NO322094B1 - Bicykliske heterocykler, medikamenter inneholdende disse forbindelser, deres anvendelse og fremgangsmate for fremstilling av dem. - Google Patents

Bicykliske heterocykler, medikamenter inneholdende disse forbindelser, deres anvendelse og fremgangsmate for fremstilling av dem. Download PDF

Info

Publication number: NO322094B1
Authority: NO; Norway
Prior art keywords: group; amino; alkyl; methyl; substituted
Prior art date: 1999-06-21

Application number

NO20016185A

Other languages

English (en)

Norwegian (no)

Other versions

NO20016185D0 (no

NO20016185L (no

Inventor

Frank Himmelsbach

Thomas Metz

Elke Langkopf

Flavio Solca

Anke Baum

Birgit Jung

Original Assignee

Boehringer Ingelheim Pharma

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.)

1999-06-21

Filing date

2001-12-18

Publication date

2006-08-14

1999-06-21 Priority claimed from DE1999128281 external-priority patent/DE19928281A1/de

2000-05-11 Priority claimed from DE2000123085 external-priority patent/DE10023085A1/de

2001-12-18 Application filed by Boehringer Ingelheim Pharma filed Critical Boehringer Ingelheim Pharma

2001-12-18 Publication of NO20016185D0 publication Critical patent/NO20016185D0/no

