JP2007532580A5 - - Google Patents
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- JP2007532580A5 JP2007532580A5 JP2007507576A JP2007507576A JP2007532580A5 JP 2007532580 A5 JP2007532580 A5 JP 2007532580A5 JP 2007507576 A JP2007507576 A JP 2007507576A JP 2007507576 A JP2007507576 A JP 2007507576A JP 2007532580 A5 JP2007532580 A5 JP 2007532580A5
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- Japan
- Prior art keywords
- optionally substituted
- substituted
- methyl
- formula
- dihydro
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 43
- -1 6-Chloro-2,2,4-trimethyl-3,4-dihydro-2H-1,4-benzoxazin-8-yl Chemical group 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 22
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 15
- 150000002430 hydrocarbons Chemical group 0.000 claims description 14
- 229910052757 nitrogen Chemical group 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 150000002367 halogens Chemical class 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 4
- 125000004914 dipropylamino group Chemical group C(CC)N(CCC)* 0.000 claims description 4
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- AHWUHMSUNBLRGI-UHFFFAOYSA-N 5-(2,4-dimethylphenyl)-1-heptan-4-yl-3-methylquinolin-4-one Chemical compound C1=CC=C2N(C(CCC)CCC)C=C(C)C(=O)C2=C1C1=CC=C(C)C=C1C AHWUHMSUNBLRGI-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 9
- 125000005842 heteroatom Chemical group 0.000 claims 9
- 229910052760 oxygen Inorganic materials 0.000 claims 9
- 239000001301 oxygen Substances 0.000 claims 9
- 229910052717 sulfur Inorganic materials 0.000 claims 9
- 239000011593 sulfur Chemical group 0.000 claims 9
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 8
- 150000002431 hydrogen Chemical class 0.000 claims 6
- 239000003814 drug Substances 0.000 claims 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical class C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 3
- 239000005977 Ethylene Substances 0.000 claims 3
- 125000001072 heteroaryl group Chemical group 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 125000001841 imino group Chemical group [H]N=* 0.000 claims 3
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims 3
- 239000000651 prodrug Substances 0.000 claims 3
- 229940002612 prodrug Drugs 0.000 claims 3
- 208000017194 Affective disease Diseases 0.000 claims 2
- 208000019901 Anxiety disease Diseases 0.000 claims 2
- 208000019022 Mood disease Diseases 0.000 claims 2
- 230000036506 anxiety Effects 0.000 claims 2
- MTZQAGJQAFMTAQ-UHFFFAOYSA-N ethyl benzoate Chemical compound CCOC(=O)C1=CC=CC=C1 MTZQAGJQAFMTAQ-UHFFFAOYSA-N 0.000 claims 2
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical group [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 claims 2
- 230000003449 preventive effect Effects 0.000 claims 2
