NO323752B1 - Nye tieno(2,3-d)pyrimidindioner, fremgangsmate for fremstilling derav, farmasoytisk preparat som inneholder slike, samt anvendelse derav i terapi. - Google Patents

Nye tieno(2,3-d)pyrimidindioner, fremgangsmate for fremstilling derav, farmasoytisk preparat som inneholder slike, samt anvendelse derav i terapi. Download PDF

Info

Publication number: NO323752B1
Authority: NO; Norway
Prior art keywords: methyl; methylpropyl; pyrimidine; dione; thieno
Prior art date: 1997-05-28

Application number

NO19995810A

Other languages

English (en)

Norwegian (no)

Other versions

NO995810D0 (no

NO995810L (no

Inventor

Matthew Perry

Phillip Thorne

Martin Cooper

David Ranulft Cheshire

David Donald

Mark Furber

Andrew Cooke

Original Assignee

Astrazeneca Ab

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1997-05-28

Filing date

1999-11-26

Publication date

2007-07-02

1999-11-26 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

1999-11-26 Publication of NO995810D0 publication Critical patent/NO995810D0/no

2000-01-27 Publication of NO995810L publication Critical patent/NO995810L/no

2007-07-02 Publication of NO323752B1 publication Critical patent/NO323752B1/no

Links

238000000034 method Methods 0.000 title claims abstract description 29
238000002360 preparation method Methods 0.000 title claims description 19
238000002560 therapeutic procedure Methods 0.000 title claims description 6
239000008194 pharmaceutical composition Substances 0.000 title abstract 2
150000008512 pyrimidinediones Chemical class 0.000 title 1
238000004519 manufacturing process Methods 0.000 claims abstract description 12
JGOOQALRLGHKIY-UHFFFAOYSA-N 1h-thieno[2,3-d]pyrimidine-2,4-dione Chemical class O=C1NC(=O)NC2=C1C=CS2 JGOOQALRLGHKIY-UHFFFAOYSA-N 0.000 claims abstract description 11
150000001875 compounds Chemical class 0.000 claims description 228
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 70
125000000446 sulfanediyl group Chemical group *S* 0.000 claims description 68
-1 amino, nitro, cyano, trifluoromethoxy, phenoxy Chemical group 0.000 claims description 62
125000000217 alkyl group Chemical group 0.000 claims description 41
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 34
125000001424 substituent group Chemical group 0.000 claims description 30
229910052757 nitrogen Inorganic materials 0.000 claims description 29
125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 27
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
150000003839 salts Chemical class 0.000 claims description 20
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 19
239000012453 solvate Substances 0.000 claims description 19
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
229910052739 hydrogen Inorganic materials 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 14
150000002367 halogens Chemical class 0.000 claims description 14
125000003118 aryl group Chemical group 0.000 claims description 12
229910052799 carbon Inorganic materials 0.000 claims description 12
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 11
125000004076 pyridyl group Chemical group 0.000 claims description 11
KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 10
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 10
238000006243 chemical reaction Methods 0.000 claims description 10
125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 claims description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 8
ICMGLRUYEQNHPF-UHFFFAOYSA-N Uraprene Chemical compound COC1=CC=CC=C1N1CCN(CCCNC=2N(C(=O)N(C)C(=O)C=2)C)CC1 ICMGLRUYEQNHPF-UHFFFAOYSA-N 0.000 claims description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
239000000825 pharmaceutical preparation Substances 0.000 claims description 8
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 7
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
125000003342 alkenyl group Chemical group 0.000 claims description 6
125000003545 alkoxy group Chemical group 0.000 claims description 6
239000004202 carbamide Substances 0.000 claims description 6
125000005544 phthalimido group Chemical group 0.000 claims description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 6
ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical compound [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 claims description 6
FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 claims description 5
239000002671 adjuvant Substances 0.000 claims description 5
150000001540 azides Chemical class 0.000 claims description 5
125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
