JP5730281B2 - ポリ(adp−リボース)ポリメラーゼ(parp)阻害剤 - Google Patents
ポリ(adp−リボース)ポリメラーゼ(parp)阻害剤 Download PDFInfo
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- JP5730281B2 JP5730281B2 JP2012502295A JP2012502295A JP5730281B2 JP 5730281 B2 JP5730281 B2 JP 5730281B2 JP 2012502295 A JP2012502295 A JP 2012502295A JP 2012502295 A JP2012502295 A JP 2012502295A JP 5730281 B2 JP5730281 B2 JP 5730281B2
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- JP
- Japan
- Prior art keywords
- methyl
- benzo
- oxazin
- oxo
- dihydro
- 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.)
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- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 title description 56
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 title description 56
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 title description 54
- 239000003112 inhibitor Substances 0.000 title description 22
- 150000001875 compounds Chemical class 0.000 claims description 356
- 125000005842 heteroatom Chemical group 0.000 claims description 311
- 125000000217 alkyl group Chemical group 0.000 claims description 181
- -1 4-((8-methoxy-2-methyl-3-oxo-3,4-dihydro-2H-benzo [b] [1,4] oxazin-6-yl) methyl) piperazin-1-yl Chemical group 0.000 claims description 161
- 125000003118 aryl group Chemical group 0.000 claims description 151
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 128
- 239000001257 hydrogen Substances 0.000 claims description 86
- 229910052739 hydrogen Inorganic materials 0.000 claims description 86
- 150000003839 salts Chemical class 0.000 claims description 56
- 125000001424 substituent group Chemical group 0.000 claims description 50
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 42
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 40
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 38
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 37
- 239000003814 drug Substances 0.000 claims description 31
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 31
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims description 28
- 150000001408 amides Chemical class 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N Benzoic acid Natural products OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- PFEWYNQWEUWTKM-OAHLLOKOSA-N (2r)-2-methyl-6-[(4-phenylpiperidin-1-yl)methyl]-4h-1,4-benzoxazin-3-one Chemical compound O([C@@H](C(NC1=C2)=O)C)C1=CC=C2CN(CC1)CCC1C1=CC=CC=C1 PFEWYNQWEUWTKM-OAHLLOKOSA-N 0.000 claims description 3
- UXKGKMDPTXLNNA-CQSZACIVSA-N (2r)-6-[[4-(4-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound O([C@@H](C(NC1=C2)=O)C)C1=CC=C2CN(CC=1)CCC=1C1=CC=C(Cl)C=C1 UXKGKMDPTXLNNA-CQSZACIVSA-N 0.000 claims description 3
- PFEWYNQWEUWTKM-HNNXBMFYSA-N (2s)-2-methyl-6-[(4-phenylpiperidin-1-yl)methyl]-4h-1,4-benzoxazin-3-one Chemical compound O([C@H](C(NC1=C2)=O)C)C1=CC=C2CN(CC1)CCC1C1=CC=CC=C1 PFEWYNQWEUWTKM-HNNXBMFYSA-N 0.000 claims description 3