- 150000003839 salts Chemical class 0.000 claims 2
- 125000000335 thiazolyl group Chemical group 0.000 claims 2
- WTOCEEDDEGRNFX-UHFFFAOYSA-N 1,3,6-trimethyl-5-phenyl-7h-pyrrolo[2,3-d]pyrimidine-2,4-dione Chemical compound CC=1NC=2N(C)C(=O)N(C)C(=O)C=2C=1C1=CC=CC=C1 WTOCEEDDEGRNFX-UHFFFAOYSA-N 0.000 claims 1
- MMCQERJICAXMTN-UHFFFAOYSA-N 1,7-dimethyl-4-oxo-3,5-diphenyl-2H-quinazoline-6-carboxylic acid Chemical compound CC1=CC2=C(C(=C1C(=O)O)C3=CC=CC=C3)C(=O)N(CN2C)C4=CC=CC=C4 MMCQERJICAXMTN-UHFFFAOYSA-N 0.000 claims 1
- MWSVXVOHPLLHKV-UHFFFAOYSA-N 1-cyclobutyl-6,8-difluoro-7-(4-methylpiperazin-1-yl)-4-oxo-5-phenoxyquinoline-3-carboxylic acid Chemical compound C1CN(C)CCN1C1=C(F)C(OC=2C=CC=CC=2)=C2C(=O)C(C(O)=O)=CN(C3CCC3)C2=C1F MWSVXVOHPLLHKV-UHFFFAOYSA-N 0.000 claims 1
- DNRSCQMUFQAONZ-UHFFFAOYSA-N 1-cyclopropyl-6,8-difluoro-7-(4-methylpiperazin-1-yl)-4-oxo-5-phenylsulfanylquinoline-3-carboxylic acid Chemical compound C1CN(C)CCN1C1=C(F)C(SC=2C=CC=CC=2)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F DNRSCQMUFQAONZ-UHFFFAOYSA-N 0.000 claims 1
- SHGYPOPMGYRISE-UHFFFAOYSA-N 1-cyclopropyl-7-(2,6-dimethylpyridin-4-yl)-6,8-difluoro-4-oxo-5-phenylsulfanylquinoline-3-carboxylic acid Chemical compound CC1=NC(C)=CC(C=2C(=C3C(C(C(C(O)=O)=CN3C3CC3)=O)=C(SC=3C=CC=CC=3)C=2F)F)=C1 SHGYPOPMGYRISE-UHFFFAOYSA-N 0.000 claims 1
- UGJOZNVBDVWNFG-UHFFFAOYSA-N 2,2,4-trimethyl-8-(6-oxo-4,5-dihydro-1h-pyridazin-3-yl)-1,4-benzoxazin-3-one Chemical compound CN1C(=O)C(C)(C)OC2=C1C=CC=C2C1=NNC(=O)CC1 UGJOZNVBDVWNFG-UHFFFAOYSA-N 0.000 claims 1
- LWTIGYSPAXKMDG-UHFFFAOYSA-N 2,3-dihydro-1h-imidazole Chemical compound C1NC=CN1 LWTIGYSPAXKMDG-UHFFFAOYSA-N 0.000 claims 1
- RXFHTXAPXGDKTG-UHFFFAOYSA-N 2-(dipropylamino)-3,7-dimethyl-5-(2,4,6-trimethylphenyl)pyrrolo[2,3-d]pyrimidin-4-one Chemical compound C1=2C(=O)N(C)C(N(CCC)CCC)=NC=2N(C)C=C1C1=C(C)C=C(C)C=C1C RXFHTXAPXGDKTG-UHFFFAOYSA-N 0.000 claims 1
- GNSFIYPWJBSHNF-UHFFFAOYSA-N 2-methyl-1-pentan-3-yl-4-(2,4,6-trimethylphenyl)indazol-3-one Chemical compound C1=CC=C2N(C(CC)CC)N(C)C(=O)C2=C1C1=C(C)C=C(C)C=C1C GNSFIYPWJBSHNF-UHFFFAOYSA-N 0.000 claims 1
- HRFTZVGHMNREEM-UHFFFAOYSA-N 3,6-dibenzyl-1-cyclopentyl-5H-pyrazolo[3,4-d]pyrimidin-4-one Chemical compound N1C=2N(C3CCCC3)N=C(CC=3C=CC=CC=3)C=2C(=O)N=C1CC1=CC=CC=C1 HRFTZVGHMNREEM-UHFFFAOYSA-N 0.000 claims 1
- AYEDRAIEQAHOPS-UHFFFAOYSA-N 3-(2,4-dimethylphenyl)-6-(dipropylamino)-1,5-dimethylpyrazolo[3,4-d]pyrimidin-4-one Chemical compound C1=2C(=O)N(C)C(N(CCC)CCC)=NC=2N(C)N=C1C1=CC=C(C)C=C1C AYEDRAIEQAHOPS-UHFFFAOYSA-N 0.000 claims 1
- KWHUOQCJQPZBKC-UHFFFAOYSA-N 4,6-dimethyl-8-(4-methyl-6-oxo-4,5-dihydro-1h-pyridazin-3-yl)-1,4-benzoxazin-3-one Chemical compound CC1CC(=O)NN=C1C1=CC(C)=CC2=C1OCC(=O)N2C KWHUOQCJQPZBKC-UHFFFAOYSA-N 0.000 claims 1
