JP2009524604A5 - - Google Patents
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- Publication number
- JP2009524604A5 JP2009524604A5 JP2008551631A JP2008551631A JP2009524604A5 JP 2009524604 A5 JP2009524604 A5 JP 2009524604A5 JP 2008551631 A JP2008551631 A JP 2008551631A JP 2008551631 A JP2008551631 A JP 2008551631A JP 2009524604 A5 JP2009524604 A5 JP 2009524604A5
- Authority
- JP
- Japan
- Prior art keywords
- oxo
- pyrrolo
- dihydro
- methyl
- pyridin
- Prior art date
- Legal status (The legal status 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 status listed.)
- Granted
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- -1 alioxyl Chemical group 0.000 claims description 86
- 125000000217 alkyl group Chemical group 0.000 claims description 77
- 125000003118 aryl group Chemical group 0.000 claims description 73
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 61
- 125000001072 heteroaryl group Chemical group 0.000 claims description 51
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 41
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- 125000003545 alkoxy group Chemical group 0.000 claims description 28
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 21
- 150000001733 carboxylic acid esters Chemical group 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 21
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 18
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 125000003368 amide group Chemical group 0.000 claims description 16
- 150000002367 halogens Chemical group 0.000 claims description 16
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 12
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000005843 halogen group Chemical group 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 7
- 150000001735 carboxylic acids Chemical class 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 229910052717 sulfur Inorganic materials 0.000 claims description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- 150000001299 aldehydes Chemical class 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 5
- 239000003112 inhibitor Substances 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 3
- 229940123587 Cell cycle inhibitor Drugs 0.000 claims description 3
- 102000004190 Enzymes Human genes 0.000 claims description 3
- 108090000790 Enzymes Proteins 0.000 claims description 3
- DXVLWAKFFPXLLP-UHFFFAOYSA-N O=C1NC(C(=CC(F)=C2)N)=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(CC)CC)C2=O Chemical compound O=C1NC(C(=CC(F)=C2)N)=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(CC)CC)C2=O DXVLWAKFFPXLLP-UHFFFAOYSA-N 0.000 claims description 3
- 239000002168 alkylating agent Substances 0.000 claims description 3
- 229940100198 alkylating agent Drugs 0.000 claims description 3
- 230000002280 anti-androgenic effect Effects 0.000 claims description 3
- 230000003388 anti-hormonal effect Effects 0.000 claims description 3
- 230000000340 anti-metabolite Effects 0.000 claims description 3
- 239000000051 antiandrogen Substances 0.000 claims description 3
- 239000002256 antimetabolite Substances 0.000 claims description 3
- 229940100197 antimetabolite Drugs 0.000 claims description 3
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 3
- 239000002619 cytotoxin Substances 0.000 claims description 3
- 239000003534 dna topoisomerase inhibitor Substances 0.000 claims description 3
- 239000003102 growth factor Substances 0.000 claims description 3
- 229940127084 other anti-cancer agent Drugs 0.000 claims description 3
- 229940044693 topoisomerase inhibitor Drugs 0.000 claims description 3
- 229940030495 antiandrogen sex hormone and modulator of the genital system Drugs 0.000 claims description 2
- 239000003638 chemical reducing agent Substances 0.000 claims description 2
- 229940088598 enzyme Drugs 0.000 claims description 2