125000005518 carboxamido group Chemical group 0.000 claims description 5
239000003085 diluting agent Substances 0.000 claims description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 5
125000001624 naphthyl group Chemical group 0.000 claims description 5
125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
QDXGKRWDQCEABB-UHFFFAOYSA-N pyrimidine-5-carboxamide Chemical compound NC(=O)C1=CN=CN=C1 QDXGKRWDQCEABB-UHFFFAOYSA-N 0.000 claims description 5
125000005493 quinolyl group Chemical group 0.000 claims description 5
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 4
HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 claims description 4
230000015572 biosynthetic process Effects 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 4
WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 4
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
SPXBNLITJKGNON-UHFFFAOYSA-N 5-(3-aminophenyl)sulfanyl-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CC=2C3=CC=CC=C3C=CC=2)=C1SC1=CC=CC(N)=C1 SPXBNLITJKGNON-UHFFFAOYSA-N 0.000 claims description 3
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
229910006074 SO2NH2 Inorganic materials 0.000 claims description 3
125000004062 acenaphthenyl group Chemical group C1(CC2=CC=CC3=CC=CC1=C23)* 0.000 claims description 3
MJBWDEQAUQTVKK-IAGOWNOFSA-N aflatoxin M1 Chemical compound C=1([C@]2(O)C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O MJBWDEQAUQTVKK-IAGOWNOFSA-N 0.000 claims description 3
125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
125000003710 aryl alkyl group Chemical group 0.000 claims description 3
125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
125000000753 cycloalkyl group Chemical group 0.000 claims description 3
UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 3
125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 claims description 3
230000001506 immunosuppresive effect Effects 0.000 claims description 3
125000001041 indolyl group Chemical group 0.000 claims description 3
125000005956 isoquinolyl group Chemical group 0.000 claims description 3
230000003647 oxidation Effects 0.000 claims description 3
238000007254 oxidation reaction Methods 0.000 claims description 3
230000002441 reversible effect Effects 0.000 claims description 3
125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
CSQFBYFVSUVCOI-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-[(3-phenoxyphenyl)methyl]thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC=1CC(C=1)=CC=CC=1OC1=CC=CC=C1 CSQFBYFVSUVCOI-UHFFFAOYSA-N 0.000 claims description 2
SJZYZYMKFRJDEE-UHFFFAOYSA-N 5-(3-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2C(CC=3SC=4N(C(N(C)C(=O)C=4C=3SCCCO)=O)CC(C)C)=CC=CC2=C1 SJZYZYMKFRJDEE-UHFFFAOYSA-N 0.000 claims description 2
HOMDSZWWPIDRCP-UHFFFAOYSA-N 5-(3-methoxyphenyl)sulfanyl-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound COC1=CC=CC(SC=2C=3C(=O)N(C)C(=O)N(CC(C)C)C=3SC=2CC=2C3=CC=CC=C3C=CC=2)=C1 HOMDSZWWPIDRCP-UHFFFAOYSA-N 0.000 claims description 2
KVNIUXVYMKCDBZ-HXUWFJFHSA-N 5-[(3r)-3-hydroxypiperidine-1-carbonyl]-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=2C(=O)N(C)C(=O)N(CC(C)C)C=2SC(CC=2C3=CC=CC=C3C=CC=2)=C1C(=O)N1CCC[C@@H](O)C1 KVNIUXVYMKCDBZ-HXUWFJFHSA-N 0.000 claims description 2
DWWQYFABYPKNJL-UHFFFAOYSA-N 6-benzyl-3-methyl-1-propan-2-ylthieno[2,3-d]pyrimidine-2,4-dione Chemical compound C=1C=2C(=O)N(C)C(=O)N(C(C)C)C=2SC=1CC1=CC=CC=C1 DWWQYFABYPKNJL-UHFFFAOYSA-N 0.000 claims description 2
206010062016 Immunosuppression Diseases 0.000 claims description 2
101001043818 Mus musculus Interleukin-31 receptor subunit alpha Proteins 0.000 claims description 2
208000027771 Obstructive airways disease Diseases 0.000 claims description 2
MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 2
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
125000006626 methoxycarbonylamino group Chemical group 0.000 claims description 2
YEOWQQHHCCGIQH-UHFFFAOYSA-N methyl 4-[3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]sulfonylbutanoate Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3C=CC=1)=C2S(=O)(=O)CCCC(=O)OC YEOWQQHHCCGIQH-UHFFFAOYSA-N 0.000 claims description 2
238000002156 mixing Methods 0.000 claims description 2
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
NIRIGNIPEFMZHT-UHFFFAOYSA-N pyrimidine-5-sulfonamide Chemical compound NS(=O)(=O)C1=CN=CN=C1 NIRIGNIPEFMZHT-UHFFFAOYSA-N 0.000 claims description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims 1