- MWNLJDWMPXPVDS-UHFFFAOYSA-N 4,6-dimethyl-8-(6-oxo-4,5-dihydro-1h-pyridazin-3-yl)-1,4-benzoxazin-3-one Chemical compound CN1C(=O)COC2=C1C=C(C)C=C2C1=NNC(=O)CC1 MWNLJDWMPXPVDS-UHFFFAOYSA-N 0.000 claims 1
- OGJCAECEPPRLOE-UHFFFAOYSA-N 4-(8-benzyl-4-methyl-2,3-dihydro-1,4-benzoxazin-6-yl)-2,4-dioxobutanoic acid Chemical compound C1=C(C(=O)CC(=O)C(O)=O)C=C2N(C)CCOC2=C1CC1=CC=CC=C1 OGJCAECEPPRLOE-UHFFFAOYSA-N 0.000 claims 1
- KKEGOCWGBQYACU-UHFFFAOYSA-N 6-(4-bromophenyl)-1-(4-methoxyphenyl)-5-methyl-7-oxopyrazolo[4,3-d]pyrimidine-3-carbonitrile Chemical compound C1=CC(OC)=CC=C1N1C(C(=O)N(C=2C=CC(Br)=CC=2)C(C)=N2)=C2C(C#N)=N1 KKEGOCWGBQYACU-UHFFFAOYSA-N 0.000 claims 1
- IJTHFBCLFXAOPE-UHFFFAOYSA-N 7-methoxy-3-(4-methoxyphenyl)-1-methyl-5-phenylquinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CN(C)C2=CC(OC)=CC(C=3C=CC=CC=3)=C2C1=O IJTHFBCLFXAOPE-UHFFFAOYSA-N 0.000 claims 1
- NCRARSRDKAWCRJ-UHFFFAOYSA-N 8-chloro-1-methyl-4-oxo-5-phenylquinoline-3-carboxylic acid Chemical compound C1=CC(Cl)=C2N(C)C=C(C(O)=O)C(=O)C2=C1C1=CC=CC=C1 NCRARSRDKAWCRJ-UHFFFAOYSA-N 0.000 claims 1
- MAJMMGLCOTVPRC-UHFFFAOYSA-N 8-methoxy-3-(4-methoxyphenyl)-1-methyl-5-phenylquinolin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CN(C)C2=C(OC)C=CC(C=3C=CC=CC=3)=C2C1=O MAJMMGLCOTVPRC-UHFFFAOYSA-N 0.000 claims 1
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 claims 1
- 101800000414 Corticotropin Proteins 0.000 claims 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N Methyl benzoate Natural products COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims 1
- 102100027467 Pro-opiomelanocortin Human genes 0.000 claims 1
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims 1
- 239000005557 antagonist Substances 0.000 claims 1
- 150000001721 carbon Chemical class 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 claims 1
- 229960000258 corticotropin Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 229940095102 methyl benzoate Drugs 0.000 claims 1
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 1
- 239000003488 releasing hormone Substances 0.000 claims 1
- 125000005415 substituted alkoxy group Chemical group 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- 125000003107 substituted aryl group Chemical group 0.000 claims 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims 1
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 57
- 239000000243 solution Substances 0.000 description 49
- 238000006243 chemical reaction Methods 0.000 description 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 239000000203 mixture Substances 0.000 description 22
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 238000003818 flash chromatography Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- 125000003342 alkenyl group Chemical group 0.000 description 9
- 125000003545 alkoxy group Chemical group 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 9
