.52 (10 H, m, CH2-Cyclopentyl); 0.89 (3H, t, J = 7.5 Hz, N-CH2-CH2CH3).
Example (23) 1 H-NMR (DMSO-d6): b = 13.64 (1 H, s, broad, NH); 4.12 (2H, t, J = 7.5 Hz, N-CH2CH3);3.20 (1 H, m, CH-Cyclopentyl); 2.80 (2H, qu, J = 7.5 Hz, -CH2-CH3);
2.13-1.52 (10 H, m, CH2-Cyclopentyl; N-CH2-CH2CH3); 1.29 (3H, t, J = 7.5 Hz, -1o CH2-CH3); 0.90 (3H, t, J = 7.5 Hz, -N-CH2-CH2CH3).
Example (24) 1 H-NMR (DMSO-d6): 8 = 13.88 (1 H, s, broad, NH); 7.35-7.14 (5H, m, Aryl-H);
4.13 (2H, s, -CH2-Phenyl); 4.11 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.19 (1 H, m, CH-Cyclopentyl); 2.09-1.52 (1=H, m, CH2-Cyclopentyl; N-CFi~2CH2CHg);
0.89 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (25) 1 H-NMR (DMSO-d6): 8 = 13.60 (1 H, s, broad, NH); 7.43-7.14 (5H, m, Aryl-H);
4.36 (2H, t, J = 7.5 Hz, N-CH2(CH2)3-CH3); 4.19 (2H, s, -CH2-Phenyl); 3.40 (1 H, m, CH-Cyclopentyl); 2.31-1.24 (14H, m, CH2-Cyclopentyl; N-CH2(CH2)3-CH3);
0.89 (3H, m, N-(CH2)4-CH3).
Example (26) 1 H-NMR (DMSO-d6): b = 13.85 (1 H, s, broad, NH); 8.16 (1 H, s, H6); 7.35-7.14 (5H, m, Aryl-H); 4.15 (2H, s, -CH2-Phenyl); 3.59 (3H, s, N-CH3).
Example (27) 1 H-NMR (DMSO-d6): S = 14.02 (1 H, s, broad, NH); 8.19 (1 H, s, H6); 7.35-7.14 (5H, 3o m, Aryl-H); 4.18 (2H, s, -CH2-Phenyl); 4.15 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 1.75 (2H, m, N-CH2CH2CH3); 0.93 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (28) 1 H-NMR (DMSO-d6): b = 13.50, 12.92 (2H, 2s, broad, 2NH); 8.10 (1 H, s, H6);
s5 3.24 (1 H, m, CH-Cyclopentyl); 2.17-1.52 (8H, m, CH2-Cyclopentyl).
Example (29) 1 H-NMR (DMSO-d6): 8 = 13.70 (1 H, s, broad, NH); 8.18 (1 H, s, H6); 3.59 (3H, s, C-CH3); 3.25 (1 H, m, CH-Cyclopentyl); 2.15-1.52 (8H, m, CH2-Cyclopentyl).

Example (30) 1 H-NMR (DMSO-d6): 8 = 13.70 (1 H, s, broad, NH); 8.20 (1 H, s, H6); 4.25 (2H, qu, J
= 7.0 Hz, N-CH2-CH3); 3.27 (1 H, m, CH-Cyclopentyl); 2.21-1.52 (8H, m, CH2-Cyclopentyl); 1.29 (3H, t, J = 7.0 Hz, N-CH2-CH3).
Example (31 ) 1 H-NMR (DMSO-d6): 8 = 13.74 (1 H, s, broad, NH); 8.18 (1 H, s, H6); 4.14 (2H, t, J =
7.5 Hz, N-CH2-CH2CH3); 3.25 (1 H, m, CH-Cyclopentyl); 2.15-1.54 (10 H, m, CH2-Cyclopentyl; N-CH2-CH2CH3); 0.90 (3H, t, J = 7.5 Hz, N-CH2-CH2CH3).
Example (33) 1 H-NMR (DMSO-d6): 8 = 13.62 (1 H, s, broad, NH); 4.11 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.23 (1 H, m, CH-Cyclopentyl); 2.37 (3H, s, -CH3); 2.14-1.50 (10 H, m, CH2-Cyciopentyl, N-CH2CH2CH3); 0.90 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (34) 1 H-NMR (DMSO-d6): b = 8.22 (1 H, s, Hz); 4.13 (2H, t, J = 7.5 Hz, N-CH2CH2CH3);
2.75 (2H, qu, J = 7.5 Hz, -CH2CH3); 1.74 (2H, m, N-CH2CH2CH3); 1.29 (3H, t, J
=
20 7.5 Hz, CH2-CH3); 0.92 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (35) 1 H-NMR (DMSO-d6): 8 = 13.62 (1 H, s, broad, NH); 4.12 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.25 (1 H, m, CH-Cyclopentyl); 2.74 (2H, qu, J = 7.5 Hz, -CH2CH3);
25 2.17-1.51 (10 H, m, CH2-Cyclopentyl; N-CH2CH2CH3); 1.29 (3H, t, J = 7.5 Hz, -CH2CH3); 0.90 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (36) 1 H-NMR (DMSO-d6): b = 13.58 (1 H, s, broad, NH); 4.12 (2H, t, J = 7.5 Hz, N-3o CH2CH2CH3); 3.24 (1 H, m, CH-Cyclopentyl);2.69 (2H, t, J = 7.5 Hz, -CH2CH2CH3);
2.15-1.50 (12H, m, CH2-Cyclopentyl; (CH2CH2CH3)2); 0.95; 0.90 (6H, 2t, J = 7.5 Hz, (CH2CH2CH3)2)-Example (37) 35 1 H-NMR (DMSO-d6): 8 = 13.62 (1 H, s, broad, NH); 4.13 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.24 (1 H, m, CH-Cyclopentyl); 3.05 (1 H, m, CH-Isoprop.);
2.14-1.50 (10 H, m, CH2-Cyclopentyl; N-CH2CH2CH3); 1.32 (6H, d, J = 7_5 Hz, CH3-Isoprop.); 0.90 (3H, t, J = 7.5 Hz, CH2CH2CH3).