CCJDJOGELWUHGZ-UHFFFAOYSA-N 2-hydroxyethyl n-[3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]carbamate Chemical compound C1=CC=C2C(CC=3SC=4N(C(N(C)C(=O)C=4C=3NC(=O)OCCO)=O)CC(C)C)=CC=CC2=C1 CCJDJOGELWUHGZ-UHFFFAOYSA-N 0.000 claims 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
FGISQWORLFKKQW-UHFFFAOYSA-N 5-(2-hydroxypropylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2C(CC=3SC=4N(C(N(C)C(=O)C=4C=3SCC(C)O)=O)CC(C)C)=CC=CC2=C1 FGISQWORLFKKQW-UHFFFAOYSA-N 0.000 claims 1
SMFPPUPRBSRENJ-UHFFFAOYSA-N 5-(3-hydroxybutylsulfanyl)-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2C(CC=3SC=4N(C(N(C)C(=O)C=4C=3SCCC(C)O)=O)CC(C)C)=CC=CC2=C1 SMFPPUPRBSRENJ-UHFFFAOYSA-N 0.000 claims 1
NBFPMPQACLXKNV-UHFFFAOYSA-N 6-(1-hydroxy-2,3-dihydroinden-1-yl)-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1CC2=CC=CC=C2C1(O)C(S1)=CC2=C1N(CC(C)C)C(=O)N(C)C2=O NBFPMPQACLXKNV-UHFFFAOYSA-N 0.000 claims 1
FGYULDUQQYWTDB-UHFFFAOYSA-N 6-[hydroxy(quinolin-3-yl)methyl]-3-methyl-1-(2-methylpropyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=CC2=CC(C(O)C=3SC=4N(C(N(C)C(=O)C=4C=3)=O)CC(C)C)=CN=C21 FGYULDUQQYWTDB-UHFFFAOYSA-N 0.000 claims 1
125000003341 7 membered heterocyclic group Chemical group 0.000 claims 1
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims 1
UTCPLRPOJZKOON-UHFFFAOYSA-N methyl n-[3-[3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]sulfanylpropyl]carbamate Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3C=CC=1)=C2SCCCNC(=O)OC UTCPLRPOJZKOON-UHFFFAOYSA-N 0.000 claims 1
HUSWLYKMRKMTFA-UHFFFAOYSA-N n-(2-hydroxyethyl)-3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)-2,4-dioxothieno[2,3-d]pyrimidine-5-carboxamide Chemical compound C1=CC=C2C(CC=3SC=4N(C(N(C)C(=O)C=4C=3C(=O)NCCO)=O)CC(C)C)=CC=CC2=C1 HUSWLYKMRKMTFA-UHFFFAOYSA-N 0.000 claims 1
DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims 1
235000019260 propionic acid Nutrition 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 295
239000000243 solution Substances 0.000 description 157
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 156
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 100
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 97
238000005481 NMR spectroscopy Methods 0.000 description 81
239000000203 mixture Substances 0.000 description 77
AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 70
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 70
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 63
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 62
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 60
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 51
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 50
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 48
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 46
239000000284 extract Substances 0.000 description 46
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 45
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 43
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 42
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 36
238000004440 column chromatography Methods 0.000 description 31
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 28
239000000377 silicon dioxide Substances 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
239000011541 reaction mixture Substances 0.000 description 25
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
239000007787 solid Substances 0.000 description 24
239000000725 suspension Substances 0.000 description 19
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 12
239000002904 solvent Substances 0.000 description 12
238000004305 normal phase HPLC Methods 0.000 description 11
229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
235000017557 sodium bicarbonate Nutrition 0.000 description 11
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
239000008346 aqueous phase Substances 0.000 description 10
239000012267 brine Substances 0.000 description 10
238000010992 reflux Methods 0.000 description 10
206010039083 rhinitis Diseases 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
238000004587 chromatography analysis Methods 0.000 description 9
229910052943 magnesium sulfate Inorganic materials 0.000 description 9
235000019341 magnesium sulphate Nutrition 0.000 description 9
239000012044 organic layer Substances 0.000 description 9
239000012071 phase Substances 0.000 description 9
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
238000000746 purification Methods 0.000 description 8
239000012279 sodium borohydride Substances 0.000 description 8
229910000033 sodium borohydride Inorganic materials 0.000 description 8