- 235000019341 magnesium sulphate Nutrition 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 6
- 125000000304 alkynyl group Chemical group 0.000 description 6
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- 239000000284 extract Substances 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 description 5
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 150000002148 esters Chemical class 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 4
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
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- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 229930185107 quinolinone Natural products 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- PNGLEYLFMHGIQO-UHFFFAOYSA-M sodium;3-(n-ethyl-3-methoxyanilino)-2-hydroxypropane-1-sulfonate;dihydrate Chemical compound O.O.[Na+].[O-]S(=O)(=O)CC(O)CN(CC)C1=CC=CC(OC)=C1 PNGLEYLFMHGIQO-UHFFFAOYSA-M 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N valeric aldehyde Natural products CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
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| Application Number | Priority Date | Filing Date | Title |
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| US56028604P | 2004-04-07 | 2004-04-07 | |
| US60/560,286 | 2004-04-07 | ||
| PCT/US2005/013583 WO2005099688A2 (en) | 2004-04-07 | 2005-04-06 | Cyclic compounds |
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| Publication Number | Publication Date |
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| JP2007532580A JP2007532580A (ja) | 2007-11-15 |
| JP2007532580A5 true JP2007532580A5 (enExample) | 2008-05-08 |
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| EP (2) | EP1732541A4 (enExample) |
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| WO (1) | WO2005099688A2 (enExample) |
Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI360539B (en) | 2004-10-28 | 2012-03-21 | Shionogi & Co | 3-carbamoyl-2-pyridone derivatives |
| KR20080023680A (ko) | 2005-05-10 | 2008-03-14 | 인터뮨, 인크. | 스트레스-활성화 단백질 키나제 시스템을 조절하기 위한피리돈 유도체 |
| DE602006015851D1 (de) * | 2005-12-05 | 2010-09-09 | Merck Sharp & Dohme | Positive allosterische chinolon-m1-rezeptormodulatoren |
| CA2651817A1 (en) | 2006-05-11 | 2007-11-22 | Janssen Pharmaceutica N.V. | 3,4-dihydro-2h-benzo[1,4]oxazine and thiazine derivatives as cetp inhibitors |
| EP2088861A4 (en) | 2006-10-25 | 2010-07-07 | Takeda Pharmaceutical | Benzimidazole compounds |
| EP2125753A1 (en) | 2006-12-29 | 2009-12-02 | Takeda Pharmaceutical Company Limited | Fused heterocyclic compounds having crf antagonistic activity |
| BRPI0907230A2 (pt) * | 2008-01-22 | 2019-09-24 | Takeda Pharmaceuticals Co | composto, prodroga do composto, fármaco, método para tratar ou prevenir uma doença associada com as funções de um receptor de crf, e, uso do composto |