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000367 immunologic factor Substances 0.000 claims description 2
- 238000003780 insertion Methods 0.000 claims description 2
- 230000037431 insertion Effects 0.000 claims description 2
- 150000003951 lactams Chemical class 0.000 claims description 2
- 239000012280 lithium aluminium hydride Substances 0.000 claims description 2
- 230000000394 mitotic effect Effects 0.000 claims description 2
- BJFNQNOTLVCELU-UHFFFAOYSA-N 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]acetamide Chemical compound O=C1NC2=CC(NC(C)=O)=C(F)C=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(CC)CC)C2=O BJFNQNOTLVCELU-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 6
- 102000001253 Protein Kinase Human genes 0.000 claims 6
- 108060006633 protein kinase Proteins 0.000 claims 6
- 238000002360 preparation method Methods 0.000 claims 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 4
- 238000006243 chemical reaction Methods 0.000 claims 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims 4
- 239000000203 mixture Substances 0.000 claims 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 4
- 238000007363 ring formation reaction Methods 0.000 claims 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- JYGFTBXVXVMTGB-UHFFFAOYSA-N indolin-2-one Chemical compound C1=CC=C2NC(=O)CC2=C1 JYGFTBXVXVMTGB-UHFFFAOYSA-N 0.000 claims 3
- 229940049920 malate Drugs 0.000 claims 3
- 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 2
- 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 2
- YTUMZRDKADJBSW-UHFFFAOYSA-N 5-[2-(ethylamino)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(CCNCC)C2=O YTUMZRDKADJBSW-UHFFFAOYSA-N 0.000 claims 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 2
- PCKPVGOLPKLUHR-UHFFFAOYSA-N OH-Indolxyl Natural products C1=CC=C2C(O)=CNC2=C1 PCKPVGOLPKLUHR-UHFFFAOYSA-N 0.000 claims 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 230000004048 modification Effects 0.000 claims 2
- 238000012986 modification Methods 0.000 claims 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 2
- 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 1
- 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 1
- 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 1
- 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 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims 1
- BHIHOSLIDOOJFP-BTJKTKAUSA-N (z)-but-2-enedioic acid;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 OC(=O)\C=C/C(O)=O.O=C1NC2=CC=C(F)C=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(CC)CC)C2=O BHIHOSLIDOOJFP-BTJKTKAUSA-N 0.000 claims 1
- 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 1
- 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 1
- RDQPQUOOEQRQPN-UHFFFAOYSA-N 2-[(5-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=CC(Br)=CC=C4NC3=O)NC=2CCN1CCN1CCOCC1 RDQPQUOOEQRQPN-UHFFFAOYSA-N 0.000 claims 1
- HVOUGRMTEDHKQM-UHFFFAOYSA-N 2-[(5-bromo-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(Br)=CC=C4NC3=O)NC=2CCN1CCN1CCCCC1 HVOUGRMTEDHKQM-UHFFFAOYSA-N 0.000 claims 1
- XDDLRMCIDZLHNL-UHFFFAOYSA-N 2-[(5-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=C(Br)C=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(CC)CC)C2=O XDDLRMCIDZLHNL-UHFFFAOYSA-N 0.000 claims 1
- UMZQPGUMPPOEJO-UHFFFAOYSA-N 2-[(5-chloro-2-oxo-1h-indol-3-ylidene)methyl]-3-(4-fluorophenyl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one Chemical compound C1=CC(F)=CC=C1C(C=1C(=O)NCCC=1N1)=C1C=C1C2=CC(Cl)=CC=C2NC1=O UMZQPGUMPPOEJO-UHFFFAOYSA-N 0.000 claims 1
- UEHKGLXKCLZXOV-UHFFFAOYSA-N 2-[(5-chloro-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(Cl)=CC=C4NC3=O)NC=2CCN1CCN1CCOCC1 UEHKGLXKCLZXOV-UHFFFAOYSA-N 0.000 claims 1
- NLARLFPJKQVGTC-UHFFFAOYSA-N 2-[(5-chloro-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(Cl)=CC=C4NC3=O)NC=2CCN1CCN1CCCCC1 NLARLFPJKQVGTC-UHFFFAOYSA-N 0.000 claims 1