BVXSZFCQFRYKKE-UHFFFAOYSA-N 3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)thieno[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2C(CC=3SC=4N(C(N(C)C(=O)C=4C=3)=O)CC(C)C)=CC=CC2=C1 BVXSZFCQFRYKKE-UHFFFAOYSA-N 0.000 description 7
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
238000010828 elution Methods 0.000 description 7
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
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238000000921 elemental analysis Methods 0.000 description 1
230000003511 endothelial effect Effects 0.000 description 1
201000001564 eosinophilic gastroenteritis Diseases 0.000 description 1
231100000321 erythema Toxicity 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
JVLLJDNNOFFGCR-UHFFFAOYSA-N ethyl 2-[acetylcarbamoyl(2-methylpropyl)amino]-5-benzylthiophene-3-carboxylate Chemical compound S1C(N(CC(C)C)C(=O)NC(C)=O)=C(C(=O)OCC)C=C1CC1=CC=CC=C1 JVLLJDNNOFFGCR-UHFFFAOYSA-N 0.000 description 1
AGMKDPBSCDPQKG-UHFFFAOYSA-N ethyl 2-amino-5-(naphthalen-1-ylmethyl)thiophene-3-carboxylate Chemical compound S1C(N)=C(C(=O)OCC)C=C1CC1=CC=CC2=CC=CC=C12 AGMKDPBSCDPQKG-UHFFFAOYSA-N 0.000 description 1
STPXIOGYOLJXMZ-UHFFFAOYSA-N ethyl 2-oxo-4-phenylbutanoate Chemical compound CCOC(=O)C(=O)CCC1=CC=CC=C1 STPXIOGYOLJXMZ-UHFFFAOYSA-N 0.000 description 1
PTMUUPAAEHTYQV-UHFFFAOYSA-N ethyl 5-benzyl-2-(2-methylpropylamino)thiophene-3-carboxylate Chemical compound S1C(NCC(C)C)=C(C(=O)OCC)C=C1CC1=CC=CC=C1 PTMUUPAAEHTYQV-UHFFFAOYSA-N 0.000 description 1
FDLDWKIEWAWOSL-UHFFFAOYSA-N ethyl acetate;2-methylpentane Chemical compound CCCC(C)C.CCOC(C)=O FDLDWKIEWAWOSL-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
125000004494 ethyl ester group Chemical group 0.000 description 1
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
208000022195 farmer lung disease Diseases 0.000 description 1
YLQWCDOCJODRMT-UHFFFAOYSA-N fluoren-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C2=C1 YLQWCDOCJODRMT-UHFFFAOYSA-N 0.000 description 1
239000006260 foam Substances 0.000 description 1
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238000001640 fractional crystallisation Methods 0.000 description 1
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239000003102 growth factor Substances 0.000 description 1
210000002216 heart Anatomy 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
125000001183 hydrocarbyl group Chemical group 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
COQRGFWWJBEXRC-UHFFFAOYSA-N hydron;methyl 2-aminoacetate;chloride Chemical compound Cl.COC(=O)CN COQRGFWWJBEXRC-UHFFFAOYSA-N 0.000 description 1
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
206010051040 hyper-IgE syndrome Diseases 0.000 description 1
230000003463 hyperproliferative effect Effects 0.000 description 1
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230000008102 immune modulation Effects 0.000 description 1
230000028993 immune response Effects 0.000 description 1
208000026278 immune system disease Diseases 0.000 description 1
238000011534 incubation Methods 0.000 description 1
UMJJFEIKYGFCAT-UHFFFAOYSA-N indan-2-one Chemical compound C1=CC=C2CC(=O)CC2=C1 UMJJFEIKYGFCAT-UHFFFAOYSA-N 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
210000003734 kidney Anatomy 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
201000010260 leiomyoma Diseases 0.000 description 1
201000011486 lichen planus Diseases 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
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210000004185 liver Anatomy 0.000 description 1
206010025135 lupus erythematosus Diseases 0.000 description 1
CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
238000004949 mass spectrometry Methods 0.000 description 1
208000008585 mastocytosis Diseases 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
JCZWCUDKNNBEEM-UHFFFAOYSA-N methyl 4-[3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]sulfanylbutanoate Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3C=CC=1)=C2SCCCC(=O)OC JCZWCUDKNNBEEM-UHFFFAOYSA-N 0.000 description 1
GPKCPCQMWLQCOX-UHFFFAOYSA-N methyl 4-[3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]sulfinylbutanoate Chemical compound CC(C)CN1C(=O)N(C)C(=O)C2=C1SC(CC=1C3=CC=CC=C3C=CC=1)=C2S(=O)CCCC(=O)OC GPKCPCQMWLQCOX-UHFFFAOYSA-N 0.000 description 1
244000000010 microbial pathogen Species 0.000 description 1
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201000006417 multiple sclerosis Diseases 0.000 description 1
206010028417 myasthenia gravis Diseases 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