Example (38) 1 H-NMR (DMSO-d6): b = 13.62 (1 H, s, broad, NH); 4.12 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.24 (1 H, m, Cyclopentyl-H); 2.70 (2H, t, J = 7.5 Hz, CH2-CH2CH2CH3); 2.15-1.26 (14H, m, CH2-Cyclopentyl; N-CH2CH2-CH3, CH2-CH2CH2CHg); 0.90 (6H, m, N-CH2CH2CH3); (-CH2)3-CH3).
Example (39) 1 H-NMR (CDC13): b = 4.36 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.40 (1 H, m, CH
-Cyclopentyl); 2.32-1.63 (10 H, m, CH2-Cyclopentyl; N-CH2CH2CH3); 1.46 (9H, s, 1o C(CH3)3; 1.02 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (40) 1 H-NMR (DMSO-d6): 8 = 14.28 (1 H, s, broad, NH); 8.26-7.45 (5H, m, Aryl-H);
4.14 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 2.71 (2H, t, J = 7.5 Hz, -CH2CH2CH3);
~5 1.76 (4H, m, (-CH2CH2CH3)2); 0.98; 0.93 (6H, 2t, (-CH2CH2CH3)2).
Example (41 ) 1 H-NMR (DMSO-d6): 8 = 7.44-7.05 (4H, m, Aryl-H); 4.13 (2H, s, CH2-Phenyl);
4.11 (2H, t, J = 7.5 Hz, N-CH2CH2-CH3); 2.68 (2H, t, J = 7.5 Hz, -CH2CH2-CH3);
20 1.74 (4H, m, (-CH2CH2-CH3)2); 0.95; 0.89 (6H, 2t, J = 7.5 Hz, (CH2CH2-CH3)2).
Example (42) 1 H-NMR (DMSO-d6): 8 = 13.64 (1 H, s, broad, NH); 4.12 (2H, t, J = 7.5 Hz; N-CH2CH2CH3); 2.76 (4H, m, (CH2CH3)2); 1.73 (2H, m, N-CH2CH2CH3));
25 2.29 (6H, m, (CH2-CH3)2); 0.90 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (43) 1 H-NMR (DMSO-d6): 8 = 14.19 (1 H, s, broad, NH); 8.31 (1 H, s, H2);
8.16-7.38 (5H, m, Aryl-H); 4.21 (2H, t, J = 7.5 Hz, N-CH2CH2CH3);
30 1.83 (2H, m, N-CH2CH2CH3); 0.98 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (44) 1 H-NMR (DMSO-d6): 8 = 13.78 (1 H, s, broad, NH); 8.19-7.43 (5H, m, Aryl-H);
4.21 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 2.83 (2H, qu, J = 7.5 Hz, -CH2CH3);
35 1.81 (2H, m, N-CH2CH2CH3); 1.33 (3H, t, j = 7.5 Hz, -CH2CH3);
0.95 (3H, t, J = 7.5 Hz, -N-CH2CH2CH3).

Example (45) 1 H-NMR (DMSO-d6): 8 = 13.70 (1 H, s, broad, NH); 8.19-7.38 (5H, m, Aryl-H);
4.21 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.28 (1 H, m, CH-Cyclopentyl);
2.19-1.50 (10 H, m, CH2-Cyclopentyl; N-CH2CH2CH3); 0.94 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (46) 1 H-NMR (DMSO-d6): 8 = 8.26 (1 H, s, Hz); 7.84; 7.10; 6.69 (3H, 3m, Furyl-H);
4.10 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 1.81 (2H, m, N-CH2CH2CH3);
0 0.98 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (47) 1 H-NMR (DMSO-d6): 8 = 13.56 (1 H, s, broad, NH); 7.70; 6.91; 6.50 (3H, 3m, Furyl-H); 4.00 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 2.66 (2H, qu, J = 7.5 Hz, -CH2CH3);
1.61 (2H, m, N-CH2-CH2-CH3); 1.14 (3H, t, J = 7.5 Hz, N-CH2CH2CH3);
0.77 (3H, t, J = 7.5 Hz, -CH2CH3).
Example (48) 1 H-NMR (DMSO-d6): b = 13.84 (1 H, s, broad, NH); 8.00; 7.18; 6.78 (3H, 3m, Furan-2o H); 4.26 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.37 (1 H, m, CH-Cyclopentyl);
2.28-1.62 (10 H, m, CH2-Cyclopentyl; N-CH2CH2CH3);
1.04 (3H, t, J = 7.5 Hz; N-CH2CH2CH3).
Example (49) 1 H-NMR (DMSO-d6): 8 = 12.84 (1 H, s, broad, NH); 8.26 (1 H, s, H2);
4.32 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.18 (1 H, m, CH-Cyclopentyl);
2.09-1.52 (10 H,m, CH2-Cyclopentyl; N-CH2CH2CH3);
0.83 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
3o Example (50) 1 H-NMR (DMSO-d6): 8 = 8.28 (1 H, s, H6); 8.15 (1 H, s, H2);
13.35 (2H, s, broad).
Example (51 ) 1 H-NMR (DMSO-d6): 8 = 13.74 (1 H, s, broad, NH); 8.34 (1 H, s, H6);
4.63 (2H, qu, J = 7.5 Hz, N-CH2CH3); 3.33 (1 H, m, CH-Cyclopentyl);
2.24-1.57 (8H, m, CH2-Cyclopentyl); 1.47 (3H, t, J = 7.5 Hz, N-CH2CH3).