2001-12-18 Publication of NO20016185L publication Critical patent/NO20016185L/no

2006-08-14 Publication of NO322094B1 publication Critical patent/NO322094B1/no

Links

150000001875 compounds Chemical class 0.000 title claims description 74
125000002618 bicyclic heterocycle group Chemical group 0.000 title claims description 7
238000000034 method Methods 0.000 title claims description 7
238000002360 preparation method Methods 0.000 title description 11
239000003814 drug Substances 0.000 title description 7
229940079593 drug Drugs 0.000 title description 4
-1 1,2-vinylene group Chemical group 0.000 claims description 269
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 150
229910052757 nitrogen Inorganic materials 0.000 claims description 50
125000004433 nitrogen atom Chemical group N* 0.000 claims description 42
125000000217 alkyl group Chemical group 0.000 claims description 34
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
150000003839 salts Chemical class 0.000 claims description 29
125000003277 amino group Chemical group 0.000 claims description 23
238000006243 chemical reaction Methods 0.000 claims description 20
125000002947 alkylene group Chemical group 0.000 claims description 18
125000001841 imino group Chemical group [H]N=* 0.000 claims description 18
238000004519 manufacturing process Methods 0.000 claims description 18
125000004432 carbon atom Chemical group C* 0.000 claims description 16
229910052799 carbon Inorganic materials 0.000 claims description 15
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
125000003282 alkyl amino group Chemical group 0.000 claims description 13
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
201000010099 disease Diseases 0.000 claims description 11
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 9
239000000460 chlorine Substances 0.000 claims description 9
229910052801 chlorine Inorganic materials 0.000 claims description 9
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 9
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
125000003545 alkoxy group Chemical group 0.000 claims description 8
229910052731 fluorine Inorganic materials 0.000 claims description 8
239000011737 fluorine Substances 0.000 claims description 8
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 8
229910052717 sulfur Inorganic materials 0.000 claims description 8
MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 7
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 7
229910052760 oxygen Inorganic materials 0.000 claims description 7
239000001301 oxygen Substances 0.000 claims description 7
125000006239 protecting group Chemical group 0.000 claims description 7
125000001424 substituent group Chemical group 0.000 claims description 7
125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 7
125000004434 sulfur atom Chemical group 0.000 claims description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims description 6
125000004430 oxygen atom Chemical group O* 0.000 claims description 6
210000002345 respiratory system Anatomy 0.000 claims description 5
125000002252 acyl group Chemical group 0.000 claims description 4
230000010933 acylation Effects 0.000 claims description 4
238000005917 acylation reaction Methods 0.000 claims description 4
150000001408 amides Chemical class 0.000 claims description 4
150000001412 amines Chemical class 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
150000002148 esters Chemical class 0.000 claims description 4
239000000825 pharmaceutical preparation Substances 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 3
230000029936 alkylation Effects 0.000 claims description 3
238000005804 alkylation reaction Methods 0.000 claims description 3
125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 3
239000000969 carrier Substances 0.000 claims description 3
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
239000003085 diluting agent Substances 0.000 claims description 3
230000032050 esterification Effects 0.000 claims description 3
238000005886 esterification reaction Methods 0.000 claims description 3
210000004072 lung Anatomy 0.000 claims description 3
150000007522 mineralic acids Chemical class 0.000 claims description 3
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 3
150000007524 organic acids Chemical class 0.000 claims description 3
235000005985 organic acids Nutrition 0.000 claims description 3
238000005932 reductive alkylation reaction Methods 0.000 claims description 3
230000006103 sulfonylation Effects 0.000 claims description 3
238000005694 sulfonylation reaction Methods 0.000 claims description 3
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical group [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 2
210000000013 bile duct Anatomy 0.000 claims description 2
229910052794 bromium Inorganic materials 0.000 claims description 2
201000011510 cancer Diseases 0.000 claims description 2
125000000062 cyclohexylmethoxy group Chemical group [H]C([H])(O*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
125000004185 ester group Chemical group 0.000 claims description 2
125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
210000000232 gallbladder Anatomy 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
ARFWPHOPKFABNZ-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-(diethylamino)but-2-enamide Chemical compound N1=CN=C2C=C(OCC3CC3)C(NC(=O)C=CCN(CC)CC)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ARFWPHOPKFABNZ-UHFFFAOYSA-N 0.000 claims description 2
FBZNVWCZYHHTSH-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-[3-(1-methylpiperidin-4-yl)propoxy]quinazolin-6-yl]prop-2-enamide Chemical compound C1CN(C)CCC1CCCOC1=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C2C=C1NC(=O)C=C FBZNVWCZYHHTSH-UHFFFAOYSA-N 0.000 claims description 2
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
230000002265 prevention Effects 0.000 claims description 2
125000005505 thiomorpholino group Chemical group 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
210000002784 stomach Anatomy 0.000 claims 1
239000011593 sulfur Substances 0.000 claims 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 219
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 174
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 147
238000001819 mass spectrum Methods 0.000 description 90
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 80
239000000741 silica gel Substances 0.000 description 78
229910002027 silica gel Inorganic materials 0.000 description 78
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 57
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 45
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 36
238000002844 melting Methods 0.000 description 35
230000008018 melting Effects 0.000 description 35
239000002904 solvent Substances 0.000 description 29
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 28
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 28
235000011114 ammonium hydroxide Nutrition 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
239000000243 solution Substances 0.000 description 25
239000013543 active substance Substances 0.000 description 24
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
239000000203 mixture Substances 0.000 description 23
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 22
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 16
239000002585 base Substances 0.000 description 16
210000004027 cell Anatomy 0.000 description 16
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 16
239000011541 reaction mixture Substances 0.000 description 15
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 14
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 10
239000002775 capsule Substances 0.000 description 10
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 10
150000007530 organic bases Chemical class 0.000 description 10
239000003826 tablet Substances 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
102000001301 EGF receptor Human genes 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
239000002253 acid Substances 0.000 description 8
230000000694 effects Effects 0.000 description 8
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
238000003756 stirring Methods 0.000 description 8
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
108060006698 EGF receptor Proteins 0.000 description 7
102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 7
108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 7
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
239000000725 suspension Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
238000001816 cooling Methods 0.000 description 6
150000007529 inorganic bases Chemical class 0.000 description 6
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
239000007858 starting material Substances 0.000 description 6
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 6
YOETUEMZNOLGDB-UHFFFAOYSA-N 2-methylpropyl carbonochloridate Chemical compound CC(C)COC(Cl)=O YOETUEMZNOLGDB-UHFFFAOYSA-N 0.000 description 5
125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 5
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 5
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
239000012024 dehydrating agents‎ Substances 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
230000008020 evaporation Effects 0.000 description 5
239000005457 ice water Substances 0.000 description 5
239000002244 precipitate Substances 0.000 description 5
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 5
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 4
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
BMTAFVWTTFSTOG-UHFFFAOYSA-N Butylate Chemical compound CCSC(=O)N(CC(C)C)CC(C)C BMTAFVWTTFSTOG-UHFFFAOYSA-N 0.000 description 4
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
229960000583 acetic acid Drugs 0.000 description 4
239000012043 crude product Substances 0.000 description 4
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 4
210000001035 gastrointestinal tract Anatomy 0.000 description 4
230000002401 inhibitory effect Effects 0.000 description 4
239000008101 lactose Substances 0.000 description 4
235000019359 magnesium stearate Nutrition 0.000 description 4
OZUYHCUWZYGZMN-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-[4-(cyclopropylmethyl)piperazin-1-yl]but-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CC(OCC1CC1)=C2NC(=O)C=CCN1CCN(CC2CC2)CC1 OZUYHCUWZYGZMN-UHFFFAOYSA-N 0.000 description 4
FCLVDCYTWKKMSP-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CC(OCC1CC1)=C2NC(=O)C=CCN1CCCCC1 FCLVDCYTWKKMSP-UHFFFAOYSA-N 0.000 description 4
VEJULBFITNDVKI-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-pyrrolidin-1-ylbut-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CC(OCC1CC1)=C2NC(=O)C=CCN1CCCC1 VEJULBFITNDVKI-UHFFFAOYSA-N 0.000 description 4
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 4
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 4
239000001267 polyvinylpyrrolidone Substances 0.000 description 4
229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
229910052700 potassium Inorganic materials 0.000 description 4
239000011591 potassium Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
230000035755 proliferation Effects 0.000 description 4
230000009467 reduction Effects 0.000 description 4
238000006722 reduction reaction Methods 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
239000005051 trimethylchlorosilane Substances 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
IGWYUGYBENYOPE-UHFFFAOYSA-N 4-(4-acetylpiperazin-1-yl)-n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]but-2-enamide Chemical compound C1CN(C(=O)C)CCN1CC=CC(=O)NC(C(=CC1=NC=N2)OCC3CC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 IGWYUGYBENYOPE-UHFFFAOYSA-N 0.000 description 3
YMNYYZIVMKHWRG-UHFFFAOYSA-N 4-[4-[[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]amino]-4-oxobut-2-enyl]-n,n-dimethylpiperazine-1-carboxamide Chemical compound C1CN(C(=O)N(C)C)CCN1CC=CC(=O)NC(C(=CC1=NC=N2)OCC3CC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 YMNYYZIVMKHWRG-UHFFFAOYSA-N 0.000 description 3
KULGXJSSBLEZRX-UHFFFAOYSA-N 4-[bis(2-methoxyethyl)amino]-n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]but-2-enamide Chemical compound N1=CN=C2C=C(OCC3CC3)C(NC(=O)C=CCN(CCOC)CCOC)=CC2=C1NC1=CC=C(F)C(Cl)=C1 KULGXJSSBLEZRX-UHFFFAOYSA-N 0.000 description 3
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
102000009024 Epidermal Growth Factor Human genes 0.000 description 3
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
NQTADLQHYWFPDB-UHFFFAOYSA-N N-Hydroxysuccinimide Chemical compound ON1C(=O)CCC1=O NQTADLQHYWFPDB-UHFFFAOYSA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
101710098940 Pro-epidermal growth factor Proteins 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
150000007513 acids Chemical class 0.000 description 3
239000008346 aqueous phase Substances 0.000 description 3
ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 3
239000008120 corn starch Substances 0.000 description 3
239000007903 gelatin capsule Substances 0.000 description 3
239000003112 inhibitor Substances 0.000 description 3
230000001404 mediated effect Effects 0.000 description 3
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
230000019491 signal transduction Effects 0.000 description 3
235000009518 sodium iodide Nutrition 0.000 description 3
239000011975 tartaric acid Substances 0.000 description 3
235000002906 tartaric acid Nutrition 0.000 description 3