BYSITHLECVQPQP-UHFFFAOYSA-N n-[3-[3-methyl-1-(2-methylpropyl)-6-(naphthalen-1-ylmethyl)-2,4-dioxothieno[2,3-d]pyrimidin-5-yl]sulfanylpropyl]acetamide Chemical compound C1=CC=C2C(CC=3SC=4N(C(N(C)C(=O)C=4C=3SCCCNC(C)=O)=O)CC(C)C)=CC=CC2=C1 BYSITHLECVQPQP-UHFFFAOYSA-N 0.000 description 1
NSNPSJGHTQIXDO-UHFFFAOYSA-N naphthalene-1-carbonyl chloride Chemical compound C1=CC=C2C(C(=O)Cl)=CC=CC2=C1 NSNPSJGHTQIXDO-UHFFFAOYSA-N 0.000 description 1
UFWIBTONFRDIAS-UHFFFAOYSA-N naphthalene-acid Natural products C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 1
125000006501 nitrophenyl group Chemical group 0.000 description 1
230000000414 obstructive effect Effects 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
125000003431 oxalo group Chemical group 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
239000008188 pellet Substances 0.000 description 1
229940049954 penicillin Drugs 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
239000012286 potassium permanganate Substances 0.000 description 1
OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
239000000047 product Substances 0.000 description 1
230000002062 proliferating effect Effects 0.000 description 1
ZJLMKPKYJBQJNH-UHFFFAOYSA-N propane-1,3-dithiol Chemical compound SCCCS ZJLMKPKYJBQJNH-UHFFFAOYSA-N 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
DKORSYDQYFVQNS-UHFFFAOYSA-N propyl methanesulfonate Chemical compound CCCOS(C)(=O)=O DKORSYDQYFVQNS-UHFFFAOYSA-N 0.000 description 1
239000013014 purified material Substances 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
NFKXXURQUMEXDJ-UHFFFAOYSA-N pyrimidine-5-carbonyl chloride Chemical compound ClC(=O)C1=CN=CN=C1 NFKXXURQUMEXDJ-UHFFFAOYSA-N 0.000 description 1
IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 description 1
230000006340 racemization Effects 0.000 description 1
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230000001105 regulatory effect Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
201000000306 sarcoidosis Diseases 0.000 description 1
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238000000926 separation method Methods 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
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229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
229940001584 sodium metabisulfite Drugs 0.000 description 1
235000010262 sodium metabisulphite Nutrition 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
201000005671 spondyloarthropathy Diseases 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
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238000007920 subcutaneous administration Methods 0.000 description 1
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239000000829 suppository Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
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201000000596 systemic lupus erythematosus Diseases 0.000 description 1
239000003826 tablet Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
GAEQFCXLHIDNDY-UHFFFAOYSA-N tert-butyl-[1-[2-[tert-butyl(dimethyl)silyl]oxypropyldisulfanyl]propan-2-yloxy]-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OC(C)CSSCC(C)O[Si](C)(C)C(C)(C)C GAEQFCXLHIDNDY-UHFFFAOYSA-N 0.000 description 1
UQCWXKSHRQJGPH-UHFFFAOYSA-M tetrabutylazanium;fluoride;hydrate Chemical compound O.[F-].CCCC[N+](CCCC)(CCCC)CCCC UQCWXKSHRQJGPH-UHFFFAOYSA-M 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
YNVOMSDITJMNET-UHFFFAOYSA-N thiophene-3-carboxylic acid Chemical compound OC(=O)C=1C=CSC=1 YNVOMSDITJMNET-UHFFFAOYSA-N 0.000 description 1
229940104230 thymidine Drugs 0.000 description 1
230000002103 transcriptional effect Effects 0.000 description 1
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238000005292 vacuum distillation Methods 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A—HUMAN NECESSITIES
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- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Animal Behavior & Ethology (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Immunology (AREA)
Pulmonology (AREA)
Rheumatology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Dermatology (AREA)
Virology (AREA)
AIDS & HIV (AREA)
Orthopedic Medicine & Surgery (AREA)
Cardiology (AREA)
Heart & Thoracic Surgery (AREA)
Transplantation (AREA)
Pain & Pain Management (AREA)
Urology & Nephrology (AREA)
Molecular Biology (AREA)
Tropical Medicine & Parasitology (AREA)
Vascular Medicine (AREA)
Physical Education & Sports Medicine (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Use Of Switch Circuits For Exchanges And Methods Of Control Of Multiplex Exchanges (AREA)
Valve-Gear Or Valve Arrangements (AREA)
Liquid Crystal (AREA)

