JP5256047B2 - ピロロ［３，２−ｃ］ピリジン−４−オン２−インドリノン（ｉｎｄｏｌｉｎｏｎｅ）プロテインキナーゼ阻害剤 - Google Patents
ピロロ［３，２−ｃ］ピリジン−４−オン２−インドリノン（ｉｎｄｏｌｉｎｏｎｅ）プロテインキナーゼ阻害剤 Download PDFInfo
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- JP5256047B2 JP5256047B2 JP2008551631A JP2008551631A JP5256047B2 JP 5256047 B2 JP5256047 B2 JP 5256047B2 JP 2008551631 A JP2008551631 A JP 2008551631A JP 2008551631 A JP2008551631 A JP 2008551631A JP 5256047 B2 JP5256047 B2 JP 5256047B2
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- Prior art keywords
- oxo
- pyrrolo
- dihydro
- methyl
- tetrahydro
- Prior art date
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- 239000003909 protein kinase inhibitor Substances 0.000 title description 2
- JVCFBZCNVSKWHX-UHFFFAOYSA-N 1,3-dihydroindol-2-one;pyrrolo[3,2-c]pyridin-4-one Chemical compound C1=CC=C2NC(=O)CC2=C1.O=C1N=CC=C2N=CC=C12 JVCFBZCNVSKWHX-UHFFFAOYSA-N 0.000 title 1
- 229940043355 kinase inhibitor Drugs 0.000 title 1
- -1 alioxyl Chemical group 0.000 claims description 341
- 150000001875 compounds Chemical class 0.000 claims description 219
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 177
- 239000000203 mixture Substances 0.000 claims description 155
- 125000000217 alkyl group Chemical group 0.000 claims description 154
- 125000003118 aryl group Chemical group 0.000 claims description 114
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 90
- 125000001072 heteroaryl group Chemical group 0.000 claims description 84
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 78
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 77
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 65
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 65
- 150000003839 salts Chemical class 0.000 claims description 63
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 60
- 125000003545 alkoxy group Chemical group 0.000 claims description 59
- 238000000034 method Methods 0.000 claims description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 55
- 102000001253 Protein Kinase Human genes 0.000 claims description 52
- 108060006633 protein kinase Proteins 0.000 claims description 52
- 125000005843 halogen group Chemical group 0.000 claims description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 39
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 38
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 36
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 34
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 33
- 239000001257 hydrogen Substances 0.000 claims description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims description 33
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 33
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 32
- 125000003342 alkenyl group Chemical group 0.000 claims description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 30
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 28
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 28
- 230000008569 process Effects 0.000 claims description 28
- 150000001733 carboxylic acid esters Chemical group 0.000 claims description 27
- 125000000304 alkynyl group Chemical group 0.000 claims description 26
- 229910052736 halogen Inorganic materials 0.000 claims description 25
- 150000002367 halogens Chemical group 0.000 claims description 23
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 19
- 125000003368 amide group Chemical group 0.000 claims description 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 18
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 17
- 239000003102 growth factor Substances 0.000 claims description 17
- 238000004519 manufacturing process Methods 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 16
- 239000003112 inhibitor Substances 0.000 claims description 16