- UXKGKMDPTXLNNA-AWEZNQCLSA-N (2s)-6-[[4-(4-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound O([C@H](C(NC1=C2)=O)C)C1=CC=C2CN(CC=1)CCC=1C1=CC=C(Cl)C=C1 UXKGKMDPTXLNNA-AWEZNQCLSA-N 0.000 claims description 3
- VOTOMUXJSSQBOB-UHFFFAOYSA-N 1,3,7-trimethyl-8-[4-[(2-methyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]purine-2,6-dione Chemical compound CN1C(=O)N(C)C(=O)C(N2C)=C1N=C2N(CC1)CCN1CC1=CC=C2OC(C)C(=O)NC2=C1 VOTOMUXJSSQBOB-UHFFFAOYSA-N 0.000 claims description 3
- DYTZPQZXOZOYCN-UHFFFAOYSA-N 2-methyl-6-(4-phenylpiperidin-1-yl)sulfonyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1S(=O)(=O)N(CC1)CCC1C1=CC=CC=C1 DYTZPQZXOZOYCN-UHFFFAOYSA-N 0.000 claims description 3
- HKXRGSMSGJKEQM-UHFFFAOYSA-N 2-methyl-6-[(3-oxo-4-phenylpiperazin-1-yl)methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1=O)CCN1C1=CC=CC=C1 HKXRGSMSGJKEQM-UHFFFAOYSA-N 0.000 claims description 3
- QWIAEWJWOQPVDM-UHFFFAOYSA-N 2-methyl-6-[(4-phenyl-3,6-dihydro-2h-pyridin-1-yl)methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC=1)CCC=1C1=CC=CC=C1 QWIAEWJWOQPVDM-UHFFFAOYSA-N 0.000 claims description 3
- WCWRIBRJBBSZHM-UHFFFAOYSA-N 2-methyl-6-[(4-phenylpiperazin-1-yl)methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=CC=C1 WCWRIBRJBBSZHM-UHFFFAOYSA-N 0.000 claims description 3
- PFEWYNQWEUWTKM-UHFFFAOYSA-N 2-methyl-6-[(4-phenylpiperidin-1-yl)methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCC1C1=CC=CC=C1 PFEWYNQWEUWTKM-UHFFFAOYSA-N 0.000 claims description 3
- TZXSSOIEBYRMJR-UHFFFAOYSA-N 2-methyl-6-[[4-(2-methylphenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=CC=C1C TZXSSOIEBYRMJR-UHFFFAOYSA-N 0.000 claims description 3
- UMMYKRPKLYPLBH-UHFFFAOYSA-N 2-methyl-6-[[4-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C(SN=1)=NC=1C1=CC=CC=C1 UMMYKRPKLYPLBH-UHFFFAOYSA-N 0.000 claims description 3
- RDIKZADOVAERSY-UHFFFAOYSA-N 2-methyl-6-[[4-(4-methylphenyl)piperidin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCC1C1=CC=C(C)C=C1 RDIKZADOVAERSY-UHFFFAOYSA-N 0.000 claims description 3
- BBDIQRAUTLIFAU-UHFFFAOYSA-N 2-methyl-6-[[4-(4-nitrophenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=C([N+]([O-])=O)C=C1 BBDIQRAUTLIFAU-UHFFFAOYSA-N 0.000 claims description 3
- JRVISWMEHQYAIZ-UHFFFAOYSA-N 6-[(4-cycloheptylpiperazin-1-yl)methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1CCCCCC1 JRVISWMEHQYAIZ-UHFFFAOYSA-N 0.000 claims description 3
- UUPVWYOCGKDEQA-UHFFFAOYSA-N 6-[(4-cyclopentylpiperazin-1-yl)methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1CCCC1 UUPVWYOCGKDEQA-UHFFFAOYSA-N 0.000 claims description 3
- IHTQVOGLEPUBGN-UHFFFAOYSA-N 6-[[4-(1h-benzimidazol-2-yl)piperazin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=CC=C2NC(N3CCN(CC3)CC3=CC=C4OC(C(NC4=C3)=O)C)=NC2=C1 IHTQVOGLEPUBGN-UHFFFAOYSA-N 0.000 claims description 3
- IVWRBJFTJRHXJZ-UHFFFAOYSA-N 6-[[4-(1h-benzimidazol-2-yl)piperidin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=CC=C2NC(C3CCN(CC3)CC3=CC=C4OC(C(NC4=C3)=O)C)=NC2=C1 IVWRBJFTJRHXJZ-UHFFFAOYSA-N 0.000 claims description 3