NO19995810A 1997-05-28 1999-11-26 Nye tieno(2,3-d)pyrimidindioner, fremgangsmate for fremstilling derav, farmasoytisk preparat som inneholder slike, samt anvendelse derav i terapi. NO323752B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
SE9702001A SE9702001D0 (sv)	1997-05-28	1997-05-28	Novel compounds
PCT/SE1998/000935 WO1998054190A1 (en)	1997-05-28	1998-05-18	Novel compounds

Publications (3)

Publication Number	Publication Date
NO995810D0 NO995810D0 (no)	1999-11-26
NO995810L NO995810L (no)	2000-01-27
NO323752B1 true NO323752B1 (no)	2007-07-02

Family

ID=20407123

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19995810A NO323752B1 (no)	1997-05-28	1999-11-26	Nye tieno(2,3-d)pyrimidindioner, fremgangsmate for fremstilling derav, farmasoytisk preparat som inneholder slike, samt anvendelse derav i terapi.

Country Status (28)

Country	Link
US (2)	US6180635B1 (da)
EP (1)	EP0991653B1 (da)
JP (1)	JP2002500666A (da)
KR (1)	KR100561988B1 (da)
CN (1)	CN1122037C (da)
AT (1)	ATE226205T1 (da)
AU (1)	AU723708B2 (da)
BR (1)	BR9809481A (da)
CA (1)	CA2289509C (da)
CZ (1)	CZ297536B6 (da)
DE (1)	DE69808765T2 (da)
DK (1)	DK0991653T3 (da)
EE (1)	EE04018B1 (da)
ES (1)	ES2184270T3 (da)
HU (1)	HU226627B1 (da)
ID (1)	ID28432A (da)
IL (2)	IL132763A0 (da)
IS (1)	IS1983B (da)
NO (1)	NO323752B1 (da)
NZ (1)	NZ500853A (da)
PL (1)	PL199567B1 (da)
PT (1)	PT991653E (da)
RU (1)	RU2225410C2 (da)
SE (1)	SE9702001D0 (da)
SK (1)	SK283589B6 (da)
TR (1)	TR199902904T2 (da)
UA (1)	UA61111C2 (da)
WO (1)	WO1998054190A1 (da)