- 229910052760 oxygen Inorganic materials 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 239000002253 acid Substances 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 13
- 102000004190 Enzymes Human genes 0.000 claims description 12
- 108090000790 Enzymes Proteins 0.000 claims description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 12
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims description 12
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 11
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 11
- 230000004048 modification Effects 0.000 claims description 11
- 238000012986 modification Methods 0.000 claims description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000001188 haloalkyl group Chemical group 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 9
- 150000001299 aldehydes Chemical class 0.000 claims description 9
- 150000001735 carboxylic acids Chemical class 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 229940079593 drug Drugs 0.000 claims description 9
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 9
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 8
- 229940100198 alkylating agent Drugs 0.000 claims description 8
- 239000002168 alkylating agent Substances 0.000 claims description 8
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 8
- 238000007363 ring formation reaction Methods 0.000 claims description 8
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 7
- 229940123587 Cell cycle inhibitor Drugs 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 7
- 230000002280 anti-androgenic effect Effects 0.000 claims description 7
- 230000003388 anti-hormonal effect Effects 0.000 claims description 7
- 230000000340 anti-metabolite Effects 0.000 claims description 7
- 239000000051 antiandrogen Substances 0.000 claims description 7
- 229940100197 antimetabolite Drugs 0.000 claims description 7
- 239000002256 antimetabolite Substances 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims description 7
- 239000002904 solvent Substances 0.000 claims description 7
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 claims description 6
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 6
- 239000002619 cytotoxin Substances 0.000 claims description 6
- 229940088598 enzyme Drugs 0.000 claims description 6
- 238000003780 insertion Methods 0.000 claims description 6
- 230000037431 insertion Effects 0.000 claims description 6
- 230000000394 mitotic effect Effects 0.000 claims description 6
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 6
- RWTZSDZKFPETKM-UHFFFAOYSA-N 5-[2-(diethylamino)ethyl]-3-methyl-2-[(4-methyl-2-oxo-1h-indol-3-ylidene)methyl]-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1NC2=CC=CC(C)=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(CC)CC)C2=O RWTZSDZKFPETKM-UHFFFAOYSA-N 0.000 claims description 5
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 229940049920 malate Drugs 0.000 claims description 5
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 5
- 239000003607 modifier Substances 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 5
- FPYCSQMCBIGNHK-UHFFFAOYSA-N 2-[(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-3-methyl-5-(2-morpholin-4-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1C=2C(C)=C(C=C3C4=CC(F)=CC=C4NC3=O)NC=2CCN1CCN1CCOCC1 FPYCSQMCBIGNHK-UHFFFAOYSA-N 0.000 claims description 4
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 4
- GKEYKDOLBLYGRB-UHFFFAOYSA-N 5-[2-(diethylamino)ethyl]-2-[(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-3-methyl-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1NC2=CC=C(F)C=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(CC)CC)C2=O GKEYKDOLBLYGRB-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 239000000367 immunologic factor Substances 0.000 claims description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 4