238000010626 work up procedure Methods 0.000 description 3
NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 2
BWYJJZBRYSADRP-UHFFFAOYSA-N 2-methoxyquinazoline Chemical compound C1=CC=CC2=NC(OC)=NC=C21 BWYJJZBRYSADRP-UHFFFAOYSA-N 0.000 description 2
XWNBDDPZLFKQCH-UHFFFAOYSA-N 4-n-(3-bromophenyl)-7-[3-(1-methylpiperidin-4-yl)propoxy]quinazoline-4,6-diamine Chemical compound C1CN(C)CCC1CCCOC1=CC2=NC=NC(NC=3C=C(Br)C=CC=3)=C2C=C1N XWNBDDPZLFKQCH-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
101000851176 Homo sapiens Pro-epidermal growth factor Proteins 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
108010002386 Interleukin-3 Proteins 0.000 description 2
102000000646 Interleukin-3 Human genes 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
101001033276 Mus musculus Interleukin-3 Proteins 0.000 description 2
HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
150000004703 alkoxides Chemical class 0.000 description 2
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 2
230000004071 biological effect Effects 0.000 description 2
238000009835 boiling Methods 0.000 description 2
206010006451 bronchitis Diseases 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
235000015165 citric acid Nutrition 0.000 description 2
239000002299 complementary DNA Substances 0.000 description 2
PAFZNILMFXTMIY-UHFFFAOYSA-N cyclohexylamine Chemical compound NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 2
230000001419 dependent effect Effects 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
239000012362 glacial acetic acid Substances 0.000 description 2
239000008187 granular material Substances 0.000 description 2
229940093915 gynecological organic acid Drugs 0.000 description 2
125000005843 halogen group Chemical group 0.000 description 2
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 2
239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
229940076264 interleukin-3 Drugs 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
239000012280 lithium aluminium hydride Substances 0.000 description 2
229910052943 magnesium sulfate Inorganic materials 0.000 description 2
235000019341 magnesium sulphate Nutrition 0.000 description 2
239000002609 medium Substances 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
TUDHHXITCLZTOH-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-(4-morpholin-4-ylpiperidin-1-yl)but-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CC(OCC1CC1)=C2NC(=O)C=CCN1CCC(N2CCOCC2)CC1 TUDHHXITCLZTOH-UHFFFAOYSA-N 0.000 description 2
KMAPIHHPUBUULD-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-[2-methoxyethyl(methyl)amino]but-2-enamide Chemical compound N1=CN=C2C=C(OCC3CC3)C(NC(=O)C=CCN(C)CCOC)=CC2=C1NC1=CC=C(F)C(Cl)=C1 KMAPIHHPUBUULD-UHFFFAOYSA-N 0.000 description 2
GSFRVLQEVPJFAS-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-[4-(oxolan-2-ylmethyl)piperazin-1-yl]but-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CC(OCC1CC1)=C2NC(=O)C=CCN1CCN(CC2OCCC2)CC1 GSFRVLQEVPJFAS-UHFFFAOYSA-N 0.000 description 2
ZGELLBSXYXUONO-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-[4-(oxolan-3-yl)piperazin-1-yl]but-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CC(OCC1CC1)=C2NC(=O)C=CCN1CCN(C2COCC2)CC1 ZGELLBSXYXUONO-UHFFFAOYSA-N 0.000 description 2
QKCRUVOKNLTSGH-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-cyclobutyloxyquinazolin-6-yl]-4-(2,5-dimethylpyrrolidin-1-yl)but-2-enamide Chemical compound CC1CCC(C)N1CC=CC(=O)NC(C(=CC1=NC=N2)OC3CCC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 QKCRUVOKNLTSGH-UHFFFAOYSA-N 0.000 description 2
GVUGOAYIVIDWIO-UFWWTJHBSA-N nepidermin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)CNC(=O)[C@@H](NC(=O)[C@@H](NC(=O)[C@H](CS)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@H](C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C(C)C)C(C)C)C1=CC=C(O)C=C1 GVUGOAYIVIDWIO-UFWWTJHBSA-N 0.000 description 2
150000002828 nitro derivatives Chemical class 0.000 description 2
GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
230000000144 pharmacologic effect Effects 0.000 description 2
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 2
125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000000843 powder Substances 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
150000003254 radicals Chemical class 0.000 description 2
230000028327 secretion Effects 0.000 description 2
238000000926 separation method Methods 0.000 description 2
230000008054 signal transmission Effects 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
239000012321 sodium triacetoxyborohydride Substances 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000600 sorbitol Substances 0.000 description 2
239000007921 spray Substances 0.000 description 2
230000000638 stimulation Effects 0.000 description 2
HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 2
239000000829 suppository Substances 0.000 description 2
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
125000001412 tetrahydropyranyl group Chemical group 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
230000007306 turnover Effects 0.000 description 2
229940075966 (+)- menthol Drugs 0.000 description 1
NOOLISFMXDJSKH-AEJSXWLSSA-N (+)-menthol Chemical compound CC(C)[C@H]1CC[C@H](C)C[C@@H]1O NOOLISFMXDJSKH-AEJSXWLSSA-N 0.000 description 1
QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
AAWZDTNXLSGCEK-LNVDRNJUSA-N (3r,5r)-1,3,4,5-tetrahydroxycyclohexane-1-carboxylic acid Chemical compound O[C@@H]1CC(O)(C(O)=O)C[C@@H](O)C1O AAWZDTNXLSGCEK-LNVDRNJUSA-N 0.000 description 1
125000006559 (C1-C3) alkylamino group Chemical group 0.000 description 1
125000006698 (C1-C3) dialkylamino group Chemical group 0.000 description 1
125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 1
MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 description 1
BIJHOXVSOJUIPD-UHFFFAOYSA-N 1-methoxy-n-methylpropan-2-amine Chemical compound CNC(C)COC BIJHOXVSOJUIPD-UHFFFAOYSA-N 0.000 description 1
CUZLJOLBIRPEFB-UHFFFAOYSA-N 1-methoxypropan-2-one Chemical compound COCC(C)=O CUZLJOLBIRPEFB-UHFFFAOYSA-N 0.000 description 1
LNSCNEJNLACZPA-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(2-methylphenyl)butanedioic acid Chemical compound CC1=CC=CC=C1C(O)(C(O)=O)C(O)(C(O)=O)C1=CC=CC=C1C LNSCNEJNLACZPA-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 1
ARJYMGOQJFRJEF-UHFFFAOYSA-N 2-methoxy-n-methylpropan-1-amine Chemical compound CNCC(C)OC ARJYMGOQJFRJEF-UHFFFAOYSA-N 0.000 description 1
NBEMORIANHKPTH-UHFFFAOYSA-N 2-methoxypropanoyl chloride Chemical compound COC(C)C(Cl)=O NBEMORIANHKPTH-UHFFFAOYSA-N 0.000 description 1
QYRYQOHCDCTGHJ-UHFFFAOYSA-N 3-(1-methylpiperidin-4-yl)propan-1-ol Chemical compound CN1CCC(CCCO)CC1 QYRYQOHCDCTGHJ-UHFFFAOYSA-N 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
DOTGZROJTAUYFQ-UHFFFAOYSA-N 4-bromobut-2-enoic acid Chemical compound OC(=O)C=CCBr DOTGZROJTAUYFQ-UHFFFAOYSA-N 0.000 description 1
UYQMNEZWVKRWMS-UHFFFAOYSA-N 4-chloro-7-fluoro-6-nitroquinazoline Chemical compound N1=CN=C2C=C(F)C([N+](=O)[O-])=CC2=C1Cl UYQMNEZWVKRWMS-UHFFFAOYSA-N 0.000 description 1
TXYBPUFOTLATPV-UHFFFAOYSA-N 4-n-(3-bromophenyl)-7-[2-(1-methylpiperidin-4-yl)ethoxy]quinazoline-4,6-diamine Chemical compound C1CN(C)CCC1CCOC1=CC2=NC=NC(NC=3C=C(Br)C=CC=3)=C2C=C1N TXYBPUFOTLATPV-UHFFFAOYSA-N 0.000 description 1
LKHNQAXOAXIXGM-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-7-(cyclopropylmethoxy)quinazoline-4,6-diamine Chemical compound N1=CN=C2C=C(OCC3CC3)C(N)=CC2=C1NC1=CC=C(F)C(Cl)=C1 LKHNQAXOAXIXGM-UHFFFAOYSA-N 0.000 description 1
NMYUQRVTMBHNKE-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-7-(oxolan-2-ylmethoxy)quinazoline-4,6-diamine Chemical compound N1=CN=C2C=C(OCC3OCCC3)C(N)=CC2=C1NC1=CC=C(F)C(Cl)=C1 NMYUQRVTMBHNKE-UHFFFAOYSA-N 0.000 description 1
WTUDZHNOOSLDHX-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-7-[3-(1-methylpiperidin-4-yl)propoxy]quinazoline-4,6-diamine Chemical compound C1CN(C)CCC1CCCOC1=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C2C=C1N WTUDZHNOOSLDHX-UHFFFAOYSA-N 0.000 description 1
BNFMXQNGNUVKID-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-7-[3-(4-methyl-1,4-diazepan-1-yl)propoxy]quinazoline-4,6-diamine Chemical compound C1CN(C)CCCN1CCCOC1=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C2C=C1N BNFMXQNGNUVKID-UHFFFAOYSA-N 0.000 description 1
WMEXYRJVTNKBNB-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)-7-cyclobutyloxyquinazoline-4,6-diamine Chemical compound N1=CN=C2C=C(OC3CCC3)C(N)=CC2=C1NC1=CC=C(F)C(Cl)=C1 WMEXYRJVTNKBNB-UHFFFAOYSA-N 0.000 description 1
PGHNDQKEEVRQBV-XESZBRCGSA-N 6-nitro-7-[2-(oxan-2-yloxy)ethoxy]-n-[(1r)-1-phenylethyl]quinazolin-4-amine Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C1=CC=2[N+]([O-])=O)=NC=NC1=CC=2OCCOC1CCCCO1 PGHNDQKEEVRQBV-XESZBRCGSA-N 0.000 description 1
IAILLDJQGVEDBR-UHFFFAOYSA-N 7-[3-(azetidin-1-yl)propoxy]-n-(3-chloro-4-fluorophenyl)-6-nitroquinazolin-4-amine Chemical compound N1=CN=C2C=C(OCCCN3CCC3)C([N+](=O)[O-])=CC2=C1NC1=CC=C(F)C(Cl)=C1 IAILLDJQGVEDBR-UHFFFAOYSA-N 0.000 description 1
RVDMWKXZEMDHKH-CYBMUJFWSA-N 7-cyclobutyloxy-4-n-[(1r)-1-phenylethyl]quinazoline-4,6-diamine Chemical compound N([C@H](C)C=1C=CC=CC=1)C(C1=CC=2N)=NC=NC1=CC=2OC1CCC1 RVDMWKXZEMDHKH-CYBMUJFWSA-N 0.000 description 1
208000003200 Adenoma Diseases 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
239000004475 Arginine Substances 0.000 description 1
108091003079 Bovine Serum Albumin Proteins 0.000 description 1
206010006458 Bronchitis chronic Diseases 0.000 description 1
229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
206010009900 Colitis ulcerative Diseases 0.000 description 1
AAWZDTNXLSGCEK-UHFFFAOYSA-N Cordycepinsaeure Natural products OC1CC(O)(C(O)=O)CC(O)C1O AAWZDTNXLSGCEK-UHFFFAOYSA-N 0.000 description 1
206010011224 Cough Diseases 0.000 description 1
208000011231 Crohn disease Diseases 0.000 description 1
CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
201000003883 Cystic fibrosis Diseases 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
206010014561 Emphysema Diseases 0.000 description 1
206010017807 Gastric mucosal hypertrophy Diseases 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
241000282412 Homo Species 0.000 description 1
102000014150 Interferons Human genes 0.000 description 1
108010050904 Interferons Proteins 0.000 description 1
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
239000012448 Lithium borohydride Substances 0.000 description 1
206010027476 Metastases Diseases 0.000 description 1
229920000168 Microcrystalline cellulose Polymers 0.000 description 1
208000034525 Ménétrier disease Diseases 0.000 description 1
206010029113 Neovascularisation Diseases 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
201000004681 Psoriasis Diseases 0.000 description 1
AAWZDTNXLSGCEK-ZHQZDSKASA-N Quinic acid Natural products O[C@H]1CC(O)(C(O)=O)C[C@H](O)C1O AAWZDTNXLSGCEK-ZHQZDSKASA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
206010039085 Rhinitis allergic Diseases 0.000 description 1
239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
102000006747 Transforming Growth Factor alpha Human genes 0.000 description 1
101800004564 Transforming growth factor alpha Proteins 0.000 description 1
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
208000025865 Ulcer Diseases 0.000 description 1
201000006704 Ulcerative Colitis Diseases 0.000 description 1
241000251539 Vertebrata <Metazoa> Species 0.000 description 1
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
CDFQPBHCLNAHJS-UHFFFAOYSA-N [N-]=[N+]=[N-].O=P(Oc1ccccc1)Oc1ccccc1 Chemical compound [N-]=[N+]=[N-].O=P(Oc1ccccc1)Oc1ccccc1 CDFQPBHCLNAHJS-UHFFFAOYSA-N 0.000 description 1
RSWGJHLUYNHPMX-ONCXSQPRSA-N abietic acid Chemical compound C([C@@H]12)CC(C(C)C)=CC1=CC[C@@H]1[C@]2(C)CCC[C@@]1(C)C(O)=O RSWGJHLUYNHPMX-ONCXSQPRSA-N 0.000 description 1
230000002159 abnormal effect Effects 0.000 description 1
230000007488 abnormal function Effects 0.000 description 1
IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 description 1
230000009471 action Effects 0.000 description 1
239000000654 additive Substances 0.000 description 1
229940009456 adriamycin Drugs 0.000 description 1
239000000443 aerosol Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910001508 alkali metal halide Inorganic materials 0.000 description 1
150000008045 alkali metal halides Chemical class 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
230000000172 allergic effect Effects 0.000 description 1
201000010105 allergic rhinitis Diseases 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
238000010640 amide synthesis reaction Methods 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000003110 anti-inflammatory effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
235000003704 aspartic acid Nutrition 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 description 1
235000013871 bee wax Nutrition 0.000 description 1
239000012166 beeswax Substances 0.000 description 1
229960000686 benzalkonium chloride Drugs 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
229940073608 benzyl chloride Drugs 0.000 description 1
CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
230000037396 body weight Effects 0.000 description 1
IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 1
RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
201000009267 bronchiectasis Diseases 0.000 description 1
229940124630 bronchodilator Drugs 0.000 description 1
230000001813 broncholytic effect Effects 0.000 description 1
HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
239000001506 calcium phosphate Substances 0.000 description 1
229910000389 calcium phosphate Inorganic materials 0.000 description 1
235000011010 calcium phosphates Nutrition 0.000 description 1
150000001728 carbonyl compounds Chemical class 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
239000008112 carboxymethyl-cellulose Substances 0.000 description 1
230000004663 cell proliferation Effects 0.000 description 1
238000001516 cell proliferation assay Methods 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
201000001352 cholecystitis Diseases 0.000 description 1
208000007451 chronic bronchitis Diseases 0.000 description 1
DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
229960004316 cisplatin Drugs 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
239000012228 culture supernatant Substances 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
229960004397 cyclophosphamide Drugs 0.000 description 1
230000007812 deficiency Effects 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
238000006471 dimerization reaction Methods 0.000 description 1
VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
239000012153 distilled water Substances 0.000 description 1
239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
230000008482 dysregulation Effects 0.000 description 1
BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
QJAFYVVTPMKFOX-UHFFFAOYSA-N ethyl 4-[[4-(3-bromoanilino)-7-[3-(1-methylpiperidin-4-yl)propoxy]quinazolin-6-yl]amino]-4-oxobut-2-enoate Chemical compound N1=CN=C2C=C(OCCCC3CCN(C)CC3)C(NC(=O)C=CC(=O)OCC)=CC2=C1NC1=CC=CC(Br)=C1 QJAFYVVTPMKFOX-UHFFFAOYSA-N 0.000 description 1
VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 description 1
229960005420 etoposide Drugs 0.000 description 1
239000012894 fetal calf serum Substances 0.000 description 1
238000011049 filling Methods 0.000 description 1
239000007941 film coated tablet Substances 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000008103 glucose Substances 0.000 description 1
235000001727 glucose Nutrition 0.000 description 1
239000004220 glutamic acid Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
229940116364 hard fat Drugs 0.000 description 1
210000003958 hematopoietic stem cell Anatomy 0.000 description 1
239000003667 hormone antagonist Substances 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
125000002349 hydroxyamino group Chemical group [H]ON([H])[*] 0.000 description 1
210000000987 immune system Anatomy 0.000 description 1
230000008595 infiltration Effects 0.000 description 1
238000001764 infiltration Methods 0.000 description 1
208000027866 inflammatory disease Diseases 0.000 description 1
230000002757 inflammatory effect Effects 0.000 description 1
230000004054 inflammatory process Effects 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
229940047124 interferons Drugs 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000004310 lactic acid Substances 0.000 description 1
235000014655 lactic acid Nutrition 0.000 description 1
229960004873 levomenthol Drugs 0.000 description 1
239000003446 ligand Substances 0.000 description 1
239000000314 lubricant Substances 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
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
229960002510 mandelic acid Drugs 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
230000009401 metastasis Effects 0.000 description 1
125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
230000011987 methylation Effects 0.000 description 1
238000007069 methylation reaction Methods 0.000 description 1
239000008108 microcrystalline cellulose Substances 0.000 description 1
235000019813 microcrystalline cellulose Nutrition 0.000 description 1
229940016286 microcrystalline cellulose Drugs 0.000 description 1
230000011278 mitosis Effects 0.000 description 1
230000004899 motility Effects 0.000 description 1
210000003097 mucus Anatomy 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
COKLBBUTGMUFNX-UHFFFAOYSA-N n-(3-bromophenyl)-7-[2-(1-methylpiperidin-4-yl)ethoxy]-6-nitroquinazolin-4-amine Chemical compound C1CN(C)CCC1CCOC1=CC2=NC=NC(NC=3C=C(Br)C=CC=3)=C2C=C1[N+]([O-])=O COKLBBUTGMUFNX-UHFFFAOYSA-N 0.000 description 1
SPRQBIBULHKTIB-UHFFFAOYSA-N n-(3-bromophenyl)-7-fluoro-6-nitroquinazolin-4-amine Chemical compound N1=CN=C2C=C(F)C([N+](=O)[O-])=CC2=C1NC1=CC=CC(Br)=C1 SPRQBIBULHKTIB-UHFFFAOYSA-N 0.000 description 1
FCXWQECJRGXOTR-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-nitro-7-(oxolan-2-ylmethoxy)quinazolin-4-amine Chemical compound N1=CN=C2C=C(OCC3OCCC3)C([N+](=O)[O-])=CC2=C1NC1=CC=C(F)C(Cl)=C1 FCXWQECJRGXOTR-UHFFFAOYSA-N 0.000 description 1
KFZCGTKDVDKFSQ-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-[3-(1-methylpiperidin-4-yl)propoxy]-6-nitroquinazolin-4-amine Chemical compound C1CN(C)CCC1CCCOC1=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C2C=C1[N+]([O-])=O KFZCGTKDVDKFSQ-UHFFFAOYSA-N 0.000 description 1
UXGLYQKCWSMNFX-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-[3-(4-methyl-1,4-diazepan-1-yl)propoxy]-6-nitroquinazolin-4-amine Chemical compound C1CN(C)CCCN1CCCOC1=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C2C=C1[N+]([O-])=O UXGLYQKCWSMNFX-UHFFFAOYSA-N 0.000 description 1
JPMFQRFIIPTVGV-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-7-cyclobutyloxy-6-nitroquinazolin-4-amine Chemical compound N1=CN=C2C=C(OC3CCC3)C([N+](=O)[O-])=CC2=C1NC1=CC=C(F)C(Cl)=C1 JPMFQRFIIPTVGV-UHFFFAOYSA-N 0.000 description 1
PXQVSAIVPDFYPR-UHFFFAOYSA-N n-[4-(3-bromoanilino)-7-(1-methylpiperidin-4-yl)oxyquinazolin-6-yl]but-2-enamide Chemical compound N1=CN=C2C=C(OC3CCN(C)CC3)C(NC(=O)C=CC)=CC2=C1NC1=CC=CC(Br)=C1 PXQVSAIVPDFYPR-UHFFFAOYSA-N 0.000 description 1
YCTRJRKKTDSOAW-UHFFFAOYSA-N n-[4-(3-bromoanilino)-7-(1-methylpiperidin-4-yl)oxyquinazolin-6-yl]prop-2-enamide Chemical compound C1CN(C)CCC1OC1=CC2=NC=NC(NC=3C=C(Br)C=CC=3)=C2C=C1NC(=O)C=C YCTRJRKKTDSOAW-UHFFFAOYSA-N 0.000 description 1
LHPBVOLVAGNTSZ-UHFFFAOYSA-N n-[4-(3-bromoanilino)-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-6-yl]prop-2-enamide Chemical compound C1CN(C)CCC1COC1=CC2=NC=NC(NC=3C=C(Br)C=CC=3)=C2C=C1NC(=O)C=C LHPBVOLVAGNTSZ-UHFFFAOYSA-N 0.000 description 1
QGFGHKHMKJCNNN-UHFFFAOYSA-N n-[4-(3-bromoanilino)-7-[2-(1-methylpiperidin-4-yl)ethoxy]quinazolin-6-yl]prop-2-enamide Chemical compound C1CN(C)CCC1CCOC1=CC2=NC=NC(NC=3C=C(Br)C=CC=3)=C2C=C1NC(=O)C=C QGFGHKHMKJCNNN-UHFFFAOYSA-N 0.000 description 1
GKXJYWDPHLJONY-UHFFFAOYSA-N n-[4-(3-bromoanilino)-7-[3-(1-methylpiperidin-4-yl)propoxy]quinazolin-6-yl]but-2-ynamide Chemical compound N1=CN=C2C=C(OCCCC3CCN(C)CC3)C(NC(=O)C#CC)=CC2=C1NC1=CC=CC(Br)=C1 GKXJYWDPHLJONY-UHFFFAOYSA-N 0.000 description 1
GTUKLOXJKHDUFQ-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-(2,6-dimethylmorpholin-4-yl)but-2-enamide Chemical compound C1C(C)OC(C)CN1CC=CC(=O)NC(C(=CC1=NC=N2)OCC3CC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 GTUKLOXJKHDUFQ-UHFFFAOYSA-N 0.000 description 1
YWRFCVANKUACCA-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-(2-methylpiperidin-1-yl)but-2-enamide Chemical compound CC1CCCCN1CC=CC(=O)NC(C(=CC1=NC=N2)OCC3CC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 YWRFCVANKUACCA-UHFFFAOYSA-N 0.000 description 1
HWANADBFRKAPGQ-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-(2-methylpyrrolidin-1-yl)but-2-enamide Chemical compound CC1CCCN1CC=CC(=O)NC(C(=CC1=NC=N2)OCC3CC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 HWANADBFRKAPGQ-UHFFFAOYSA-N 0.000 description 1
QLUFOFJVUMOBGO-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-(4-ethylpiperazin-1-yl)but-2-enamide Chemical compound C1CN(CC)CCN1CC=CC(=O)NC(C(=CC1=NC=N2)OCC3CC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 QLUFOFJVUMOBGO-UHFFFAOYSA-N 0.000 description 1
BHEXDWNZKZGCJR-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-(dimethylamino)but-2-enamide Chemical compound N1=CN=C2C=C(OCC3CC3)C(NC(=O)C=CCN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 BHEXDWNZKZGCJR-UHFFFAOYSA-N 0.000 description 1
NIENRZHBXLVTIC-FQEVSTJZSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-[(2s)-2-(methoxymethyl)pyrrolidin-1-yl]but-2-enamide Chemical compound COC[C@@H]1CCCN1CC=CC(=O)NC(C(=CC1=NC=N2)OCC3CC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 NIENRZHBXLVTIC-FQEVSTJZSA-N 0.000 description 1
QXJXSRHEHYAXFI-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-[2-methoxypropyl(methyl)amino]but-2-enamide Chemical compound N1=CN=C2C=C(OCC3CC3)C(NC(=O)C=CCN(C)CC(C)OC)=CC2=C1NC1=CC=C(F)C(Cl)=C1 QXJXSRHEHYAXFI-UHFFFAOYSA-N 0.000 description 1
LBPDPEBIWIMDTG-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-[3-methoxypropyl(methyl)amino]but-2-enamide Chemical compound N1=CN=C2C=C(OCC3CC3)C(NC(=O)C=CCN(C)CCCOC)=CC2=C1NC1=CC=C(F)C(Cl)=C1 LBPDPEBIWIMDTG-UHFFFAOYSA-N 0.000 description 1
KBLVCRCTZMPZMN-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-[4-(diethylaminomethyl)piperidin-1-yl]but-2-enamide Chemical compound C1CC(CN(CC)CC)CCN1CC=CC(=O)NC(C(=CC1=NC=N2)OCC3CC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 KBLVCRCTZMPZMN-UHFFFAOYSA-N 0.000 description 1
RZXDHUMXDRFOBK-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-[methyl-(1-methylpiperidin-4-yl)amino]but-2-enamide Chemical compound C1CN(C)CCC1N(C)CC=CC(=O)NC(C(=CC1=NC=N2)OCC3CC3)=CC1=C2NC1=CC=C(F)C(Cl)=C1 RZXDHUMXDRFOBK-UHFFFAOYSA-N 0.000 description 1
PQTDSJWQNYBZMA-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-(cyclopropylmethoxy)quinazolin-6-yl]-4-morpholin-4-ylbut-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CC(OCC1CC1)=C2NC(=O)C=CCN1CCOCC1 PQTDSJWQNYBZMA-UHFFFAOYSA-N 0.000 description 1
KDYYMULJAVESKY-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-[3-(4-methyl-1,4-diazepan-1-yl)propoxy]quinazolin-6-yl]prop-2-enamide Chemical compound C1CN(C)CCCN1CCCOC1=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C2C=C1NC(=O)C=C KDYYMULJAVESKY-UHFFFAOYSA-N 0.000 description 1
LFGWXNIIQPTINQ-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-cyclobutyloxyquinazolin-6-yl]-4-(diethylamino)but-2-enamide Chemical compound N1=CN=C2C=C(OC3CCC3)C(NC(=O)C=CCN(CC)CC)=CC2=C1NC1=CC=C(F)C(Cl)=C1 LFGWXNIIQPTINQ-UHFFFAOYSA-N 0.000 description 1
YZPACYGAVMMGRL-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-cyclobutyloxyquinazolin-6-yl]-4-morpholin-4-ylbut-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CC(OC1CCC1)=C2NC(=O)C=CCN1CCOCC1 YZPACYGAVMMGRL-UHFFFAOYSA-N 0.000 description 1
ZAVHCRUTUZHLEM-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)-7-cyclobutyloxyquinazolin-6-yl]-4-piperidin-1-ylbut-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CC(OC1CCC1)=C2NC(=O)C=CCN1CCCCC1 ZAVHCRUTUZHLEM-UHFFFAOYSA-N 0.000 description 1
WUGJVOQYSOSMOU-UHFFFAOYSA-N n-[7-[3-(azetidin-1-yl)propoxy]-4-(3-chloro-4-fluoroanilino)quinazolin-6-yl]prop-2-enamide Chemical compound C1=C(Cl)C(F)=CC=C1NC1=NC=NC2=CC(OCCCN3CCC3)=C(NC(=O)C=C)C=C12 WUGJVOQYSOSMOU-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
LQVZUXUQGFIYEK-UHFFFAOYSA-N n-methyloxolan-3-amine Chemical compound CNC1CCOC1 LQVZUXUQGFIYEK-UHFFFAOYSA-N 0.000 description 1
208000037916 non-allergic rhinitis Diseases 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
BOTREHHXSQGWTR-UHFFFAOYSA-N oxolane-3-carboxylic acid Chemical compound OC(=O)C1CCOC1 BOTREHHXSQGWTR-UHFFFAOYSA-N 0.000 description 1
238000004806 packaging method and process Methods 0.000 description 1
230000035778 pathophysiological process Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 1
239000006187 pill Substances 0.000 description 1
125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
150000003141 primary amines Chemical class 0.000 description 1
239000000047 product Substances 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
208000005069 pulmonary fibrosis Diseases 0.000 description 1
238000000746 purification Methods 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
208000023504 respiratory system disease Diseases 0.000 description 1
230000001177 retroviral effect Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
238000009097 single-agent therapy Methods 0.000 description 1
201000009890 sinusitis Diseases 0.000 description 1
239000001632 sodium acetate Substances 0.000 description 1
235000017281 sodium acetate Nutrition 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
208000011580 syndromic disease Diseases 0.000 description 1
229960001603 tamoxifen 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
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000004192 tetrahydrofuran-2-yl group Chemical group [H]C1([H])OC([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
229940044693 topoisomerase inhibitor Drugs 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000002753 trypsin inhibitor Substances 0.000 description 1
230000001173 tumoral effect Effects 0.000 description 1
231100000397 ulcer Toxicity 0.000 description 1
241001430294 unidentified retrovirus Species 0.000 description 1
HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
210000003556 vascular endothelial cell Anatomy 0.000 description 1
229960003048 vinblastine Drugs 0.000 description 1
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
- 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
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- 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
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Gastroenterology & Hepatology (AREA)
Pulmonology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