| EP2244577B1 (en) | 2008-01-25 | 2012-10-31 | Merck Sharp & Dohme Corp. | Quinolizidinone m1 receptor positive allosteric modulators |
| EP2296653B1 (en) | 2008-06-03 | 2016-01-27 | Intermune, Inc. | Compounds and methods for treating inflammatory and fibrotic disorders |
| US8220787B2 (en) * | 2008-09-19 | 2012-07-17 | Panasonic Corporation | Part mounting device |
| WO2010111626A2 (en) * | 2009-03-27 | 2010-09-30 | Takeda Pharmaceutical Company Limited | Poly (adp-ribose) polymerase (parp) inhibitors |
| CN101654435B (zh) * | 2009-06-09 | 2014-01-29 | 沈阳药科大学 | N-苯甲基喹啉羧酸类化合物、组合物及其制备方法 |
| EP2571361A4 (en) | 2010-05-19 | 2013-11-13 | Univ North Carolina | PYRAZOLOPYRIMIDINE COMPOUNDS FOR CANCER TREATMENT |
| US8362023B2 (en) | 2011-01-19 | 2013-01-29 | Hoffmann-La Roche Inc. | Pyrazolo pyrimidines |
| US11466017B2 (en) | 2011-03-10 | 2022-10-11 | Board Of Regents, The University Of Texas System | Heterocyclic inhibitors of PTPN11 |
| KR102063098B1 (ko) * | 2011-10-03 | 2020-01-08 | 더 유니버시티 오브 노쓰 캐롤라이나 엣 채플 힐 | 암 치료를 위한 피롤로피리미딘 화합물 |
| CN102492004A (zh) * | 2011-11-28 | 2012-06-13 | 四川大学 | 2-(4-β-D-吡喃阿洛糖苷-苯基)-2,3-二氢喹啉-4(1H)和2-(4-(2,3,4,6-四苄基)-β-D-吡喃阿洛糖苷-苯基)-2,3-二氢苯并吡喃制备方法和应用 |
| MX2014011115A (es) | 2012-03-16 | 2015-03-13 | Axikin Pharmaceuticals Inc | Inhibidores de 3,5-diaminopirazol cinasa. |
| CN104302627A (zh) | 2012-05-22 | 2015-01-21 | 北卡罗来纳大学教堂山分校 | 用于治疗癌症的嘧啶化合物 |
| AR092742A1 (es) | 2012-10-02 | 2015-04-29 | Intermune Inc | Piridinonas antifibroticas |
| WO2014062774A1 (en) | 2012-10-17 | 2014-04-24 | The University Of North Carolina At Chapel Hill | Pyrazolopyrimidine compounds for the treatment of cancer |
| EP2925752A4 (en) | 2012-11-27 | 2016-06-01 | Univ North Carolina | PYRIMIDINE COMPOUNDS FOR CANCER TREATMENT |
| CN105142635B (zh) | 2013-03-15 | 2021-07-27 | 艾匹根生物技术有限公司 | 有用于治疗疾病的杂环化合物 |
| EP3019502B1 (en) | 2013-07-08 | 2017-05-17 | Incyte Holdings Corporation | Tricyclic heterocycles as bet protein inhibitors |
| EA037949B1 (ru) | 2013-09-12 | 2021-06-10 | Янссен Байофарма, Инк. | Азапиридоновые соединения и их применение |
| TW201605812A (zh) | 2013-09-16 | 2016-02-16 | 拜耳製藥股份有限公司 | 經雙取代之三氟甲基嘧啶酮類及其用途 |
| NZ631142A (en) | 2013-09-18 | 2016-03-31 | Axikin Pharmaceuticals Inc | Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors |
| NZ720004A (en) * | 2013-11-18 | 2020-03-27 | Forma Therapeutics Inc | Tetrahydroquinoline compositions as bet bromodomain inhibitors |
| CN106029076B (zh) | 2013-11-18 | 2019-06-07 | 福马疗法公司 | 作为bet溴域抑制剂的苯并哌嗪组合物 |
| US9399640B2 (en) | 2013-11-26 | 2016-07-26 | Incyte Corporation | Substituted pyrrolo[2,3-c]pyridines and pyrazolo[3,4-c]pyridines as BET protein inhibitors |
| WO2015081189A1 (en) | 2013-11-26 | 2015-06-04 | Incyte Corporation | Bicyclic heterocycles as bet protein inhibitors |