- 239000001630 malic acid Substances 0.000 claims description 4
- 229940127084 other anti-cancer agent Drugs 0.000 claims description 4
- JRIXWVXFPBEXSS-HNNXBMFYSA-N (2s)-n-[3-[[5-[2-(diethylamino)ethyl]-3-methyl-4-oxo-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-2-yl]methylidene]-5-fluoro-2-oxo-1h-indol-6-yl]-2-hydroxypropanamide Chemical compound O=C1NC2=CC(NC(=O)[C@H](C)O)=C(F)C=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(CC)CC)C2=O JRIXWVXFPBEXSS-HNNXBMFYSA-N 0.000 claims description 3
- QUTUKWADAWVVHK-INIZCTEOSA-N (2s)-n-[5-fluoro-3-[[3-methyl-4-oxo-5-(2-piperidin-1-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-2-yl]methylidene]-2-oxo-1h-indol-6-yl]-2-hydroxypropanamide Chemical compound C1=2C=C(F)C(NC(=O)[C@@H](O)C)=CC=2NC(=O)C1=CC(=C(C=1C2=O)C)NC=1CCN2CCN1CCCCC1 QUTUKWADAWVVHK-INIZCTEOSA-N 0.000 claims description 3
- KOTAOQUKLFHNNU-HNNXBMFYSA-N (2s)-n-[5-fluoro-3-[[3-methyl-4-oxo-5-(2-pyrrolidin-1-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-2-yl]methylidene]-2-oxo-1h-indol-6-yl]-2-hydroxypropanamide Chemical compound C1=2C=C(F)C(NC(=O)[C@@H](O)C)=CC=2NC(=O)C1=CC(=C(C=1C2=O)C)NC=1CCN2CCN1CCCC1 KOTAOQUKLFHNNU-HNNXBMFYSA-N 0.000 claims description 3
- NOFGBTHOCMANDH-HNNXBMFYSA-N (2s)-n-[5-fluoro-3-[[3-methyl-5-(2-morpholin-4-ylethyl)-4-oxo-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-2-yl]methylidene]-2-oxo-1h-indol-6-yl]-2-hydroxypropanamide Chemical compound C1=2C=C(F)C(NC(=O)[C@@H](O)C)=CC=2NC(=O)C1=CC(=C(C=1C2=O)C)NC=1CCN2CCN1CCOCC1 NOFGBTHOCMANDH-HNNXBMFYSA-N 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 3
- RXFRTRIPNBVBNP-UHFFFAOYSA-N 2-[(4-bromo-2-oxo-1h-indol-3-ylidene)methyl]-3-methyl-5-(2-morpholin-4-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1C=2C(C)=C(C=C3C4=C(Br)C=CC=C4NC3=O)NC=2CCN1CCN1CCOCC1 RXFRTRIPNBVBNP-UHFFFAOYSA-N 0.000 claims description 3
- OKJWHYRNQFMLDB-UHFFFAOYSA-N 2-[(4-bromo-2-oxo-1h-indol-3-ylidene)methyl]-5-[2-(diethylamino)ethyl]-3-methyl-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1NC2=CC=CC(Br)=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(CC)CC)C2=O OKJWHYRNQFMLDB-UHFFFAOYSA-N 0.000 claims description 3
- IUKYRKPDOZZLDR-UHFFFAOYSA-N 2-[(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-3-methyl-5-(2-piperidin-1-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1C=2C(C)=C(C=C3C4=CC(F)=CC=C4NC3=O)NC=2CCN1CCN1CCCCC1 IUKYRKPDOZZLDR-UHFFFAOYSA-N 0.000 claims description 3
- SJFRHARDEVHAPJ-UHFFFAOYSA-N 2-[(5-methoxy-2-oxo-1h-indol-3-ylidene)methyl]-3-methyl-5-(2-morpholin-4-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound C12=CC(OC)=CC=C2NC(=O)C1=CC(=C(C=1C2=O)C)NC=1CCN2CCN1CCOCC1 SJFRHARDEVHAPJ-UHFFFAOYSA-N 0.000 claims description 3
- MLYFVYUDRUWXSL-UHFFFAOYSA-N 2-[(5-methoxy-2-oxo-1h-indol-3-ylidene)methyl]-3-methyl-5-(2-piperidin-1-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound C12=CC(OC)=CC=C2NC(=O)C1=CC(=C(C=1C2=O)C)NC=1CCN2CCN1CCCCC1 MLYFVYUDRUWXSL-UHFFFAOYSA-N 0.000 claims description 3
- AJXSIJNOAMIYEW-UHFFFAOYSA-N 2-[(5-methoxy-2-oxo-1h-indol-3-ylidene)methyl]-3-methyl-5-(2-pyrrolidin-1-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound C12=CC(OC)=CC=C2NC(=O)C1=CC(=C(C=1C2=O)C)NC=1CCN2CCN1CCCC1 AJXSIJNOAMIYEW-UHFFFAOYSA-N 0.000 claims description 3
- KTWQCWMUUBUVBG-UHFFFAOYSA-N 2-[(6-amino-5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-5-[2-(diethylamino)ethyl]-3-methyl-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1NC2=CC(N)=C(F)C=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(CC)CC)C2=O KTWQCWMUUBUVBG-UHFFFAOYSA-N 0.000 claims description 3