NO20016185A 1999-06-21 2001-12-18 Bicykliske heterocykler, medikamenter inneholdende disse forbindelser, deres anvendelse og fremgangsmate for fremstilling av dem. NO322094B1 (no)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
DE1999128281 DE19928281A1 (de)	1999-06-21	1999-06-21	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
US14664499P	1999-07-30	1999-07-30
DE2000123085 DE10023085A1 (de)	2000-05-11	2000-05-11	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
PCT/EP2000/005547 WO2000078735A1 (de)	1999-06-21	2000-06-16	Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung

Publications (3)

Publication Number	Publication Date
NO20016185D0 NO20016185D0 (no)	2001-12-18
NO20016185L NO20016185L (no)	2001-12-18
NO322094B1 true NO322094B1 (no)	2006-08-14

Family

ID=27213849

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20016185A NO322094B1 (no)	1999-06-21	2001-12-18	Bicykliske heterocykler, medikamenter inneholdende disse forbindelser, deres anvendelse og fremgangsmate for fremstilling av dem.

Country Status (26)

Country	Link
US (4)	US7220750B2 (pt)
EP (2)	EP1194418A1 (pt)
JP (1)	JP3686610B2 (pt)
KR (1)	KR100709909B1 (pt)
CN (1)	CN1166645C (pt)
AU (1)	AU775285B2 (pt)
BG (1)	BG65890B1 (pt)
CA (1)	CA2375259C (pt)
CZ (1)	CZ302365B6 (pt)
DK (1)	DK1731511T3 (pt)
EA (1)	EA004981B1 (pt)
EE (1)	EE04748B1 (pt)
ES (1)	ES2552813T3 (pt)
HK (1)	HK1044769B (pt)
HU (1)	HUP0201900A3 (pt)
IL (2)	IL147133A0 (pt)
ME (1)	MEP45508A (pt)
MX (1)	MXPA01012899A (pt)
NO (1)	NO322094B1 (pt)
NZ (1)	NZ516633A (pt)
PT (1)	PT1731511E (pt)
SK (1)	SK287010B6 (pt)
TR (1)	TR200103692T2 (pt)
UA (1)	UA71976C2 (pt)
WO (1)	WO2000078735A1 (pt)
YU (1)	YU90901A (pt)