Example (52) 1 H-NMR (DMSO-d6): b = 13.72 (1 H, s, broad, NH); 8.34 (1 H, s, H6);
4.53 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.34 (1 H, m, CH-Cyclopentyl);
2.20-1.57 (8H, m, CH2-Cyclopentyl); 1.87 (2H, m, N-CH2CH2CH3);
1.06 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (53) 1 H-NMR (DMSO-d6): 8 = 8.19 (1 H, s, H6); 4.00 (3H, s, N-CH3);
3.58 (3H, s, N-CH3); 3.42 (1 H, m, CH-Cyclopentyl); 2.18-1.57 (8H, m, CH2-o Cyclopentyl).
Example (55) 1 H-NMR (DMSO-d6): b = 14.12 (1 H, s, broad, NH); 8.44 (1 H, s, Hz);
4.53 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.28 (1 H, m, CH-Cyclopentyl);
5 2.17-1.55 (8H, m, CH2-Cyclopentyl); 1.87 (2H, m, N-CH2CH2CH3);
1.05 (3H, t, J = 7.5 Hz, N-CH2CH2CH3).
Example (56) 1 H-NMR (DMSO-d6): 8 = 8.28 (1 H, s, H2); 4.36 (2H, t, J = 7.5 Hz, N-CH2CH2CH3);
20 4.12 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.21 (1 H, m, CH-Cyclopentyl).
2.12-1.57 (12H, m, CH2-Cyclopentyl; (N-CH2CH2CH3)2);
0.92; 0.87 (6H, 2t, J = 7.5 Hz, (N-CH2CH2CH3)2)-Example (57) 25 1 H-NMR (DMSO-d6): 8 = 8.02 (1 H, s, H2); 4.45 (2H, t, J = 7.5 Hz, N-CH2CH2CH3);
4.14 (2H, t, J = 7.5 Hz, N-CH2CH2CH3); 3.24 (1 H, m, CH-Cyclopentyl);
2.14-1.57 (12H, m, CH2-Cyclopentyl; (N-CH2CH2CH3)2;
0.93; 0.89 (6H, 2t, J = 7.5 Hz, (N-CH2CH2CH3)2;

The following Table contains K;A~ (human) and K;A2 (rat) receptor binding values.
Table 20:
Example KiA1 KiA2 No.: nM nM

7 8,1 158 8 1, 9 363 9 1, 4 422 1,7 730 11 8, 3 345 13 5,2 82 25 10,3 1231 30 81, 5 3292 36 5, 8 731 37 6,4 307 38 6,4 532 39 6, 0 539 48 11, 4 4455 The following Table contains K;A~ (human) receptor binding values.
Table 21:
Example KiA3 No. nM

3 4,7 4 2,3 19 3,8 78 5, 3 The compounds of general formula (I) may be used on their own or combined with other active substances according to the invention, possibly also together with other pharmacologically active substances. Suitable preparations include, for example, tablets, capsules, suppositories, solutions, syrups, emulsions or dispersible powders.
Corresponding tablets may be obtained, for example, by mixing the active substance or substances with known excipients such as inert diluents, e.g. calcium carbonate, calcium phosphate or lactose, disintegrants such as corn starch or alginic acid, binders such as starch or gelatine, lubricants such as magnesium stearate or talc, ~o and/or agents for achieving delayed release such as carboxymethyl cellulose, cellulose acetate phthalate or polyvinyl acetate. The tablets may also be made up of several layers.
Coated tablets may be prepared analogously by coating cores produced in the same ~5 way as the tablets with agents conventionally used in tablet coatings, e.g.
collidone or shellack, gum arabic, talc, titanium dioxide or sugar. To achieve delayed release or prevent incompatibilities, the core may also be made up of several layers.
Similarly, the tablet coating may be made up of several layers to achieve delayed release, in which case the excipients used for the tablets may be used.
Syrups of the active substances according to the invention or combinations of active substances may additionally contain a sweetener such as saccharin, cyclamate, glycerol or sugar and a flavouring improving agent, e.g. a flavouring such as vanillin or orange extract. They may also contain suspension adjuvants or thickeners such as sodium carboxymethylcellulose, wetting agents, e.g. condensation products of fatty alcohols with ethylene oxide, or preservatives such as p-hydroxybenzoates.
Injectable solutions are produced in the usual way, e.g. by adding preservatives such as p-hydroxybenzoates or stabilisers such as alkali metal salts of ethylenediamine tetraacetic acid and are transferred into injection vials or ampoules.
The capsules containing one or more active substances or combinations of active substances may be produced by mixing the active substances with inert carriers such as lactose or sorbitol and packing them into gelatine capsules.
Suitable suppositories may be prepared, for example, by mixing with carriers intended for this purpose such as neutral fats or polyethyleneglycol or derivatives thereof.