- SQOWNVKECIZHMJ-UHFFFAOYSA-N 2-[(5-chloro-2-oxo-1h-indol-3-ylidene)methyl]-3-phenyl-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one Chemical compound C12=CC(Cl)=CC=C2NC(=O)C1=CC=1NC=2CCNC(=O)C=2C=1C1=CC=CC=C1 SQOWNVKECIZHMJ-UHFFFAOYSA-N 0.000 claims 1
- CCIRQCXOVCNPBI-UHFFFAOYSA-N 2-[(5-chloro-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=C(Cl)C=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(CC)CC)C2=O CCIRQCXOVCNPBI-UHFFFAOYSA-N 0.000 claims 1
- YWUZNQJZVVLLJG-UHFFFAOYSA-N 2-[(5-chloro-2-oxo-1h-indol-3-ylidene)methyl]-5-[2-(dimethylamino)ethyl]-3-methyl-6,7-dihydro-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1NC2=CC=C(Cl)C=C2C1=CC(N1)=C(C)C2=C1CCN(CCN(C)C)C2=O YWUZNQJZVVLLJG-UHFFFAOYSA-N 0.000 claims 1
- XIXHUTATFFZDEK-UHFFFAOYSA-N 2-[(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-3-(4-fluorophenyl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one Chemical compound C1=CC(F)=CC=C1C(C=1C(=O)NCCC=1N1)=C1C=C1C2=CC(F)=CC=C2NC1=O XIXHUTATFFZDEK-UHFFFAOYSA-N 0.000 claims 1
- QBDDESDBDDPTQG-UHFFFAOYSA-N 2-[(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-3-methyl-5-(2-morpholin-4-ylethyl)-1h-pyrrolo[3,2-c]pyridin-4-one Chemical compound O=C1C=2C(C)=C(C=C3C4=CC(F)=CC=C4NC3=O)NC=2C=CN1CCN1CCOCC1 QBDDESDBDDPTQG-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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 1
- 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 1
- 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 1
- FIEQLJUMBKVVCS-UHFFFAOYSA-N 2-[(6-amino-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)=C(N)C=C4NC3=O)NC=2CCN1CCN1CCOCC1 FIEQLJUMBKVVCS-UHFFFAOYSA-N 0.000 claims 1
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Families Citing this family (54)
| 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 |
| CA2809331C (en) * | 2010-08-27 | 2018-09-25 | Merck Patent Gmbh | Triazolopyrazine derivatives |
| WO2014160521A1 (en) | 2013-03-15 | 2014-10-02 | Blueprint Medicines Corporation | Piperazine derivatives and their use as kit modulators |
| ES2776199T3 (es) | 2013-03-15 | 2020-07-29 | Aerie Pharmaceuticals Inc | Conjugados de compuestos de isoquinolina y prostaglandinas |
| MX365614B (es) | 2013-10-17 | 2019-06-07 | Blueprint Medicines Corp | Composiciones utiles para tratar trastornos relacionados con kit. |
| US9334263B2 (en) | 2013-10-17 | 2016-05-10 | Blueprint Medicines Corporation | Compositions useful for treating disorders related to kit |
| US9688680B2 (en) | 2014-08-04 | 2017-06-27 | Blueprint Medicines Corporation | Compositions useful for treating disorders related to kit |
| CN106535896B (zh) * | 2015-04-27 | 2019-06-21 | 江苏恒瑞医药股份有限公司 | 蛋白激酶抑制剂在制备治疗纤维化疾病的药物中的用途 |
| CA2992586A1 (en) | 2015-07-16 | 2017-01-19 | Array Biopharma, Inc. | Substituted pyrazolo[1,5-a]pyridine compounds as ret kinase inhibitors |
| BR112018001190A2 (pt) | 2015-07-24 | 2018-09-11 | Blueprint Medicines Corp | composições úteis para tratar distúrbios relacionados a kit e pdfgr |
| TWI750152B (zh) | 2016-03-01 | 2021-12-21 | 大陸商江蘇恆瑞醫藥股份有限公司 | 一種含有吡咯并六員雜環化合物或其可藥用鹽的藥物組成物 |
| TWI738729B (zh) | 2016-03-01 | 2021-09-11 | 大陸商江蘇恆瑞醫藥股份有限公司 | 一種含有吡咯并六員雜環化合物或其可藥用鹽的藥物組成物的製備方法 |
| US10779980B2 (en) | 2016-04-27 | 2020-09-22 | Synerz Medical, Inc. | Intragastric device for treating obesity |
| WO2018045091A1 (en) | 2016-08-31 | 2018-03-08 | Aerie Pharmaceuticals, Inc. | Ophthalmic compositions |
| US10417672B2 (en) | 2016-09-23 | 2019-09-17 | John Andrew GARCIA | Medium for creating standardized shared service offerings with template for custom unique prices |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| TWI752098B (zh) | 2016-10-10 | 2022-01-11 | 美商亞雷生物製藥股份有限公司 | 作為ret激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| JP6888101B2 (ja) | 2017-01-18 | 2021-06-16 | アレイ バイオファーマ インコーポレイテッド | ＲＥＴキナーゼ阻害剤としての置換ピラゾロ［１，５−ａ］ピラジン化合物 |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| CA3057872A1 (en) | 2017-03-31 | 2018-10-04 | Aerie Pharmaceuticals, Inc. | Aryl cyclopropyl-amino-isoquinolinyl amide compounds |