Families Citing this family (101)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
MXPA01012899A (es) *	1999-06-21	2002-07-30	Boehringer Ingelheim Pharma	Heterociclos biciclicos, medicamentos que contienen estos compuestos, su empleo y procedimientos para su preparacion.
DE10042060A1 (de) *	2000-08-26	2002-03-07	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
US7776315B2 (en) *	2000-10-31	2010-08-17	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Pharmaceutical compositions based on anticholinergics and additional active ingredients
US20030158196A1 (en) *	2002-02-16	2003-08-21	Boehringer Ingelheim Pharma Gmbh Co. Kg	Pharmaceutical compositions based on anticholinergics and EGFR kinase inhibitors
US20100310477A1 (en) *	2000-11-28	2010-12-09	Boehringer Ingelheim Pharma Gmbh & Co. Kg.	Pharmaceutical compositions based on anticholingerics and additional active ingredients
US7019012B2 (en)	2000-12-20	2006-03-28	Boehringer Ingelheim International Pharma Gmbh & Co. Kg	Quinazoline derivatives and pharmaceutical compositions containing them
DE10063435A1 (de) *	2000-12-20	2002-07-04	Boehringer Ingelheim Pharma	Chinazolinderviate,diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
NZ528216A (en) *	2001-02-24	2006-12-22	Boehringer Ingelheim Pharma	Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
US6706699B2 (en)	2001-06-21	2004-03-16	Ariad Pharmaceuticals, Inc.	Quinolines and uses thereof
DE10204462A1 (de) *	2002-02-05	2003-08-07	Boehringer Ingelheim Pharma	Verwendung von Tyrosinkinase-Inhibitoren zur Behandlung inflammatorischer Prozesse
TW200813014A (en)	2002-03-28	2008-03-16	Astrazeneca Ab	Quinazoline derivatives
US6924285B2 (en)	2002-03-30	2005-08-02	Boehringer Ingelheim Pharma Gmbh & Co.	Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them
DE10217689A1 (de) *	2002-04-19	2003-11-13	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, ihre Verwendung und Verfahren zu ihrer Herstellung
US20040044014A1 (en)	2002-04-19	2004-03-04	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof
DE10221018A1 (de)	2002-05-11	2003-11-27	Boehringer Ingelheim Pharma	Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie
DE10230751A1 (de) *	2002-07-09	2004-01-22	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Neue Arzneimittelkompositionen auf der Basis neuer Anticholinergika und EGFR-Kinase-Hemmern
US20040048887A1 (en) *	2002-07-09	2004-03-11	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Pharmaceutical compositions based on anticholinergics and EGFR kinase inhibitors
JP4703183B2 (ja)	2002-07-15	2011-06-15	シンフォニーエボルーション，インク．	受容体型キナーゼモジュレーターおよびその使用方法
US7407955B2 (en) *	2002-08-21	2008-08-05	Boehringer Ingelheim Pharma Gmbh & Co., Kg	8-[3-amino-piperidin-1-yl]-xanthines, the preparation thereof and their use as pharmaceutical compositions
US7495005B2 (en) *	2002-08-22	2009-02-24	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Xanthine derivatives, their preparation and their use in pharmaceutical compositions
US7482337B2 (en)	2002-11-08	2009-01-27	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Xanthine derivatives, the preparation thereof and their use as pharmaceutical compositions
DE10254304A1 (de) *	2002-11-21	2004-06-03	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Neue Xanthinderivate, deren Herstellung und deren Verwendung als Arzneimittel
US7223749B2 (en) *	2003-02-20	2007-05-29	Boehringer Ingelheim International Gmbh	Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them
US20050043233A1 (en) *	2003-04-29	2005-02-24	Boehringer Ingelheim International Gmbh	Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis
US7566707B2 (en) *	2003-06-18	2009-07-28	Boehringer Ingelheim International Gmbh	Imidazopyridazinone and imidazopyridone derivatives, the preparation thereof and their use as pharmaceutical compositions
US8309562B2 (en)	2003-07-03	2012-11-13	Myrexis, Inc.	Compounds and therapeutical use thereof
GB0317665D0 (en)	2003-07-29	2003-09-03	Astrazeneca Ab	Qinazoline derivatives
EP1660479A1 (en) *	2003-07-29	2006-05-31	Astrazeneca AB	Piperidyl-quinazoline derivatives as tyrosine kinase inhibitors
CA2538884C (en) *	2003-09-16	2010-09-21	Astrazeneca Ab	Quinazoline derivatives as tyrosine kinase inhibitors
WO2005026156A1 (en) *	2003-09-16	2005-03-24	Astrazeneca Ab	Quinazoline derivatives
CN1882569B (zh)	2003-09-19	2010-09-29	阿斯利康(瑞典)有限公司	喹唑啉衍生物
US20070037837A1 (en) *	2003-09-19	2007-02-15	Hennequin Laurent Francois A	Quinazoline derivatives
AU2004276055A1 (en) *	2003-09-25	2005-04-07	Astrazeneca Ab	Quinazoline derivatives
ES2651730T3 (es) *	2003-09-26	2018-01-29	Exelixis, Inc.	Moduladores c-Met y métodos de uso
US7456189B2 (en)	2003-09-30	2008-11-25	Boehringer Ingelheim International Gmbh	Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation
DE10345875A1 (de) *	2003-09-30	2005-04-21	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Vewendung und Verfahren zu ihrer Herstellung
DE10349113A1 (de)	2003-10-17	2005-05-12	Boehringer Ingelheim Pharma	Verfahren zur Herstellung von Aminocrotonylverbindungen
DE10355304A1 (de)	2003-11-27	2005-06-23	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Neue 8-(Piperazin-1-yl)-und 8-([1,4]Diazepan-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
US20050203088A1 (en) *	2004-01-09	2005-09-15	Boehringer Ingelheim International Gmbh	Medicament combinations based on scopine- or tropene acid esters with EGFR-kinase inhibitors
US7632840B2 (en)	2004-02-03	2009-12-15	Astrazeneca Ab	Quinazoline compounds for the treatment of hyperproliferative disorders
US7501426B2 (en) *	2004-02-18	2009-03-10	Boehringer Ingelheim International Gmbh	8-[3-amino-piperidin-1-yl]-xanthines, their preparation and their use as pharmaceutical compositions
DE102004009039A1 (de) *	2004-02-23	2005-09-08	Boehringer Ingelheim Pharma Gmbh & Co. Kg	8-[3-Amino-piperidin-1-yl]-xanthine, deren Herstellung und Verwendung als Arzneimittel
US7179809B2 (en) *	2004-04-10	2007-02-20	Boehringer Ingelheim International Gmbh	2-Amino-imidazo[4,5-d]pyridazin-4-ones, their preparation and their use as pharmaceutical compositions
DK1746999T3 (da)	2004-05-06	2012-01-23	Warner Lambert Co	4-phenylamino-quinazolin-6-yl-amider
US7439370B2 (en)	2004-05-10	2008-10-21	Boehringer Ingelheim International Gmbh	Imidazole derivatives, their preparation and their use as intermediates for the preparation of pharmaceutical compositions and pesticides
DE102004030502A1 (de) *	2004-06-24	2006-01-12	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Neue Imidazole und Triazole, deren Herstellung und Verwendung als Arzneimittel
US20060035893A1 (en)	2004-08-07	2006-02-16	Boehringer Ingelheim International Gmbh	Pharmaceutical compositions for treatment of respiratory and gastrointestinal disorders
DE102004043944A1 (de) *	2004-09-11	2006-03-30	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Neue 8-(3-Amino-piperidin-1-yl)-7-(but-2-inyl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
DE102004044221A1 (de) *	2004-09-14	2006-03-16	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Neue 3-Methyl-7-butinyl-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
DE102004054054A1 (de) *	2004-11-05	2006-05-11	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Verfahren zur Herstellung chiraler 8-(3-Amino-piperidin-1-yl)-xanthine
PE20060777A1 (es)	2004-12-24	2006-10-06	Boehringer Ingelheim Int	Derivados de indolinona para el tratamiento o la prevencion de enfermedades fibroticas
CA2592900A1 (en)	2005-01-03	2006-07-13	Myriad Genetics Inc.	Nitrogen containing bicyclic compounds and therapeutical use thereof
US8258145B2 (en)	2005-01-03	2012-09-04	Myrexis, Inc.	Method of treating brain cancer
WO2006081741A1 (fr) *	2005-02-05	2006-08-10	Piaoyang Sun	Dérivés de quinazoline ou leurs sels de qualité pharmaceutique, synthèse et applications médicales desdites substances
CA2599210A1 (en)	2005-02-26	2006-08-31	Astrazeneca Ab	Quinazoline derivatives as tyrosine kinase inhibitors
DE102005035891A1 (de)	2005-07-30	2007-02-08	Boehringer Ingelheim Pharma Gmbh & Co. Kg	8-(3-Amino-piperidin-1-yl)-xanthine, deren Herstellung und deren Verwendung als Arzneimittel
KR100832594B1 (ko) *	2005-11-08	2008-05-27	한미약품 주식회사	다중저해제로서의 퀴나졸린 유도체 및 이의 제조방법
SI1948180T1 (sl) *	2005-11-11	2013-06-28	Boehringer Ingelheim International Gmbh	Kombinacijsko zdravljenje raka, ki obsega EGFR/HER2 inhibitorje
JP5688877B2 (ja)	2005-11-11	2015-03-25	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	癌疾患の治療用キナゾリン誘導体
US7960546B2 (en)	2006-01-26	2011-06-14	Boehringer Ingelheim International Gmbh	Process for preparing aminocrotonylamino-substituted quinazoline derivatives
EP1852108A1 (en) *	2006-05-04	2007-11-07	Boehringer Ingelheim Pharma GmbH & Co.KG	DPP IV inhibitor formulations
NO347644B1 (no)	2006-05-04	2024-02-12	Boehringer Ingelheim Int	Polymorfer
PE20110235A1 (es) *	2006-05-04	2011-04-14	Boehringer Ingelheim Int	Combinaciones farmaceuticas que comprenden linagliptina y metmorfina
JP2010500326A (ja)	2006-08-08	2010-01-07	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	糖尿病の治療のためのｄｐｐ−ｉｖ阻害剤としてのピロロ［３，２−ｄ］ピリミジン
ATE552835T1 (de)	2006-09-18	2012-04-15	Boehringer Ingelheim Int	Verfahren zur behandlung von tumoren mit egfr- mutationen
EP1921070A1 (de)	2006-11-10	2008-05-14	Boehringer Ingelheim Pharma GmbH & Co. KG	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstelllung
KR20090116782A (ko)	2007-02-06	2009-11-11	베링거 인겔하임 인터내셔날 게엠베하	바이사이클릭 헤테로사이클, 당해 화합물을 함유하는 약물, 이의 용도 및 이의 제조방법
RS52573B (en)	2008-02-07	2013-04-30	Boehringer Ingelheim International Gmbh	SPIROCYCLIC HETEROCYCLES, THE MEDICINAL PRODUCTS CONTAINING THIS UNIT, THEIR APPLICATION AND THE PROCEDURE FOR THEIR MANUFACTURING
PE20091730A1 (es)	2008-04-03	2009-12-10	Boehringer Ingelheim Int	Formulaciones que comprenden un inhibidor de dpp4
WO2009138781A1 (en)	2008-05-13	2009-11-19	Astrazeneca Ab	Fumarate salt of 4- (3-chloro-2-fluoroanilino) -7-methoxy-6- { [1- (n-methylcarbamoylmethyl) piperidin- 4-yl] oxy}quinazoline
UY31867A (es)	2008-06-06	2010-01-29	Boehringer Ingelheim Int	Nuevas formulaciones farmacéuticas sólidas que comprenden bibw 2992
KR20200118243A (ko)	2008-08-06	2020-10-14	베링거 인겔하임 인터내셔날 게엠베하	메트포르민 요법이 부적합한 환자에서의 당뇨병 치료
UY32030A (es)	2008-08-06	2010-03-26	Boehringer Ingelheim Int	"tratamiento para diabetes en pacientes inapropiados para terapia con metformina"
EP2313397B1 (de)	2008-08-08	2016-04-20	Boehringer Ingelheim International GmbH	Cyclohexyloxy-substituierte heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung
KR20110067096A (ko)	2008-09-10	2011-06-21	베링거 인겔하임 인터내셔날 게엠베하	당뇨병 및 관련 상태를 치료하기 위한 병용 요법
US20200155558A1 (en)	2018-11-20	2020-05-21	Boehringer Ingelheim International Gmbh	Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug
KR101703941B1 (ko)	2008-11-10	2017-02-07	내셔날 헬스 리서치 인스티튜트	티로신 키나아제 억제제로서의 접합 이환 및 삼환 피리미딘 화합물
NZ592924A (en)	2008-12-23	2014-05-30	Boehringer Ingelheim Int	Salt forms of a xanthine derivative
AR074990A1 (es)	2009-01-07	2011-03-02	Boehringer Ingelheim Int	Tratamiento de diabetes en pacientes con un control glucemico inadecuado a pesar de la terapia con metformina
CN102388024A (zh)	2009-01-16	2012-03-21	埃克塞里艾克西斯公司	N-(4-{[6,7-双(甲基氧基)喹啉-4-基]氧基}苯基)-n’-(4-氟苯基)环丙烷-1,1-二甲酰胺的苹果酸盐及其用于癌症治疗的结晶型
DK2451445T3 (da)	2009-07-06	2019-06-24	Boehringer Ingelheim Int	Fremgangsmåde til at tørre bibw2992, dets salte og faste farmaceutiske formuleringer omfattende denne aktive ingrediens
UA108618C2 (uk)	2009-08-07	2015-05-25		Застосування c-met-модуляторів в комбінації з темозоломідом та/або променевою терапією для лікування раку
EA034869B1 (ru)	2009-11-27	2020-03-31	Бёрингер Ингельхайм Интернациональ Гмбх	Лечение генотипированных пациентов с диабетом ингибиторами дпп-4, такими как линаглиптин
WO2011138421A1 (en)	2010-05-05	2011-11-10	Boehringer Ingelheim International Gmbh	Combination therapy
KR20130093012A (ko)	2010-06-24	2013-08-21	베링거 인겔하임 인터내셔날 게엠베하	당뇨병 요법
US9034883B2 (en)	2010-11-15	2015-05-19	Boehringer Ingelheim International Gmbh	Vasoprotective and cardioprotective antidiabetic therapy
US8828391B2 (en)	2011-05-17	2014-09-09	Boehringer Ingelheim International Gmbh	Method for EGFR directed combination treatment of non-small cell lung cancer
EP3517539B1 (en)	2011-07-15	2022-12-14	Boehringer Ingelheim International GmbH	Substituted dimeric quinazoline derivative, its preparation and its use in pharmaceutical compositions for the treatment of type i and ii diabetes
US9555001B2 (en)	2012-03-07	2017-01-31	Boehringer Ingelheim International Gmbh	Pharmaceutical composition and uses thereof
JP6224084B2 (ja)	2012-05-14	2017-11-01	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	糸球体上皮細胞関連障害及び／又はネフローゼ症候群の治療に用いるｄｐｐ−４阻害薬としてのキサンチン誘導体
WO2013174767A1 (en)	2012-05-24	2013-11-28	Boehringer Ingelheim International Gmbh	A xanthine derivative as dpp -4 inhibitor for use in modifying food intake and regulating food preference
EP2875020B1 (en)	2012-07-19	2017-09-06	Boehringer Ingelheim International GmbH	Process for the preparation of a fumaric acid salt of 9-[4-(3-chloro-2-fluoro-phenylamino)-7-methoxy- chinazolin-6-yloxy]-1,4-diaza-spiro[5.5]undecan-5-one
CN103804308A (zh) *	2012-11-06	2014-05-21	天津药物研究院	7-取代环己基喹唑啉衍生物及其制备方法和用途
CN103965175B (zh) *	2013-02-05	2017-12-22	齐鲁制药有限公司	4‑(取代苯氨基)喹唑啉类化合物、其制备方法及应用
WO2014177038A1 (en)	2013-04-28	2014-11-06	Sunshine Lake Pharma Co., Ltd.	Aminoquinazoline derivatives and their salts and methods of use thereof
US9242965B2 (en)	2013-12-31	2016-01-26	Boehringer Ingelheim International Gmbh	Process for the manufacture of (E)-4-N,N-dialkylamino crotonic acid in HX salt form and use thereof for synthesis of EGFR tyrosine kinase inhibitors
JP6615109B2 (ja)	2014-02-28	2019-12-04	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	Ｄｐｐ−４阻害薬の医学的使用
WO2017141271A1 (en) *	2016-02-17	2017-08-24	Sun Pharmaceutical Industries Ltd.	Stable pharmaceutical composition of afatinib
EP4233840A3 (en)	2016-06-10	2023-10-18	Boehringer Ingelheim International GmbH	Combinations of linagliptin and metformin
BR112021005513A2 (pt)	2018-09-25	2021-06-22	Black Diamond Therapeutics, Inc.	derivados de quinazolina como inibidor de tirosina quinase, composições, métodos de fabricação e uso dos mesmos
CN109096208B (zh) *	2018-10-10	2021-11-19	中国科学院上海有机化学研究所	一种喹唑啉衍生物及其制备方法和应用