- WOTHSXDVNKMLNV-UHFFFAOYSA-N 2-[(7-bromo-5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-3-methyl-5-(2-pyrrolidin-1-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1C=2C(C)=C(C=C3C4=C(C(=CC(F)=C4)Br)NC3=O)NC=2CCN1CCN1CCCC1 WOTHSXDVNKMLNV-UHFFFAOYSA-N 0.000 claims description 3
- ZUONONPOHLEUTL-UHFFFAOYSA-N 2-[[4-(2,3-difluorophenyl)-2-oxo-1h-indol-3-ylidene]methyl]-3-methyl-5-(2-morpholin-4-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound N1C=2CCN(CCN3CCOCC3)C(=O)C=2C(C)=C1C=C(C=12)C(=O)NC2=CC=CC=1C1=CC=CC(F)=C1F ZUONONPOHLEUTL-UHFFFAOYSA-N 0.000 claims description 3
- YAIHLCYGLNDMOA-UHFFFAOYSA-N 2-[[4-(2,3-difluorophenyl)-2-oxo-1h-indol-3-ylidene]methyl]-3-methyl-5-(2-piperidin-1-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound N1C=2CCN(CCN3CCCCC3)C(=O)C=2C(C)=C1C=C(C=12)C(=O)NC2=CC=CC=1C1=CC=CC(F)=C1F YAIHLCYGLNDMOA-UHFFFAOYSA-N 0.000 claims description 3
- XAMVOEZUXPYRPW-UHFFFAOYSA-N 2-[[4-(2,3-difluorophenyl)-2-oxo-1h-indol-3-ylidene]methyl]-3-methyl-5-(2-pyrrolidin-1-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound N1C=2CCN(CCN3CCCC3)C(=O)C=2C(C)=C1C=C(C=12)C(=O)NC2=CC=CC=1C1=CC=CC(F)=C1F XAMVOEZUXPYRPW-UHFFFAOYSA-N 0.000 claims description 3
- BRMOJAAVEHEYLQ-UHFFFAOYSA-N 2-[[4-(2,6-difluorophenyl)-2-oxo-1h-indol-3-ylidene]methyl]-3-methyl-5-(2-piperidin-1-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound N1C=2CCN(CCN3CCCCC3)C(=O)C=2C(C)=C1C=C(C=12)C(=O)NC2=CC=CC=1C1=C(F)C=CC=C1F BRMOJAAVEHEYLQ-UHFFFAOYSA-N 0.000 claims description 3
- HDUWVVSPFMVPMU-UHFFFAOYSA-N 2-[[4-(2-hydroxyethyl)-2-oxo-1h-indol-3-ylidene]methyl]-3-methyl-5-(2-morpholin-4-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1C=2C(C)=C(C=C3C4=C(CCO)C=CC=C4NC3=O)NC=2CCN1CCN1CCOCC1 HDUWVVSPFMVPMU-UHFFFAOYSA-N 0.000 claims description 3
- OQTBFVHHJIYKNW-UHFFFAOYSA-N 2-[[4-(2-hydroxyethyl)-2-oxo-1h-indol-3-ylidene]methyl]-3-methyl-5-(2-piperidin-1-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1C=2C(C)=C(C=C3C4=C(CCO)C=CC=C4NC3=O)NC=2CCN1CCN1CCCCC1 OQTBFVHHJIYKNW-UHFFFAOYSA-N 0.000 claims description 3
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- QAFCZOLNYBRZQX-UHFFFAOYSA-N 2-[[4-(3-fluorophenyl)-2-oxo-1h-indol-3-ylidene]methyl]-3-methyl-5-(2-piperidin-1-ylethyl)-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound N1C=2CCN(CCN3CCCCC3)C(=O)C=2C(C)=C1C=C(C=12)C(=O)NC2=CC=CC=1C1=CC=CC(F)=C1 QAFCZOLNYBRZQX-UHFFFAOYSA-N 0.000 claims description 3
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Landscapes
- Health & Medical Sciences (AREA)
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- Heart & Thoracic Surgery (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200610003229.6 | 2006-01-27 | ||
| CN200610003229 | 2006-01-27 | ||
| CN 200610065001 CN101007814A (zh) | 2006-01-27 | 2006-03-15 | 吡咯并六元杂环化合物及其在医药上的用途 |
| CN200610065001.X | 2006-03-15 | ||
| CN200610122000.4 | 2006-08-30 | ||
| CN2006101220004A CN101007815B (zh) | 2006-01-27 | 2006-08-30 | 吡咯并六元杂环化合物及其在医药上的用途 |
| PCT/CN2007/000256 WO2007085188A1 (en) | 2006-01-27 | 2007-01-24 | Pyrrolo [3,2-c] pyridine-4-one 2-indolinone protein kinase inhibitors |
Publications (3)
| Publication Number | Publication Date |
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| JP2009524604A JP2009524604A (ja) | 2009-07-02 |
| JP2009524604A5 JP2009524604A5 (enExample) | 2013-05-02 |
| JP5256047B2 true JP5256047B2 (ja) | 2013-08-07 |
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| JP2008551631A Expired - Fee Related JP5256047B2 (ja) | 2006-01-27 | 2007-01-24 | ピロロ［３，２−ｃ］ピリジン−４−オン２−インドリノン（ｉｎｄｏｌｉｎｏｎｅ）プロテインキナーゼ阻害剤 |
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| US (3) | US8012966B2 (enExample) |
| EP (1) | EP1973910B1 (enExample) |
| JP (1) | JP5256047B2 (enExample) |
| KR (1) | KR101452520B1 (enExample) |
| AU (1) | AU2007209689B2 (enExample) |