A therapeutically active daily dose is between 1 and 800 mg, preferably 10 to 300 mg per adult.
The Examples which follow illustrate the invention without restricting its scope:
Examples of pharmaceutical formulations A) Tablets per Tablet ~o Active substance 100 mg Lactose 140 mg Corn starch 240 mg Polyvinylpyrrolidone 15 mg Magnesium stearate 5 ma 500 mg The finely ground active substance, lactose and some of the corn starch are mixed together. The mixture is screened, and then moistened with a solution of 2o polyvinylpyrrolidone in water, kneaded, moist-granulated and dried. The granules, the remaining corn starch and the magnesium stearate are screened and mixed together. The mixture is compressed into tablets of suitable shape and size.
B) Tablets per Tablet Active substance 80 mg Corn starch 190 mg Lactose 55 mg Microcrystalline cellulose 35 mg 3o Polyvinylpyrrolidone 15 mg Sodium carboxymethyl starch 23 mg Magnesium stearate 2 ma 400 mg The finely ground active substance, some of the corn starch, lactose, microcrystalline cellulose and polyvinylpyrrolidone are mixed together, the mixture is screened and processed with the remaining corn starch and water to form a granulated material which is dried and screened. The sodium carboxymethyl starch and the magnesium stearate are added to this, then mixed together and the mixture is compressed to form tablets of suitable size.
C) Coated tablets loer coated tablet Active substance 5 mg Corn starch 41.5 mg Lactose 30 mg o Polyvinylpyrrolidone 3 mg Magnesium stearate 0.5 mg 80 mg The active substance, corn starch, lactose and polyvinylpyrrolidone are thoroughly ~s mixed and moistened with water. The moist mass is pressect through a 1 mm mesh screen, dried at about 45°C and the granules are then passed through the same screen again. After the addition of magnesium stearate, curved tablet cores measuring 6 mm in diameter are pressed out in a tablet making machine. The tablet cores thus produced are coated in known manner with a covering consisting 2o essentially of sugar and talc. The finished coated tablets are polished with wax.
D) Capsules per capsule Active substance 50 mg 25 Corn starch 268.5 mg Magnesium stearate 1.5 ma 320 mg The substance and corn starch are mixed together and moistened with water. The so moist mass is screened and dried. The dry granules are screened and mixed with magnesium stearate. The finished mixture is packed into size 1 hard gelatine capsules.

E) Ampoule solution Active substance 50 mg Sodium chloride 50 mg Water for injections 5 ml The active substance is dissolved at its own pH or optionally at pH 5.5 to 6.5 in water and sodium chloride is added to render the solution isotonic. The resulting solution is filtered free from pyrogens and the filtrate is transferred under aseptic conditions into o ampoules which are subsequently sterilised and sealed by fusion. The ampoules contain 5 mg, 25 mg and 50 mg of active substance.
F) Suppositories Active substance - 50 mg Solid fat 1650 ma 1700 mg The hard fat is melted. At 40°C the ground active substance is homogeneously 2o dispersed therein. It is cooled to 38°C and poured into slightly chilled suppository moulds.
G) Oral Suspension Active substance 50 mg Hydroxyethylcellulose 50 mg Sorbic acid 5 mg (70%) Sorbitol 600 mg Glycerol 200 mg 3o Flavouring 15 mg Water ad 5 ml Distilled water is heated to 70°C. Hydroxyethylcellulose is dissolved therein with stirring. After the addition of sorbitol solution and glycerol the mixture is cooled to ambient temperature. At ambient temperature the sorbic acid, flavouring and substance are added. To eliminate air from the suspension it is evacuated with stirring.

Claims (31)

1. A compound of any one of general formulae (Ia) to (Id) wherein R1 or R3 denotes hydrogen, C1-4-alkyl or benzyl;

R2 denotes hydrogen, or C1-8-alkyl; phenyl which is optionally substituted by any of halogen, C1-4-alkyl, C1-4-alkyloxy, hydroxy and NR8R9; phenyl-C1-6-alkyl, phenyl-C2-6-alkenyl or phenyl-C2-6-alkynyl, wherein the phenyl ring is optionally substituted by any of halogen, C1-4-alkyl, C1-4-alkyloxy, hydroxy and NR8R9; an amine of formula NR8R9; a 5- or 6-membered heterocyclic group which is optionally C- or N-linked either directly or via a C1-4-alkylene bridge, containing one or more heteroatoms selected from the group comprising nitrogen and oxygen and optionally substituted by benzyl or C1-4-alkyl; a C3-6-cycloalkyl which is optionally substituted by any of =O, hydroxy, C1-4-alkyl and C1-4-alkyloxy; or any one of norbornane, norbornene, adamantane and noradamantane, optionally substituted by C1-4-alkyl;

R4 or R5 denotes, C1-8-alkyl, phenyl-C1-4-alkyl, phenyl-C2-6-alkenyl or phenyl-C2-6-alkynyl, wherein the phenyl ring is optionally substituted by any of halogen, hydroxy, C1-4-alkyl, C1-4-alkyloxy and NR8R9;