Family Cites Families (66)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9300059D0 (en) *	1992-01-20	1993-03-03	Zeneca Ltd	Quinazoline derivatives
GB9401182D0 (en)	1994-01-21	1994-03-16	Inst Of Cancer The Research	Antibodies to EGF receptor and their antitumour effect
DK0817775T3 (da)	1995-03-30	2001-11-19	Pfizer	Quinazolinderivater
GB9508538D0 (en)	1995-04-27	1995-06-14	Zeneca Ltd	Quinazoline derivatives
EA001428B1 (ru)	1995-07-06	2001-02-26	Новартис Аг	Пирролопиримидины и фармацевтические композиции, включающие эти соединения
GB9624482D0 (en) *	1995-12-18	1997-01-15	Zeneca Phaema S A	Chemical compounds
GB9603095D0 (en) *	1996-02-14	1996-04-10	Zeneca Ltd	Quinazoline derivatives
IL120302A0 (en)	1996-03-27	1997-06-10	Pfizer	Use of alpha1-adrenoreceptor antagonists in the prevention and treatment of benign prostatic hyperplasia
BR9708640B1 (pt) *	1996-04-12	2013-06-11		inibidores irreversÍveis de tirosina-cinases e composiÇço farmacÊutica compreendendo os mesmo.
GB9718972D0 (en) *	1996-09-25	1997-11-12	Zeneca Ltd	Chemical compounds
UA73073C2 (uk) *	1997-04-03	2005-06-15	Уайт Холдінгз Корпорейшн	Заміщені 3-ціанохіноліни, спосіб їх одержання та фармацевтична композиція
ZA986732B (en) *	1997-07-29	1999-02-02	Warner Lambert Co	Irreversible inhibitiors of tyrosine kinases
ZA986729B (en) *	1997-07-29	1999-02-02	Warner Lambert Co	Irreversible inhibitors of tyrosine kinases
TW436485B (en) *	1997-08-01	2001-05-28	American Cyanamid Co	Substituted quinazoline derivatives
US6251912B1 (en) *	1997-08-01	2001-06-26	American Cyanamid Company	Substituted quinazoline derivatives
RS49779B (sr)	1998-01-12	2008-06-05	Glaxo Group Limited,	Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze
US6297258B1 (en) *	1998-09-29	2001-10-02	American Cyanamid Company	Substituted 3-cyanoquinolines
US6262088B1 (en)	1998-11-19	2001-07-17	Berlex Laboratories, Inc.	Polyhydroxylated monocyclic N-heterocyclic derivatives as anti-coagulants
DE19911366A1 (de)	1999-03-15	2000-09-21	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
NZ513802A (en) *	1999-02-27	2001-09-28	Boehringer Ingelheim Pharma	4-amino-quinazoline and quinoline derivatives having an inhibitory effect on signal transduction mediated by tyrosine kinases
DE19911509A1 (de)	1999-03-15	2000-09-21	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
MXPA01012899A (es) *	1999-06-21	2002-07-30	Boehringer Ingelheim Pharma	Heterociclos biciclicos, medicamentos que contienen estos compuestos, su empleo y procedimientos para su preparacion.
US20060063752A1 (en) *	2000-03-14	2006-03-23	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them
BR0109828A (pt) *	2000-04-07	2002-12-17	Astrazeneca Ab	Composto, processo para a prepapação do mesmo ou de um sal deste, composição farmacêutica, uso do composto ou de um sal deste farmaceuticamente aceitável, e, método para a produção de um efeito antiangiogênico e/ou redutor da permeabilidade vascular em um animal de sangue quente em necessidade de tal tratamento
EP1280798B1 (de)	2000-04-08	2007-01-03	Boehringer Ingelheim Pharma GmbH & Co.KG	Bicyclische heterocyclen, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung
US6627634B2 (en) *	2000-04-08	2003-09-30	Boehringer Ingelheim Pharma Kg	Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them
EP1295872A4 (en) *	2000-06-02	2007-05-16	Shionogi & Co	ANTAGONIST MEDICINAL PRODUCT FOR PGD2 / TXA2 RECEPTORS
DE10042060A1 (de)	2000-08-26	2002-03-07	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
US6653305B2 (en) *	2000-08-26	2003-11-25	Boehringer Ingelheim Pharma Kg	Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them
US6656946B2 (en) *	2000-08-26	2003-12-02	Boehringer Ingelheim Pharma Kg	Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases
US6617329B2 (en) *	2000-08-26	2003-09-09	Boehringer Ingelheim Pharma Kg	Aminoquinazolines and their use as medicaments
DE10042059A1 (de)	2000-08-26	2002-03-07	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
DE10042058A1 (de)	2000-08-26	2002-03-07	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
DE10042062A1 (de)	2000-08-26	2002-03-07	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Hertellung
DE10042064A1 (de)	2000-08-26	2002-03-07	Boehringer Ingelheim Pharma	Chinazoline, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
US20020082270A1 (en) *	2000-08-26	2002-06-27	Frank Himmelsbach	Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases
US6740651B2 (en) *	2000-08-26	2004-05-25	Boehringer Ingelheim Pharma Kg	Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases
US6403580B1 (en) *	2000-08-26	2002-06-11	Boehringer Ingelheim Pharma Kg	Quinazolines, pharmaceutical compositions containing these compounds, their use and processes for preparing them
ATE369894T1 (de)	2000-11-22	2007-09-15	Novartis Pharma Gmbh	Kombination enthaltend ein mittel zur verminderung von vegf-aktivität und ein mittel zur verminderung von egf-aktivität
US7019012B2 (en) *	2000-12-20	2006-03-28	Boehringer Ingelheim International Pharma Gmbh & Co. Kg	Quinazoline derivatives and pharmaceutical compositions containing them
DE10063435A1 (de)	2000-12-20	2002-07-04	Boehringer Ingelheim Pharma	Chinazolinderviate,diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
DE10204462A1 (de) *	2002-02-05	2003-08-07	Boehringer Ingelheim Pharma	Verwendung von Tyrosinkinase-Inhibitoren zur Behandlung inflammatorischer Prozesse
TW200813014A (en) *	2002-03-28	2008-03-16	Astrazeneca Ab	Quinazoline derivatives
NZ536114A (en)	2002-03-30	2007-11-30	Boehringer Ingelheim Pharma	4-(N-phenylamino)-quinazolines / quinolines as tyrosine kinase inhibitors
US6924285B2 (en) *	2002-03-30	2005-08-02	Boehringer Ingelheim Pharma Gmbh & Co.	Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them
DE10217689A1 (de)	2002-04-19	2003-11-13	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, ihre Verwendung und Verfahren zu ihrer Herstellung
US20040044014A1 (en) *	2002-04-19	2004-03-04	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for the preparation thereof
US20030225079A1 (en) *	2002-05-11	2003-12-04	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Use of inhibitors of the EGFR-mediated signal transduction for the treatment of benign prostatic hyperplasia (BPH)/prostatic hypertrophy
DE10221018A1 (de)	2002-05-11	2003-11-27	Boehringer Ingelheim Pharma	Verwendung von Hemmern der EGFR-vermittelten Signaltransduktion zur Behandlung von gutartiger Prostatahyperplasie (BPH)/Prostatahypertrophie
PE20040945A1 (es) *	2003-02-05	2004-12-14	Warner Lambert Co	Preparacion de quinazolinas substituidas
DE10307165A1 (de)	2003-02-20	2004-09-02	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, ihre Verwendung und Verfahren zu ihrer Herstellung
US7223749B2 (en) *	2003-02-20	2007-05-29	Boehringer Ingelheim International Gmbh	Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them
US20050043233A1 (en)	2003-04-29	2005-02-24	Boehringer Ingelheim International Gmbh	Combinations for the treatment of diseases involving cell proliferation, migration or apoptosis of myeloma cells or angiogenesis
DE10326186A1 (de)	2003-06-06	2004-12-23	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
US7456189B2 (en) *	2003-09-30	2008-11-25	Boehringer Ingelheim International Gmbh	Bicyclic heterocycles, medicaments containing these compounds, their use and processes for their preparation
DE10345875A1 (de)	2003-09-30	2005-04-21	Boehringer Ingelheim Pharma	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Vewendung und Verfahren zu ihrer Herstellung
DE10349113A1 (de) *	2003-10-17	2005-05-12	Boehringer Ingelheim Pharma	Verfahren zur Herstellung von Aminocrotonylverbindungen
US20060058311A1 (en) *	2004-08-14	2006-03-16	Boehringer Ingelheim International Gmbh	Combinations for the treatment of diseases involving cell proliferation
SI1948180T1 (sl)	2005-11-11	2013-06-28	Boehringer Ingelheim International Gmbh	Kombinacijsko zdravljenje raka, ki obsega EGFR/HER2 inhibitorje
JP5688877B2 (ja) *	2005-11-11	2015-03-25	ベーリンガーインゲルハイムインターナショナルゲゼルシャフトミットベシュレンクテルハフツング	癌疾患の治療用キナゾリン誘導体
US7960546B2 (en)	2006-01-26	2011-06-14	Boehringer Ingelheim International Gmbh	Process for preparing aminocrotonylamino-substituted quinazoline derivatives
ATE552835T1 (de) *	2006-09-18	2012-04-15	Boehringer Ingelheim Int	Verfahren zur behandlung von tumoren mit egfr- mutationen
UY31867A (es)	2008-06-06	2010-01-29	Boehringer Ingelheim Int	Nuevas formulaciones farmacéuticas sólidas que comprenden bibw 2992
WO2010081817A1 (en)	2009-01-14	2010-07-22	Boehringer Ingelheim International Gmbh	Method for treating colorectal cancer
DK2451445T3 (da)	2009-07-06	2019-06-24	Boehringer Ingelheim Int	Fremgangsmåde til at tørre bibw2992, dets salte og faste farmaceutiske formuleringer omfattende denne aktive ingrediens
WO2011069962A1 (en)	2009-12-07	2011-06-16	Boehringer Ingelheim International Gmbh	Bibw 2992 for use in the treatment of triple negative breast cancer