| WO2015095492A1 (en) | 2013-12-19 | 2015-06-25 | Incyte Corporation | Tricyclic heterocycles as bet protein inhibitors |
| JP6525437B2 (ja) | 2014-04-02 | 2019-06-05 | インターミューン， インコーポレイテッド | 抗線維性ピリジノン |
| WO2015157123A1 (en) | 2014-04-11 | 2015-10-15 | The University Of North Carolina At Chapel Hill | Mertk-specific pyrrolopyrimidine compounds |
| KR102702503B1 (ko) | 2014-04-23 | 2024-09-05 | 인사이트 홀딩스 코포레이션 | BET 단백질의 저해제로서의 1H-피롤로[2,3-c]피리딘-7(6H)-온 및 피라졸로[3,4-c]피리딘-7(6H)-온 |
| WO2016036954A1 (en) * | 2014-09-05 | 2016-03-10 | Genentech, Inc. | Phthalazine derivatives of formula (i) as pcaf and gcn5 inhibitors for use in the treatment of cancer |
| WO2016044130A1 (en) | 2014-09-15 | 2016-03-24 | Incyte Corporation | Tricyclic heterocycles for use as bet protein inhibitors |
| MY191736A (en) | 2014-12-23 | 2022-07-13 | Axikin Pharmaceuticals Inc | 3,5-diaminopyrazole kinase inhibitors |
| EP3268368A4 (en) | 2015-03-11 | 2018-11-14 | Alios Biopharma, Inc. | Aza-pyridone compounds and uses thereof |
| DE102015012049A1 (de) * | 2015-09-15 | 2017-03-16 | Merck Patent Gmbh | Verbindungen als ASIC-Inhibitoren und deren Verwendungen |
| US20170121347A1 (en) | 2015-10-29 | 2017-05-04 | Incyte Corporation | Amorphous solid form of a bet protein inhibitor |
| WO2017156397A1 (en) * | 2016-03-11 | 2017-09-14 | Board Of Regents, The University Of Texas Sysytem | Heterocyclic inhibitors of ptpn11 |
| US10709708B2 (en) | 2016-03-17 | 2020-07-14 | The University Of North Carolina At Chapel Hill | Method of treating cancer with a combination of MER tyrosine kinase inhibitor and an epidermal growth factor receptor (EGFR) inhibitor |
| WO2017210134A1 (en) | 2016-05-31 | 2017-12-07 | Board Of Regents, University Of Texas System | Heterocyclic inhibitors of ptpn11 |
| PH12021551886A1 (en) | 2016-06-20 | 2023-07-17 | Incyte Corp | Crystalline solid forms of a bet inhibitor |
| KR101882790B1 (ko) | 2017-04-10 | 2018-08-24 | 한양대학교 산학협력단 | Dusp1 저해제를 함유하는 약제학적 조성물 |
| CN107382897B (zh) * | 2017-07-10 | 2021-05-04 | 浙江宏元药业股份有限公司 | 一种贝曲西班的中间体及其制备方法和应用 |
| CN111132973A (zh) | 2017-07-18 | 2020-05-08 | 拜耳作物科学股份公司 | 取代的3-杂芳氧基-1h-吡唑及其盐及其作为除草活性物质的用途 |
| TWI795440B (zh) | 2017-09-15 | 2023-03-11 | 美商佛瑪治療公司 | 作為ＣＢＰ／ｐ３００抑制劑之四氫─咪唑並喹啉化合物 |
| JP7326305B2 (ja) | 2018-03-02 | 2023-08-15 | 大塚製薬株式会社 | 医薬化合物 |
| CN112074505B (zh) | 2018-03-08 | 2024-04-05 | 因赛特公司 | 作为PI3K-γ抑制剂的氨基吡嗪二醇化合物 |
| EP3787627A4 (en) | 2018-05-02 | 2021-12-01 | Navire Pharma, Inc. | SUBSTITUTED HETEROCYCLIC INHIBITORS FOR PTPN11 |
| BR112020026783A2 (pt) | 2018-06-29 | 2021-03-30 | Forma Therapeutics, Inc. | Inibição da proteína de ligação creb (cbp) |
| US11046658B2 (en) | 2018-07-02 | 2021-06-29 | Incyte Corporation | Aminopyrazine derivatives as PI3K-γ inhibitors |
| EP3827009A4 (en) | 2018-07-24 | 2022-04-27 | Taiho Pharmaceutical Co., Ltd. | HETEROBICYCLIC COMPOUNDS TO INHIBIT SHP2 ACTIVITY |