R6 denotes hydrogen, or C1-8-alkyl, wherein the alkyl is optionally substituted by any of halogen, hydroxy, =O, C1-4-alkyloxy, NR8R9, phenyloxy, -O-phenyl-C1-4-alkyloxy, benzyloxy, -O-benzyl-O-C1-4-alkyloxy, -OCO-C1-4-alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C1-4-alkylene, -CO-C1-4-alkyl, -CHO, =NOH, -COOH, -COO-C1-4-alkyl, -COO-phenyl, -COO-benzyl, -CONR8R9, -NHCO-C1-4-alkyl, -NHCO-phenyl, -CO-C1-4-alkyl-NR8R9, -SO2OH, -SO2-C1-4-alkyl or -SO2-phenyl; phenyl which is optionally substituted by any of halogen, hydroxy, C1-4-alkyl, C1-4-alkyloxy, benzyloxy, phenyloxy, -NR8R9, -OCO-C1-4-alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C2-4-alkylene, -CO-C1-4-alkyl, -C1-4-alkyl-NH2, -C1-4-alkyl-OH, -C1-4-alkyl=NOH, -COOH, -COO-C1-4-alkyl, -COO-phenyl, -COO-benzyl, -CONR8R9, -CO-C1-4-alkyl-NH2, -SO2OH, -SO2-C1-4-alkyl and -SO2-phenyl; phenyl-C1-4-alkyl, phenyl-C2-6-alkenyl or phenyl-C2-6-alkynyl, wherein the phenyl ring is optionally substituted by any of halogen, hydroxy, C1-4-alkyl, C1-4-alkoxy, benzyloxy, phenyloxy, -NR8R9, -OCO-C1-4-alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C2-4-alkylene, -CO-C1-4-alkyl, -C1-4-alkyl-NR8R9, -C1-4-alkyl-OH, -C1-4-alkyl=NOH, -COOH, -COO-C1-4-alkyl, -COO-phenyl, -COO-benzyl, -CONR8R9, -CO-C1-4-alkyl-NH2, -SO2OH, -SO2-C1-4-alkyl and -SO2-phenyl; a 5- or 6-membered heterocyclic group optionally C- or N- linked either directly or via a C1-4-alkylene bridge, which contains one, two or three heteroatoms selected from nitrogen and oxygen and is optionally mono- or polysubstituted by benzyl or C1-4-alkyl; a C3-6-cycloalkyl or C3-6-cycloalkyl-C1-4-alkyl group which is optionally substituted by any of =O, hydroxy, C1-4-alkyl and C1-4-alkyloxy; any one of norbornyl, norbornenyl, adamantyl and noradamantyl optionally substituted by C1-4-alkyl; any one of -CHO, -COON, -COO-C1-4-alkyl, -COO-phenyl, -COO-benzyl and -CONR8R9; or an amine of general formula NR8R9;

R8 denotes hydrogen, or a branched or unbranched C1-4-alkyl group; or a C-linked 5- or 6-membered heterocyclic group which contains one, two or three heteroatoms selected from the group comprising nitrogen, oxygen and sulphur and is optionally substituted by any of benzyl, C1-4-alkyl, C1-4-alkyloxy, halogen, -CN, -NO2, -NH2, -OH and =O; and R9 denotes hydrogen, or a branched or unbranched C1-4-alkyl group; or a C-linked 5- or 6-membered heterocyclic group which contains one, two or three heteroatoms selected from the group comprising nitrogen, oxygen or sulphur and is optionally substituted by any of benzyl, C1-4-alkyl, C1-4-alkyloxy, halogen, -CN, -NO2, -NH2, -OH and =O; or R8 and R9 together with the nitrogen atom in NR8R9 form a saturated or unsaturated 5- or 6-membered ring optionally substituted by a branched or unbranched C1-4-alkyl group, or by a - (CH2) 1-4-phenyl group;

or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.

2. The compound according to claim 1, wherein R8 and R9, together with the nitrogen atom in NR8R9, form a saturated or unsaturated 5- or 6-membered ring comprising one or more additional heteroatoms selected from oxygen and nitrogen.

3. The compound according to claim 1 or 2, wherein R2 is C1-6-alkyl.

4. The compound according to claim 1 or 2, wherein R2 is phenyl-C1-6-alkyl, phenyl-C2-6-alkenyl or phenyl-C2-6-alkynyl, substituted by fluorine or chlorine.

5. The compound according to any one of claims 1 to 3, wherein the ring comprising R8 and R9 is substituted by methyl or benzyl.

6. A compound of general formula (Ia) or (Ib) wherein R1 or R3 denotes hydrogen, C1-4-alkyl or benzyl;
R2 denotes hydrogen, C1-6-alkyl, cyclopentyl, cyclohexyl, cyclopentanone, cyclohexanone, hydroxycylopentane or hydrocyclohexane; a morpholine group optionally substituted by C1-4-alkyl; a piperidinyl group; a piperazinyl group optionally substituted by benzyl or C1-4-alkyl; pyridyl; tetrahydrofuranyl; tetrahydropyranyl;
furyl; a phenyl group optionally substituted by any of C1-4-alkyl, halogen and hydroxy; a phenyl-C1-4-alkyl, wherein the phenyl ring is optionally substituted by any of halogen, C1-4-alkyl, C1-4-alkyloxy, hydroxy and NR8R9; an amine of general formula NR8R9; or norbornenyl, norbornyl, adamantyl or noradamantyl optionally substituted by C1-4-alkyl;

R4 denotes C1-7-alkyl, or phenyl-C1-3-alkyl, wherein the phenyl ring is optionally substituted by any of halogen, hydroxy, C1-4-alkyl, C1-4-alkyloxy and NR8R9;