Families Citing this family (41)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
SE9801399D0 (sv)	1998-04-21	1998-04-21	Astra Pharma Prod	Method and apparatus for filling containers
GB9819382D0 (en) *	1998-09-04	1998-10-28	Cerebrus Ltd	Chemical compounds I
GB9819384D0 (en)	1998-09-04	1998-10-28	Cerebrus Ltd	Chemical compounds II
GB2361917A (en) *	2000-05-04	2001-11-07	Astrazeneca Ab	Novel thieno[2,3-d]pyrimidinediones
JP2003531910A (ja) *	2000-05-04	2003-10-28	アストラゼネカアクチボラグ	チエノ［２，３−ｄ］ピリミジンジオン類とそれらの医薬品としての使用
GB2363377B (en) *	2000-06-14	2004-06-09	Astrazeneca Ab	Novel thieno[2,3-d]pyrimidinediones and therapeutic uses thereof
CA2433778A1 (en) *	2001-02-14	2002-08-22	William Glen Harter	Thieno'2,3-d pyrimidindione derivatives as matrix metalloproteinase inhibitors
GB0117583D0 (en) *	2001-07-19	2001-09-12	Astrazeneca Ab	Novel compounds
GB0118479D0 (en) *	2001-07-28	2001-09-19	Astrazeneca Ab	Novel compounds
BR0215212A (pt) *	2001-12-21	2004-12-07	Novo Nordisk As	Ativador de carboxamida ou sulfonamida de glicoquinase, composto, composição farmacêutica, e, uso de um composto
CA2744893A1 (en) *	2002-06-27	2004-01-08	Novo Nordisk A/S	Aryl carbonyl derivatives as glucokinase activators
US6890923B2 (en) *	2002-12-16	2005-05-10	Astrazeneca Ab	Compounds
SE0300120D0 (sv)	2003-01-17	2003-01-17	Astrazeneca Ab	Novel compounds
SE0300117D0 (sv) *	2003-01-17	2003-01-17	Astrazeneca Ab	Novel Compounds
SE0300119D0 (sv) *	2003-01-17	2003-01-17	Astrazeneca Ab	Novel compounds
BRPI0406782A (pt)	2003-01-17	2006-01-17	Astrazeneca Ab	Derivados de tieno-piridazinonas e seu uso na modulação de doenças autoimunes
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1997
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- 1998-05-18 DE DE69808765T patent/DE69808765T2/de not_active Expired - Fee Related
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Also Published As

Publication number	Publication date
PL337126A1 (en)	2000-07-31
HUP0003355A3 (en)	2003-03-28
UA61111C2 (uk)	2003-11-17
CZ420199A3 (cs)	2000-07-12
IS5264A (is)	1999-11-23
EE9900539A (et)	2000-06-15
CZ297536B6 (cs)	2007-01-03
PL199567B1 (pl)	2008-10-31
AU7680898A (en)	1998-12-30
SE9702001D0 (sv)	1997-05-28
ES2184270T3 (es)	2003-04-01
US6180635B1 (en)	2001-01-30
RU2225410C2 (ru)	2004-03-10
BR9809481A (pt)	2000-06-20
DK0991653T3 (da)	2003-01-06
IL132763A0 (en)	2001-03-19
DE69808765D1 (de)	2002-11-21
SK283589B6 (sk)	2003-10-07
NO995810D0 (no)	1999-11-26
IL132763A (en)	2007-03-08
ID28432A (id)	2001-05-24
KR20010013107A (ko)	2001-02-26
NZ500853A (en)	2001-05-25
DE69808765T2 (de)	2003-07-24
PT991653E (pt)	2003-02-28
CA2289509A1 (en)	1998-12-03
JP2002500666A (ja)	2002-01-08
EP0991653B1 (en)	2002-10-16
IS1983B (is)	2005-01-14
SK151399A3 (en)	2000-05-16
CA2289509C (en)	2007-10-02
CN1122037C (zh)	2003-09-24
HU226627B1 (en)	2009-05-28
HUP0003355A2 (hu)	2001-02-28
ATE226205T1 (de)	2002-11-15
KR100561988B1 (ko)	2006-03-17
WO1998054190A1 (en)	1998-12-03
US6342502B1 (en)	2002-01-29
EP0991653A1 (en)	2000-04-12
AU723708B2 (en)	2000-09-07
CN1264382A (zh)	2000-08-23
NO995810L (no)	2000-01-27
EE04018B1 (et)	2003-04-15
TR199902904T2 (xx)	2000-06-21

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