| BR112021002327A2 (pt) | 2018-08-10 | 2021-05-04 | Navire Pharma, Inc. | derivados de 6-(4-amino-3-metil-2-oxa-8-azaespiro[4,5]decan-8-il)-3-(2,3-diclorofenil)-2-metilpirimidin-4(3h)-ona e compostos relacionados como inibidores de ptpn11(shp2) para o tratamento do câncer |
| US20200115389A1 (en) | 2018-09-18 | 2020-04-16 | Nikang Therapeutics, Inc. | Fused tricyclic ring derivatives as src homology-2 phosphatase inhibitors |
| EP3937940A4 (en) | 2019-03-15 | 2022-12-21 | Forma Therapeutics, Inc. | Inhibiting cyclic amp-responsive element-binding protein (creb) |
| GB201911928D0 (en) | 2019-08-20 | 2019-10-02 | Otsuka Pharma Co Ltd | Pharmaceutical compounds |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
| US11801243B2 (en) | 2020-09-23 | 2023-10-31 | Forma Therapeutics, Inc. | Bromodomain inhibitors for androgen receptor-driven cancers |
| US11795168B2 (en) | 2020-09-23 | 2023-10-24 | Forma Therapeutics, Inc. | Inhibiting cyclic amp-responsive element-binding protein (CREB) binding protein (CBP) |
| CN114181076A (zh) * | 2021-12-23 | 2022-03-15 | 维思普新材料（苏州）有限公司 | 一种2,6-二卤代苯甲酸甲酯的制备方法 |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0164204A1 (en) | 1984-05-12 | 1985-12-11 | FISONS plc | Novel pharmaceutically useful pyrimidines |
| NZ222843A (en) | 1986-12-22 | 1989-10-27 | Ortho Pharma Corp | Benzoxazinyl- and benzothiazinyl-tetrahydropyridazinones and intermediates, and medicaments |
| DE3711193A1 (de) | 1987-04-02 | 1988-10-13 | Bayer Ag | 5-substituierte chinolon- und naphthyridoncarbonsaeure-derivate |
| DE68917024D1 (de) | 1988-05-24 | 1994-09-01 | Kirin Brewery | 4(1H)-Chinolonderivate. |
| FR2662000A1 (fr) | 1990-05-11 | 1991-11-15 | Philips Composants | Carte a microcircuit. |
| WO1995016677A1 (en) | 1993-12-16 | 1995-06-22 | Nkk Corporation | Novel pyrimidine derivative and medicinal composition |
| US5656629A (en) | 1995-03-10 | 1997-08-12 | Sanofi Winthrop, Inc. | 6-substituted pyrazolo (3,4-d)pyrimidin-4-ones and compositions and methods of use thereof |
| EP0778277B1 (en) * | 1995-12-08 | 2003-06-25 | Pfizer Inc. | Substituted heterocyclic derivatives as CRF antagonists |
| SK14099A3 (en) * | 1996-08-06 | 2000-05-16 | Pfizer | Substituted pyrido- or pyrimido-containing 6,6- or 6,7-bicyclic derivatives |
| AR038955A1 (es) * | 1996-12-05 | 2005-02-02 | Amgen Inc | Compuestos de pirimidinona y piridona sustituidos y metodos para su uso |
| CZ299633B6 (cs) * | 1997-04-25 | 2008-09-24 | Pfizer Inc. | Pyrazolopyrimidinony, meziprodukty pro jejich výrobu a farmaceutické a veterinární kompozice na jejich bázi |
| US6037340A (en) | 1997-05-28 | 2000-03-14 | Cadus Pharmaceutical Corporation | Synthesis and use of thiophene- and pyrrole-based heteroaromatic compounds |
| IT1300056B1 (it) | 1998-04-17 | 2000-04-05 | Boehringer Ingelheim Italia | Eterocicli con anello a 6 termini difenil-sostituiti loro procedimento di preparazione e loro impiego come farmaci |