R6 denotes hydrogen, or C1-6-alkyl wherein the alkyl chain is optionally substituted by any of halogen, hydroxy, =O, C1-4-alkyloxy, NR8R9, phenyloxy, -O-phenyl-O-C1-4-alkyloxy, benzyloxy, -O-benzyl-O-C1-4-alkyloxy, -OCO-C1-4-alkyl, -OCO-phenyl, -OCO-pyridyl, -OCO-benzyl, -O-C2-4-alkylene, -CO-C1-4-alkyl, -CHO, =NOH, -COOH, -COO-C1-4-alkyl, -COO-phenyl, -COO-benzyl, -CONR8R9, -NHCO-C1-4-alkyl, -NHCO-phenyl, -CO-C1-4-alkyl-NR8R9, -SO2OH, -SO2-C1-4-alkyl and -SO2-phenyl; phenyl, optionally substituted by any of halogen, hydroxy, C1-4-alkyl, C1-4-alkyloxy and NR8R9;

phenyl-C1-3-alkyl, wherein the phenyl ring is optionally substituted by any of halogen, hydroxy, C1-4-alkyl, C1-4-alkyloxy, benzyloxy, phenyloxy, -NR8R9, -OCO-C1-4-alkyl, -OCO-phenyl, -OCO-benzyl, -OCO-pyridyl, -O-C2-4-alkylene, -CO-C1-4-alkyl, -C1-4-alkyl-NR8R9, -C1-4-alkyl-OH, -C1-4-alkyl=NOH, -COOH, -COO-C1-4-alkyl, -COO-phenyl, -COO-benzyl, -CONR8R9, -CO-C1-4-alkyl-NR8R9, -SO2OH, -SO2-C1-4-alkyl and -SO2-phenyl; any of cyclopentyl, cyclohexyl, cyclohexyl-C1-3-alkyl, cyclopentanone, cyclohexanone, hydroxycyclopentane and hydroxycyclohexane linked to the rest of the compound via a single bond or via a C1-4-alkylene chain; any one of furan, tetrahydrofuran, .alpha.-pyran, .gamma.-pyran, dioxolane, tetrahydropyran, dioxane, thiophene, thiolane, dithiolane, pyrrole, pyrroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, triazine, morpholine, thiomorpholine, oxazole, isoxazole, oxazine, thiazole, isothiazole, thiadiazole, oxadiazole and pyrazolidine linked to the rest of the compound via a single bond or via a C1-4-alkylene chain; any one of -CHO, -COOH, -COO-C1-4-alkyl, -COO-phenyl, -COO-benzyl, -CO-NH-C1-4-alkyl, -CO-N(C1-4-alkyl)2 and -CO-NH-phenyl; or an amine of general formula NR8R9;

R8 denotes hydrogen, or a branched or unbranched 15 C1-4-alkyl group; or any one of a C-linked pyrrole, pyrroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, morpholine, oxazole, isoxazole, thiazole, isothiazole and thiadiazole optionally substituted by any of chlorine, bromine, C1-4-alkyl, C1-4-alkyloxy, -NO2, -NH2 and -OH; and R9 denotes hydrogen, or a branched or unbranched C1-4-alkyl group; or any one of a C-linked pyrrole, pyrroline, pyrrolidine, pyrazole, pyrazoline, imidazole, imidazoline, imidazolidine, triazole, pyridine, piperidine, pyridazine, pyrimidine, pyrazine, piperazine, morpholine, oxazole, isoxazole, thiazole, isothiazole and thiadiazole optionally substituted by any of chlorine, bromine, C1-4-alkyl, C1-4-alkyloxy, -NO2, -NH2, and -OH; or R8 and R9 together with the nitrogen atom in NR8R9 form a saturated or unsaturated 5- or 6-membered ring optionally substituted by a branched or unbranched C1-4-alkyl group, or by a -(CH2)1-4 -phenyl group;

or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.

7. The compound according to claim 6, wherein R8 and R9, together with the nitrogen atom in NR8R9, form a saturated or unsaturated 5- or 6-membered ring comprising one or more additional heteroatoms selected from oxygen and nitrogen.

8. The compound according to claim 6 or 7, wherein R2 is fluorine or chlorine substituted phenyl-C1-6-alkyl, phenyl-C2-6-alkenyl or phenyl-C2-6-alkynyl.

9. The compound according to any one of claims 6 to 8, wherein R4 is benzyl wherein the phenyl ring is optionally substituted by any of halogen, hydroxy, C1-4-alkyl, C1-4-alkyloxy and NR8R9.

10. The compound according to any one of claims 6 to 9, wherein R6 is phenyl-C1-3-alkyl, wherein the phenyl ring is substituted by fluorine or chlorine; or wherein R6 is cyclohexylmethyl.

11. A compound of general formula (Ib) (Ib) wherein R2 denotes hydrogen, C1-4-alkyl, phenyl, or benzyl, wherein the phenyl ring of the benzyl is optionally fluorine-substituted, pyridyl, piperidinyl, morpholinyl, piperazinyl, 4-benzylpiperazinyl, furyl, tetrahydrofuranyl, tetrahydropyranyl, NR8R9, cyclopentyl, cyclohexyl, adamantyl, noradamantyl, norbornyl or norbornenyl;

R3 denotes hydrogen, C1-3-alkyl or benzyl;
R4 denotes C1-5-alkyl or benzyl;
R6 denotes hydrogen, C1-4-alkyl; C1-4-alkyl optionally substituted by any of OH, chlorine, bromine, C1-4-alkyloxy and NR8R9; -CHO, -COOH, -COO-C1-4-alkyl, phenyl, phenyl-C1-3-alkyl optionally substituted by fluorine or benzyloxy, optionally methoxy-substituted phenyloxy-C1-3-alkyl, optionally methoxy-substituted benzyloxy-C1-3-alkyl, benzyloxybenzyl, benzoyloxymethyl, pyridylcarbonyloxymethyl, cyclopentyl, furyl, cyclohexylmethyl, pyridylmethyl, N-pyrrolylmethyl or N-morpholinomethyl;

R8 denotes hydrogen, C1-4-alkyl or pyridyl; and R9 denotes hydrogen, C1-4-alkyl or pyridyl;
or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.