- FGKQSOCXZPPSHA-UHFFFAOYSA-N 6-[[4-(2-hydroxyphenyl)piperazin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=CC=C1O FGKQSOCXZPPSHA-UHFFFAOYSA-N 0.000 claims description 3
- NXKRCHXQFPSXEI-UHFFFAOYSA-N 6-[[4-(2-methoxyphenyl)piperazin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound COC1=CC=CC=C1N1CCN(CC=2C=C3NC(=O)C(C)OC3=CC=2)CC1 NXKRCHXQFPSXEI-UHFFFAOYSA-N 0.000 claims description 3
- KDCBBDVOCNKBOP-UHFFFAOYSA-N 6-[[4-(4-aminophenyl)piperazin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=C(N)C=C1 KDCBBDVOCNKBOP-UHFFFAOYSA-N 0.000 claims description 3
- UXKGKMDPTXLNNA-UHFFFAOYSA-N 6-[[4-(4-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC=1)CCC=1C1=CC=C(Cl)C=C1 UXKGKMDPTXLNNA-UHFFFAOYSA-N 0.000 claims description 3
- XLLVHHTXJKJVDK-UHFFFAOYSA-N 6-[[4-(4-chlorophenyl)piperidin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCC1C1=CC=C(Cl)C=C1 XLLVHHTXJKJVDK-UHFFFAOYSA-N 0.000 claims description 3
- SHJJLQSSKCGDGL-UHFFFAOYSA-N 6-[[4-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC=1)CCC=1C1=CC=C(F)C=C1 SHJJLQSSKCGDGL-UHFFFAOYSA-N 0.000 claims description 3
- OAOCNSHPLQKZJM-UHFFFAOYSA-N 6-[[4-(4-fluorophenyl)piperidin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCC1C1=CC=C(F)C=C1 OAOCNSHPLQKZJM-UHFFFAOYSA-N 0.000 claims description 3
- JGOGGUHIIKHFJF-UHFFFAOYSA-N 7-chloro-2-methyl-6-[(4-phenylpiperazin-1-yl)methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC(Cl)=C1CN(CC1)CCN1C1=CC=CC=C1 JGOGGUHIIKHFJF-UHFFFAOYSA-N 0.000 claims description 3
- 239000005711 Benzoic acid Substances 0.000 claims description 3
- 235000010233 benzoic acid Nutrition 0.000 claims description 3
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- OYTPPOHVHOLFCC-UHFFFAOYSA-N 4-[4-[(2-methyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]benzoic acid Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=C(C(O)=O)C=C1 OYTPPOHVHOLFCC-UHFFFAOYSA-N 0.000 claims description 2
- BCUZJWLXPTXDQU-UHFFFAOYSA-N 6-[[4-(5-chloropyridin-2-yl)piperazin-1-yl]methyl]-2-methyl-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=C(Cl)C=N1 BCUZJWLXPTXDQU-UHFFFAOYSA-N 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 9
- 125000001475 halogen functional group Chemical group 0.000 claims 6
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 2
- HDJPUGCLTLLNPO-UHFFFAOYSA-N 2-methyl-6-[[4-(4-methylsulfonylphenyl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=C(S(C)(=O)=O)C=C1 HDJPUGCLTLLNPO-UHFFFAOYSA-N 0.000 claims 1
- MKDPOFXLNTZGKB-UHFFFAOYSA-N 2-methyl-6-[[4-(5-methylpyridin-2-yl)piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=C(C)C=N1 MKDPOFXLNTZGKB-UHFFFAOYSA-N 0.000 claims 1
- FYZCNXREGOJZRF-UHFFFAOYSA-N 2-methyl-6-[[4-[3-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=CC(C(F)(F)F)=C1 FYZCNXREGOJZRF-UHFFFAOYSA-N 0.000 claims 1
- HKWBGRSNTXJPGQ-UHFFFAOYSA-N 2-methyl-6-[[4-[4-(pyrrolidine-1-carbonyl)phenyl]piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C(C=C1)=CC=C1C(=O)N1CCCC1 HKWBGRSNTXJPGQ-UHFFFAOYSA-N 0.000 claims 1