| AU4225499A (en) | 1998-06-03 | 1999-12-20 | Merck & Co., Inc. | Hiv integrase inhibitors |
| DE10021568A1 (de) | 1999-05-05 | 2000-11-09 | Novartis Ag | Neue Herbizide |
| FR2797444B1 (fr) | 1999-08-13 | 2003-02-07 | Lafon Labor | Compositions pharmaceutiques comprenant des 4-quinolones |
| KR100904011B1 (ko) | 2000-06-12 | 2009-06-22 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 1,2-디하이드로피리딘 화합물 및 그의 제조 방법 |
| FR2813791B1 (fr) | 2000-09-14 | 2004-03-12 | Lafon Labor | Utilisation de 2- et 4-quinolones pour inhiber la neo-proliferation intimale |
| ATE354573T1 (de) * | 2000-12-21 | 2007-03-15 | Vertex Pharma | ßPYRAZOLVERBINDUNGEN, DIE SICH ALS PROTEINKINASEINHIBITOREN EIGNENß |
| CN1630656A (zh) | 2001-02-02 | 2005-06-22 | 三菱制药株式会社 | 二氢吡唑并吡啶化合物及其制药用途 |
| WO2003005969A2 (en) * | 2001-07-12 | 2003-01-23 | Bristol-Myers Squibb Pharma Company | Tetrahydropurinones as corticotropin releasing factor |
| WO2003011293A2 (en) * | 2001-08-02 | 2003-02-13 | Neurocrine Biosciences, Inc. | Pyridinone and pyridazinone derivatives as gonadotropin-releasing hormone receptor antagonists |
| US20030071902A1 (en) | 2001-10-11 | 2003-04-17 | Allen Paul G. | System, devices, and methods for switching between video cameras |
| TWI330183B (enExample) * | 2001-10-22 | 2010-09-11 | Eisai R&D Man Co Ltd | |
| TWI301834B (en) | 2001-10-22 | 2008-10-11 | Eisai R&D Man Co Ltd | Pyrimidone compound and pharmaceutical composition including the same |
| AU2002340405A1 (en) * | 2001-11-20 | 2003-06-10 | Bristol-Myers Squibb Pharma Company | 3,7-dihydro-purine-2,6-dione derivatives as crf receptor ligands |
| GB0129260D0 (en) * | 2001-12-06 | 2002-01-23 | Eisai London Res Lab Ltd | Pharmaceutical compositions and their uses |
| ATE434610T1 (de) * | 2002-03-13 | 2009-07-15 | Euro Celtique Sa | Aryl substituierte pyrimidine und deren verwendung |
| JP2006510597A (ja) * | 2002-09-27 | 2006-03-30 | メルク エンド カムパニー インコーポレーテッド | 置換ピリミジン類 |
| US7030145B2 (en) | 2003-04-18 | 2006-04-18 | Bristol-Myers Squibb Company | Pyridinyl derivatives for the treatment of depression |
| US7112585B2 (en) | 2003-04-18 | 2006-09-26 | Bristol-Myers Squibb Company | Pyrimidine derivatives as corticotropin releasing factor inhibitors |
-
2005
- 2005-04-06 JP JP2007507576A patent/JP4790703B2/ja not_active Expired - Fee Related
- 2005-04-06 CA CA002562244A patent/CA2562244A1/en not_active Abandoned
- 2005-04-06 WO PCT/US2005/013583 patent/WO2005099688A2/en not_active Ceased
- 2005-04-06 US US10/593,891 patent/US7897607B2/en not_active Expired - Fee Related
- 2005-04-06 EP EP05741906A patent/EP1732541A4/en not_active Withdrawn
- 2005-04-06 EP EP12157517A patent/EP2522670A1/en not_active Withdrawn
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