12. A compound of general formula (Ia) (Ia) wherein R1 denotes hydrogen, C1-3-alkyl or benzyl;

R2 denotes hydrogen, C1-4-alkyl, phenyl, benzyl, wherein the phenyl ring of the benzyl is optionally fluorine-substituted, pyridyl, piperidinyl, morpholinyl, piperazinyl, 4-benzylpiperazinyl, furyl, tetrahydrofuranyl, tetrahydropyranyl, NR8R9, cyclopentyl, cyclohexyl, adamantyl, noradamantyl, norbornyl or norbornenyl;

R4 denotes C1-5-alkyl or benzyl;

R6 denotes hydrogen, C1-4-alkyl optionally substituted by any of OH, chlorine, bromine, C1-4-alkyloxy and NR8R9, -CHO, -COOH, -COO-C1-4-alkyl, phenyl, phenyl-C1-3-alkyl optionally substituted by fluorine or benzyloxy, optionally methoxy-substituted phenyloxy-C1-3-alkyl, optionally methoxy-substituted benzyloxy-C1-3-alkyl, benzyloxybenzyl, benzoyloxymethyl, pyridylcarbonyloxymethyl, cyclopentyl, furyl, cyclohexylmethyl, pyridylmethyl, N-pyrrolylmethyl or N-morpholinomethyl;

R8 denotes hydrogen, C1-4-alkyl or pyridyl; and R9 denotes hydrogen, C1-4-alkyl or pyridyl;

or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.

13. A compound of general formula (Ic) wherein R1 denotes hydrogen or C1-3-alkyl;
R2 denotes hydrogen, C1-4-alkyl, cyclopentyl, cyclopentanone, hydroxycyclopentane, furan or benzyl;
R5 denotes C1-6-alkyl; and R6 denotes hydrogen, benzyl or cyclopentyl;
or a racemate enantiomer or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.

14. A compound of general formula (Id) wherein R3 denotes hydrogen or C1-3-alkyl;
R2 denotes hydrogen, C1-4-alkyl, cyclopentyl, cyclopentanone, hydroxycyclopentane, furan or benzyl;
R5 denotes C1-6-alkyl; and R6 denotes hydrogen, benzyl or cyclopentyl;
or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.

15. A compound of general formula (Ib) wherein R2 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 2-furyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMe2, cyclopentyl, cyclohexyl, adamantan-1-yl, noradmantan-3-yl, norbornan-2-yl or 5-norbornen-2-yl;
R3 denotes hydrogen, methyl, ethyl, n-propyl or benzyl;
R4 denotes methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, n-pentyl or benzyl; and R6 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl)-NH-CH2-, Ph-CO-O-CH2-, pyridyl-CO-O-CH2-, Ph-O-CH2-, (4-MeO-Ph) -O-CH2-, (4-MeO-Ph) -CH2-O-CH2-, (4-Ph-CH2-O-Ph) -CH2-, 4-F-Ph-CH2-, 3,4-F-Ph-CH2-, -COOH, -COOMe, -CH2-OH, -CH2-OMe, -CH2OEt or -CH2-NMe2;
or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.

16. A compound of general formula (Ia) wherein R1 denotes hydrogen, methyl, ethyl, n-propyl or benzyl;
R2 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, 4-fluorobenzyl, pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 2-furyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMe2, cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norbornan-2-yl or 5-norbornen-2-yl;
R4 denotes methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, n-pentyl or benzyl; and R6 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl)-NH-CH2-, Ph-CO-O-CH2-, pyridyl-CO-O-CH2-, Ph-O-CH2-, (4-MeO-Ph)-O-CH2-, (4-MeO-Ph)-CH2-O-CH2-, (4-Ph-CH2-O-Ph) -CH2-, 4-F-Ph-CH2-, 3,4-F-Ph-CH2-, -COOH, -COOMe, -CH2-OH, -CH2-OMe, -CH2OEt or -CH2-NMe2:
or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.

17. A compound of general formula (Ib) wherein R2 denotes hydrogen, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, 2-pyridyl, 3-pyridyl 4-pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 3-tetrahydrofuranyl, 4-tetrahydropyranyl, -NMe2, cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norbornan-2-yl or 5-norbornen-2-yl;
R3 denotes hydrogen;
R4 denotes methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, n-pentyl or benzyl; and R6 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, 2-phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl)-NH-CH2-, Ph-COO-CH2-, 3-pyridyl-COO-CH2-Ph-O-CH2-, (4-MeO-Ph)-O-CH2-, (4-MeO-Ph)-CH2-O-CH2-, 4-F-Ph-CH2-, 3,4-F-Ph-CH2-, -CH2-OH, -CH2-OMe, -CH2-OEt, -CH2-NMe2, -COOMe or -COOH;
or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.