| WO2018183712A1 (en) | 2017-03-31 | 2018-10-04 | Blueprint Medicines Corporation | Pyrrolo[1,2-b]pyridazine compounds and compositions useful for treating disorders related to kit and pdgfr |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| TWI876442B (zh) | 2017-10-10 | 2025-03-11 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| CN111630054B (zh) | 2018-01-18 | 2023-05-09 | 奥瑞生物药品公司 | 作为RET激酶抑制剂的取代的吡唑并[3,4-d]嘧啶化合物 |
| EP3740486A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors |
| EP3740491A1 (en) | 2018-01-18 | 2020-11-25 | Array Biopharma, Inc. | Substituted pyrrolo[2,3-d]pyrimidines compounds as ret kinase inhibitors |
| CA3095730A1 (en) * | 2018-03-30 | 2019-10-03 | Aerie Pharmaceuticals, Inc. | Mono-(acid) salts of 6-aminoisoquinolines and uses thereof |
| ES2922314T3 (es) | 2018-09-10 | 2022-09-13 | Array Biopharma Inc | Compuestos heterocíclicos condensados como inhibidores de cinasa RET |
| AU2019337703B2 (en) | 2018-09-14 | 2023-02-02 | Aerie Pharmaceuticals, Inc. | Aryl cyclopropyl-amino-isoquinolinyl amide compounds |
| JP7883848B2 (ja) | 2018-11-06 | 2026-07-02 | ジエンス ヘンルイ メデイシンカンパニー リミテッド | 腫瘍を治療するための薬物の調製におけるファミチニブと組み合わせた抗ｐｄ－１抗体の使用 |
| US11421191B1 (en) | 2018-11-15 | 2022-08-23 | Ecolab Usa Inc. | Acidic cleaner |
| SG11202111244XA (en) | 2019-04-12 | 2021-11-29 | Blueprint Medicines Corp | Pyrrolotriazine derivatives for treating kit- and pdgfra-mediated diseases |
| HUE064283T2 (hu) | 2019-04-12 | 2024-02-28 | Blueprint Medicines Corp | Az (S)-1-(4-fluorofenil)-1-(2-(4-(6-(1-metil-1H-pirazol-4-il)pirrolo[2,1-f][1,2,4]triazin-4-il) piperazinil)-pirimidin-5-il)etán-1-amin kristályos formái és elõállítási eljárásai |
| CN111068661B (zh) * | 2019-12-12 | 2021-10-08 | 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 |
| CN113149891B (zh) * | 2020-01-07 | 2024-02-02 | 南京药石科技股份有限公司 | 一种2-氨基-2-（1-甲基-4-哌啶基）乙醇的制备方法 |
Family Cites Families (14)
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| GB9423997D0 (en) * | 1994-11-28 | 1995-01-11 | Erba Carlo Spa | Substituted 3-arylidene-7-azaoxindole compounds and process for their preparation |
| US5866702A (en) | 1996-08-02 | 1999-02-02 | Cv Therapeutics, Incorporation | Purine inhibitors of cyclin dependent kinase 2 |
| US6114371A (en) | 1997-06-20 | 2000-09-05 | Sugen, Inc. | 3-(cyclohexanoheteroarylidenyl)-2-indolinone protein tyrosine kinase inhibitors |
| KR100743287B1 (ko) * | 1998-05-29 | 2007-07-26 | 수젠, 인크. | 피롤기로 치환된 2-인돌리논 단백질 인산화 효소 억제제 |
| US6610688B2 (en) | 1999-12-21 | 2003-08-26 | Sugen, Inc. | 4-substituted 7-aza-indolin-2-ones and their use as protein kinase inhibitors |
| WO2001064681A2 (en) * | 2000-02-28 | 2001-09-07 | Sugen, Inc. | 3-(pyrolyllactone)-2-indolinone compounds as kinase inhibitors |
| JP2003535847A (ja) * | 2000-06-02 | 2003-12-02 | スージェン・インコーポレーテッド | 蛋白質キナーゼ／ホスファターゼ阻害剤としてのインドリノン誘導体 |
| WO2002002551A1 (en) * | 2000-06-30 | 2002-01-10 | Sugen, Inc. | 4-heteroaryl-3-heteroarylidenyl-2-indolinones and their use as protein kinase inhibitors |
| US20030225127A1 (en) | 2000-08-11 | 2003-12-04 | Bender David Michael | Heterocyclic sulfonamide derivatives |
| PE20020776A1 (es) * | 2000-12-20 | 2002-08-22 | Sugen Inc | Indolinonas 4-aril sustituidas |
| EP1432708B1 (en) * | 2001-09-24 | 2005-11-30 | Bayer Pharmaceuticals Corporation | Preparation and use of 1,5,6,7-tetrahydropyrrolo 3,2-c]pyridine derivatives for treatment of obesity |
| TWI259081B (en) * | 2001-10-26 | 2006-08-01 | Sugen Inc | Treatment of acute myeloid leukemia with indolinone compounds |
| AR056560A1 (es) * | 2005-10-06 | 2007-10-10 | Astrazeneca Ab | Pirrolopiridinonas como moduladores cb1 |
| 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 |
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