- RKBSUFHPSGWMSY-UHFFFAOYSA-N 2-methyl-6-[[4-[4-(trifluoromethyl)phenyl]piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=C(C(F)(F)F)C=C1 RKBSUFHPSGWMSY-UHFFFAOYSA-N 0.000 claims 1
- IDACYAIDXOGILQ-UHFFFAOYSA-N 2-methyl-6-[[4-[4-(trifluoromethyl)phenyl]piperidin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCC1C1=CC=C(C(F)(F)F)C=C1 IDACYAIDXOGILQ-UHFFFAOYSA-N 0.000 claims 1
- RGYCDTAGSAEFKT-UHFFFAOYSA-N 2-methyl-6-[[4-[5-(trifluoromethyl)pyridin-2-yl]piperazin-1-yl]methyl]-4h-1,4-benzoxazin-3-one Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCN1C1=CC=C(C(F)(F)F)C=N1 RGYCDTAGSAEFKT-UHFFFAOYSA-N 0.000 claims 1
- IWEWMCFHBJPZKC-UHFFFAOYSA-N 3-[1-[(2-methyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperidin-4-yl]benzoic acid Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCC1C1=CC=CC(C(O)=O)=C1 IWEWMCFHBJPZKC-UHFFFAOYSA-N 0.000 claims 1
- QCGWNEQSRDSVJS-UHFFFAOYSA-N 3-chloro-4-[4-[(2,8-dimethyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]-n-ethylbenzamide Chemical compound ClC1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C3NC(=O)C(C)OC3=C(C)C=2)CC1 QCGWNEQSRDSVJS-UHFFFAOYSA-N 0.000 claims 1
- VGVJZUWQVBBTHR-UHFFFAOYSA-N 3-chloro-4-[4-[(2,8-dimethyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]-n-methylbenzamide Chemical compound ClC1=CC(C(=O)NC)=CC=C1N1CCN(CC=2C=C3NC(=O)C(C)OC3=C(C)C=2)CC1 VGVJZUWQVBBTHR-UHFFFAOYSA-N 0.000 claims 1
- DZTSKWQJDLWCBV-UHFFFAOYSA-N 3-chloro-4-[4-[(8-ethoxy-2-methyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]-n-ethylbenzamide Chemical compound ClC1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C(OCC)C=3OC(C)C(=O)NC=3C=2)CC1 DZTSKWQJDLWCBV-UHFFFAOYSA-N 0.000 claims 1
- WZLMKZAOAWAKHE-UHFFFAOYSA-N 3-chloro-4-[4-[(8-methoxy-2-methyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]-n-methylbenzamide Chemical compound ClC1=CC(C(=O)NC)=CC=C1N1CCN(CC=2C=C(OC)C=3OC(C)C(=O)NC=3C=2)CC1 WZLMKZAOAWAKHE-UHFFFAOYSA-N 0.000 claims 1
- KFACVCOTRXSGCH-UHFFFAOYSA-N 3-chloro-4-[4-[[8-(difluoromethoxy)-2-methyl-3-oxo-4h-1,4-benzoxazin-6-yl]methyl]piperazin-1-yl]-n-ethylbenzamide Chemical compound ClC1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C(OC(F)F)C=3OC(C)C(=O)NC=3C=2)CC1 KFACVCOTRXSGCH-UHFFFAOYSA-N 0.000 claims 1
- DPAHEKNEXYTGDV-UHFFFAOYSA-N 3-fluoro-4-[4-[(8-methoxy-2-methyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]-n-methylbenzamide Chemical compound FC1=CC(C(=O)NC)=CC=C1N1CCN(CC=2C=C(OC)C=3OC(C)C(=O)NC=3C=2)CC1 DPAHEKNEXYTGDV-UHFFFAOYSA-N 0.000 claims 1
- BGGAXINXZXGLTH-UHFFFAOYSA-N 4-[1-[(2-methyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperidin-4-yl]benzoic acid Chemical compound C1=C2NC(=O)C(C)OC2=CC=C1CN(CC1)CCC1C1=CC=C(C(O)=O)C=C1 BGGAXINXZXGLTH-UHFFFAOYSA-N 0.000 claims 1
- WGYCTLCBZOGBLH-UHFFFAOYSA-N 4-[4-[(2,8-dimethyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]-3-fluoro-n-methylbenzamide Chemical compound FC1=CC(C(=O)NC)=CC=C1N1CCN(CC=2C=C3NC(=O)C(C)OC3=C(C)C=2)CC1 WGYCTLCBZOGBLH-UHFFFAOYSA-N 0.000 claims 1