18. A compound of general formula (Ia) wherein R1 denotes hydrogen;
R2 denotes hydrogen, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, N-piperidinyl, N-morpholinyl, N-piperazinyl, 4-benzylpiperazinyl, 3-tetrahyydrofuranyl, 4-tetrahydropyranyl, -NMe2, cyclopentyl, cyclohexyl, adamantan-1-yl, noradamantan-3-yl, norbornan-2-yl or 5-norbornen-2-yl;
R4 denotes methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, n-pentyl or benzyl; and R6 denotes hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, tert.-butyl, phenyl, benzyl, cyclopentyl, 2-furyl, 2-pyridylmethyl, 3-pyridylmethyl, 4-pyridylmethyl, cyclohexylmethyl, 2-phenylethyl, N-morpholinomethyl, N-pyrrolylmethyl, (3-pyridyl)-NH-CH2-, Ph-COO-CH2-, 3-pyridyl-COO-CH2-, Ph-O-CH2-, (4-MeO-Ph) -OCH2-, (4-MeO-Ph)-CH2-O-CH2, 4-F-Ph-CH2-, 3,4-F-Ph-CH2-, -CH2-OH, -CH2-OMe, -CH2-OEt, -CH2-NMe2, -COOMe or -COOH;
or a racemate, enantiomer, or diastereomer of the compound or a mixture of racemates, enantiomers or diastereomers of the compound; or a pharmacologically acceptable acid addition salt of the compound.

19. A use of a compound according to any one of claims 1 to 18 in the preparation of a medicament having adenosine-antagonistic activity.

20. A use of a compound according to any one of claims 1 to 18 in the treatment of a disease or a pathological situation connected with the activation of an adenosine receptor.

21. A use of a compound according to any one of claims 1 to 18 in the treatment of a degenerative disease of the central nervous system.

22. The use according to claim 21, wherein the disease is selected from the group consisting of senile dementia of the Alzheimer's type, and age-associated disorders of memory and learning performance.

23. The use according to claim 21, wherein the disease is selected from the group consisting of sleep disorders, motor-coordination disorders, Parkinson's disease, lability, migraine, depression, asthma, cardiovascular disease, kidney disease; diseases and pathological situations associated with mast cell degranulation; and cystic fibrosis.

24. A pharmaceutical composition comprising an effective amount of one or more compounds according to any one of claims 1 to 18 or a physiologically acceptable acid addition salt thereof, and a pharmaceutically acceptable excipient, carrier or diluent.

25. The pharmaceutical composition according to claim 24, for the treatment of a disease or a pathological situation connected with the activation of an adenosine receptor.

26. The pharmaceutical composition according to claim 24 for the treatment of a degenerative disease of the central nervous system.

27. The pharmaceutical composition according to claim 26, wherein the disease is selected from the group consisting of senile dementia of the Alzheimer's type, age-associated disorders of memory and learning disorders.

28. The pharmaceutical composition according to claim 26, wherein the disease is selected from the group consisting of sleep disorders, motor-coordination disorders, Parkinson's disease, lability, migraine, depression, asthma, cardiovascular disease, kidney disease; diseases and pathological situations associated with mast cell degeneration; and cystic fibrosis.

29. A process for preparing a compound of any one of formulae Ia to Id as shown in claim 1, wherein R1, R2, R3, R4, R5 and R6 are defined as in any one of claims 1 to 18, wherein:

a) a compound of general formula (9) or a tautomer thereof, wherein R2, R4 and R6 are as hereinbefore defined, is reacted in a suitable organic solvent or mixture of solvents under basic conditions with a suitable alkylating agent of general formula R1-X or R3-X, wherein R1 and R3 are as hereinbefore defined and X denotes a leaving group, or b) a compound of general formula (16) or a tautomer thereof, wherein R2, R5 and R6 are as hereinbefore defined, is reacted in a suitable organic solvent or mixture of solvents under basic conditions with a suitable alkylating agent of general formula R1-X or R3-X, wherein R1 and R3 are as hereinbefore defined and X denotes a leaving group, or c) for R4=R1 a compound of general formula or a tautomer thereof, wherein R2 and R6 are as hereinbefore defined, is reacted in a suitable organic solvent or mixture of solvents under basic conditions with a suitable alkylating agent of general formula R1-X or R3-X to form the monoalkylated compound (9) or directly to form any one of the dialkylated compounds Ia to Id, wherein R1 and R3 are as hereinbefore defined and X denotes a leaving group.

30. A process for preparing an imidazotriazolopyrimidinone derivative of general formula (9) or a tautomer thereof, wherein R2, R4, R6, R8, and R9 are defined as in any one of claims 1 to 18, wherein:

a) a compound of general formula wherein R2, R4 and R6 are as hereinbefore defined, is cyclised under basic, acidic or dehydrating conditions to obtain the imidazotriazolopyrimidinone derivative of general formula (9), or b) for R2=H, a diamine of general formula ~

wherein R4 and R6 are as hereinbefore defined, is converted by thermal reaction with formamide into the imidazotriazolopyrimidinone derivative of general formula (9) , or c) for R2=NR8R9, wherein R8 and R9 are as hereinbefore defined, a nitroso compound of general formula wherein R4 and R6 are as hereinbefore defined, is reacted under dehydrating conditions with an N-formylamine to obtain the imidazotriazolopyrimidinone derivative of general formula (9).

31. A process for preparing an imidazotriazolopyrimidinone derivative of general formula (16) or a tautomer thereof, wherein R2, R5 and R6 are defined as in any one of claims 1 to 18, wherein:

a) a compound of general formula wherein R2, R5 and R6 are as hereinbefore defined, is cyclised under basic, acidic or dehydrating conditions to obtain the imidazotriazolopyrimidinone derivative of general formula (16), or b) for R2=H, a diamine of general formula wherein R5 and R6 are as hereinbefore defined, is converted by thermal reaction with formamide into the imidazotriazolopyrimidinone derivative of general formula (16) , or c) for R2=NR8R9 wherein R8 and R9 are as hereinbefore defined, a nitroso compound of general formula wherein R5 and R6 are as hereinbefore defined, is reacted with an N-formylamine under dehydrating conditions to obtain the imidazotriazolopyrimidinone derivative of general formula (16).