2000
- 2000-06-16 MX MXPA01012899A patent/MXPA01012899A/es active IP Right Grant
- 2000-06-16 HU HU0201900A patent/HUP0201900A3/hu unknown
- 2000-06-16 JP JP2001504901A patent/JP3686610B2/ja not_active Expired - Lifetime
- 2000-06-16 CN CNB00809201XA patent/CN1166645C/zh not_active Expired - Lifetime
- 2000-06-16 PT PT61169868T patent/PT1731511E/pt unknown
- 2000-06-16 YU YU90901A patent/YU90901A/sh unknown
- 2000-06-16 EP EP00936888A patent/EP1194418A1/de not_active Ceased
- 2000-06-16 CZ CZ20014497A patent/CZ302365B6/cs not_active IP Right Cessation
- 2000-06-16 DK DK06116986.8T patent/DK1731511T3/en active
- 2000-06-16 EE EEP200100695A patent/EE04748B1/xx not_active IP Right Cessation
- 2000-06-16 NZ NZ516633A patent/NZ516633A/en not_active IP Right Cessation
- 2000-06-16 IL IL14713300A patent/IL147133A0/xx active IP Right Grant
- 2000-06-16 EP EP06116986.8A patent/EP1731511B1/de not_active Expired - Lifetime
- 2000-06-16 TR TR2001/03692T patent/TR200103692T2/xx unknown
- 2000-06-16 ME MEP-455/08A patent/MEP45508A/xx unknown
- 2000-06-16 KR KR1020017016457A patent/KR100709909B1/ko active Protection Beyond IP Right Term
- 2000-06-16 UA UA2002010488A patent/UA71976C2/uk unknown
- 2000-06-16 CA CA002375259A patent/CA2375259C/en not_active Expired - Lifetime
- 2000-06-16 AU AU52214/00A patent/AU775285B2/en active Active
- 2000-06-16 WO PCT/EP2000/005547 patent/WO2000078735A1/de active IP Right Grant
- 2000-06-16 SK SK1845-2001A patent/SK287010B6/sk not_active IP Right Cessation
- 2000-06-16 EA EA200200008A patent/EA004981B1/ru active Protection Beyond IP Right Term
- 2000-06-16 ES ES06116986.8T patent/ES2552813T3/es not_active Expired - Lifetime
2001
- 2001-12-07 BG BG106189A patent/BG65890B1/bg active Active
- 2001-12-10 US US10/016,280 patent/US7220750B2/en not_active Expired - Lifetime
- 2001-12-17 IL IL147133A patent/IL147133A/en unknown
- 2001-12-18 NO NO20016185A patent/NO322094B1/no not_active IP Right Cessation
2002
- 2002-08-27 HK HK02106291.1A patent/HK1044769B/zh not_active IP Right Cessation
2007
- 2007-04-12 US US11/734,350 patent/US20070185091A1/en not_active Abandoned
2009
- 2009-11-24 US US12/624,875 patent/US20100069414A1/en not_active Abandoned
2012
- 2012-09-05 US US13/603,476 patent/US8722694B2/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
PT1731511E (pt)	2015-11-13
NZ516633A (en)	2004-09-24
IL147133A (en)	2006-09-05
SK18452001A3 (sk)	2002-04-04
EP1194418A1 (de)	2002-04-10
EP1731511B1 (de)	2015-08-12
CA2375259C (en)	2009-04-28
HK1044769A1 (en)	2002-11-01
DK1731511T3 (en)	2015-10-26
HUP0201900A2 (hu)	2002-12-28
NO20016185D0 (no)	2001-12-18
CA2375259A1 (en)	2000-12-28
KR100709909B1 (ko)	2007-04-24
CN1356990A (zh)	2002-07-03
JP3686610B2 (ja)	2005-08-24
US20120329778A1 (en)	2012-12-27
US8722694B2 (en)	2014-05-13
IL147133A0 (en)	2002-08-14
US20070185091A1 (en)	2007-08-09
BG65890B1 (bg)	2010-04-30
EA004981B1 (ru)	2004-10-28
EA200200008A1 (ru)	2002-06-27
JP2003502410A (ja)	2003-01-21
EP1731511A1 (de)	2006-12-13
UA71976C2 (en)	2005-01-17
CZ20014497A3 (cs)	2002-03-13
ES2552813T3 (es)	2015-12-02
AU775285B2 (en)	2004-07-29
SK287010B6 (sk)	2009-09-07
US7220750B2 (en)	2007-05-22
TR200103692T2 (tr)	2002-10-21
US20100069414A1 (en)	2010-03-18
YU90901A (sh)	2004-07-15
KR20020012290A (ko)	2002-02-15
BG106189A (bg)	2002-08-30
CZ302365B6 (cs)	2011-04-13
AU5221400A (en)	2001-01-09
EE04748B1 (et)	2006-12-15
MXPA01012899A (es)	2002-07-30
US20020169180A1 (en)	2002-11-14
MEP45508A (en)	2011-02-10
EE200100695A (et)	2003-02-17
NO20016185L (no)	2001-12-18
HK1044769B (zh)	2005-02-25
WO2000078735A1 (de)	2000-12-28
HUP0201900A3 (en)	2003-02-28
CN1166645C (zh)	2004-09-15

Publication	Publication Date	Title
NO322094B1 (no)	2006-08-14	Bicykliske heterocykler, medikamenter inneholdende disse forbindelser, deres anvendelse og fremgangsmate for fremstilling av dem.
US6972288B1 (en)	2005-12-06	4-amino-quinazoline and quinoline derivatives having an inhibitory effect on signal transduction mediated by tyrosine kinases
US6617329B2 (en)	2003-09-09	Aminoquinazolines and their use as medicaments
CA2417652C (en)	2008-10-28	Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them
US6627634B2 (en)	2003-09-30	Bicyclic heterocycles, pharmaceutical compositions containing them, their use, and processes for preparing them
CA2403152C (en)	2008-10-28	Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them
US20020082270A1 (en)	2002-06-27	Aminoquinazolines which inhibit signal transduction mediated by tyrosine kinases
EA009300B1 (ru)	2007-12-28	4-(n-фениламино)хиназолины/-хинолины в качестве ингибиторов тирозинкиназы
NO327747B1 (no)	2009-09-14	Bisykliske heterosykler, fremgangsmater for fremstilling av disse, fysiologisk akseptable salter av disse forbindelsene, farmasoytiske blandinger inneholdende disse forbindelsene samt anvendelse av disse forbindelsene for fremstilling av farmasoytiske preparater for behandling og forebygging av sykdom
HRP20030504A2 (en)	2005-06-30	Quinazoline derivatives, medicaments containing said compounds, their utilization and method for the production thereof
CA2417042A1 (en)	2002-03-07	Bicyclic heterocycles, pharmaceutical compositions containing these compounds, their use and processes for preparing them
JP5377332B2 (ja)	2013-12-25	二環式へテロ環、それらの化合物を含む薬剤、その使用及びその製法
DE10326186A1 (de)	2004-12-23	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung
PL212659B1 (pl)	2012-11-30	Bicykliczne heterocykle, kompozycje farmaceutyczne zawierajace te zwiazki i ich zastosowanie
DE19954816A1 (de)	2001-05-17	Bicyclische Heterocyclen, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung

Legal Events

Date	Code	Title	Description
2016-01-25	MM1K	Lapsed by not paying the annual fees