| BR (1) | BRPI0707312B1 (enExample) |
| CA (1) | CA2636701C (enExample) |
| DK (1) | DK1973910T3 (enExample) |
| ES (1) | ES2426448T3 (enExample) |
| MX (1) | MX2008009557A (enExample) |
| PL (1) | PL1973910T3 (enExample) |
| PT (1) | PT1973910E (enExample) |
| WO (1) | WO2007085188A1 (enExample) |
| ZA (1) | ZA200806313B (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111068661A (zh) * | 2019-12-12 | 2020-04-28 | 中山大学 | 一种非金属共掺杂的碳负载金属纳米颗粒催化剂及其制备方法和应用 |
Families Citing this family (53)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8455513B2 (en) | 2007-01-10 | 2013-06-04 | Aerie Pharmaceuticals, Inc. | 6-aminoisoquinoline compounds |
| WO2008138184A1 (fr) | 2007-05-14 | 2008-11-20 | Shanghai Hengrui Pharmaceutical Co.Ltd. | Dérivés de pyrrolo-azacycles, leur procédé de fabrication et leur utilisation en tant qu'inhibiteurs de protéine kinases |
| WO2008138232A1 (en) * | 2007-05-14 | 2008-11-20 | Shanghai Hengrui Pharmaceutical Co., Ltd. | Pyrrolo-nitrogenous heterocyclic derivatives, the preparation and the pharmaceutical use thereof |
| CN101367801B (zh) * | 2007-08-15 | 2011-01-12 | 上海恒瑞医药有限公司 | 吡咯并六元n杂环羟基吗啡啉类衍生物的制备方法及其在医药上的应用 |
| ES2423932T3 (es) | 2007-08-27 | 2013-09-25 | Basf Se | Compuestos de pirazol para controlar plagas de invertebrados |
| CA2736177A1 (en) | 2007-09-06 | 2009-03-12 | Boston Biomedical, Inc. | Compositions of kinase inhibitors and their use for treatment of cancer and other diseases related to kinases |
| CN102015705B (zh) * | 2008-02-26 | 2013-11-13 | 武田药品工业株式会社 | 稠合的杂环衍生物及其用途 |
| CN102137866A (zh) * | 2008-06-30 | 2011-07-27 | 赛林药物股份有限公司 | 羟吲哚化合物 |
| US8450344B2 (en) | 2008-07-25 | 2013-05-28 | Aerie Pharmaceuticals, Inc. | Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds |
| WO2010126626A2 (en) | 2009-05-01 | 2010-11-04 | Aerie Pharmaceuticals, Inc. | Dual mechanism inhibitors for the treatment of disease |
| ES2472918T3 (es) | 2009-07-06 | 2014-07-03 | Basf Se | Compuestos de piridazina para controlar plagas de invertebrados |
| JP2013500246A (ja) | 2009-07-24 | 2013-01-07 | ビーエーエスエフ ソシエタス・ヨーロピア | 無脊椎動物系害虫防除用ピリジン誘導体化合物 |
| US8927718B2 (en) * | 2009-08-26 | 2015-01-06 | Takeda Pharmaceutical Company Limited | Fused heterocyclic ring derivative and use thereof |
| CN102146082A (zh) * | 2010-02-04 | 2011-08-10 | 江苏恒瑞医药股份有限公司 | 吡咯并n杂环类衍生物的可药用的盐、其制备方法及其在医药上的应用 |
| BR122019024201B1 (pt) | 2010-05-20 | 2021-08-03 | Array Biopharma Inc | Composto macrocíclico como inibidores de trk quinase, seu uso, e composição farmacêutica |
| US10420665B2 (en) | 2010-06-13 | 2019-09-24 | W. L. Gore & Associates, Inc. | Intragastric device for treating obesity |
| US9526648B2 (en) | 2010-06-13 | 2016-12-27 | Synerz Medical, Inc. | Intragastric device for treating obesity |
| US10010439B2 (en) | 2010-06-13 | 2018-07-03 | Synerz Medical, Inc. | Intragastric device for treating obesity |
| US8628554B2 (en) | 2010-06-13 | 2014-01-14 | Virender K. Sharma | Intragastric device for treating obesity |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111068661A (zh) * | 2019-12-12 | 2020-04-28 | 中山大学 | 一种非金属共掺杂的碳负载金属纳米颗粒催化剂及其制备方法和应用 |
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| AU2007209689B2 (en) | 2012-03-15 |
| BRPI0707312B1 (pt) | 2022-06-07 |
| US20110301353A1 (en) | 2011-12-08 |
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| US8012966B2 (en) | 2011-09-06 |
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| ES2426448T3 (es) | 2013-10-23 |
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| KR20080091258A (ko) | 2008-10-09 |
| CA2636701A1 (en) | 2007-08-02 |
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| HK1115879A1 (en) | 2008-12-12 |
| EP1973910B1 (en) | 2013-06-26 |
| JP2009524604A (ja) | 2009-07-02 |
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