- VSEUBTHLHOCRIW-UHFFFAOYSA-N 4-[4-[(2,8-dimethyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]-n,3-dimethylbenzamide Chemical compound CC1=CC(C(=O)NC)=CC=C1N1CCN(CC=2C=C3NC(=O)C(C)OC3=C(C)C=2)CC1 VSEUBTHLHOCRIW-UHFFFAOYSA-N 0.000 claims 1
- INKHOZMJLWCMKZ-UHFFFAOYSA-N 4-[4-[(2,8-dimethyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]-n-ethyl-3-fluorobenzamide Chemical compound FC1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C3NC(=O)C(C)OC3=C(C)C=2)CC1 INKHOZMJLWCMKZ-UHFFFAOYSA-N 0.000 claims 1
- NDPXSBJMMOJZHP-UHFFFAOYSA-N 4-[4-[(2,8-dimethyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]-n-ethyl-3-methylbenzamide Chemical compound CC1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C3NC(=O)C(C)OC3=C(C)C=2)CC1 NDPXSBJMMOJZHP-UHFFFAOYSA-N 0.000 claims 1
- JOXGAKHVVVHYRB-UHFFFAOYSA-N 4-[4-[(2,8-dimethyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]-n-ethylbenzamide Chemical compound C1=CC(C(=O)NCC)=CC=C1N1CCN(CC=2C=C3NC(=O)C(C)OC3=C(C)C=2)CC1 JOXGAKHVVVHYRB-UHFFFAOYSA-N 0.000 claims 1
- OYJQBDOBRMEDSI-UHFFFAOYSA-N 4-[4-[(2,8-dimethyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]-n-methylbenzamide Chemical compound C1=CC(C(=O)NC)=CC=C1N1CCN(CC=2C=C3NC(=O)C(C)OC3=C(C)C=2)CC1 OYJQBDOBRMEDSI-UHFFFAOYSA-N 0.000 claims 1
- BAHZHLVDQFLUSB-UHFFFAOYSA-N 4-[4-[(2,8-dimethyl-3-oxo-4h-1,4-benzoxazin-6-yl)methyl]piperazin-1-yl]benzonitrile Chemical compound C1=C2NC(=O)C(C)OC2=C(C)C=C1CN(CC1)CCN1C1=CC=C(C#N)C=C1 BAHZHLVDQFLUSB-UHFFFAOYSA-N 0.000 claims 1
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Applications Claiming Priority (3)
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| US16413209P | 2009-03-27 | 2009-03-27 | |
| US61/164,132 | 2009-03-27 | ||
| PCT/US2010/028878 WO2010111626A2 (en) | 2009-03-27 | 2010-03-26 | Poly (adp-ribose) polymerase (parp) inhibitors |
Publications (3)
| Publication Number | Publication Date |
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| JP2012522007A JP2012522007A (ja) | 2012-09-20 |
| JP2012522007A5 JP2012522007A5 (enExample) | 2013-05-16 |
| JP5730281B2 true JP5730281B2 (ja) | 2015-06-10 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| JP2012502295A Active JP5730281B2 (ja) | 2009-03-27 | 2010-03-26 | ポリ(adp−リボース)ポリメラーゼ(parp)阻害剤 |
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| Country | Link |
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| US (1) | US8669249B2 (enExample) |
| EP (1) | EP2415767B1 (enExample) |
| JP (1) | JP5730281B2 (enExample) |
| WO (1) | WO2010111626A2 (enExample) |
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| EA025322B1 (ru) | 2011-12-22 | 2016-12-30 | Новартис Аг | Производные дигидробензооксазина и дигидропиридооксазина |
| MX366703B (es) | 2013-03-15 | 2019-07-22 | Incyte Holdings Corp | Heterociclos tricíclicos como inhibidores de la proteína bet. |
| WO2014184272A2 (en) * | 2013-05-14 | 2014-11-20 | Medizinische Hochschule Hannover | Means and methods for treating cancer |
| WO2015006193A1 (en) | 2013-07-08 | 2015-01-15 | Incyte Corporation | Tricyclic heterocycles as bet protein inhibitors |
| 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 |
| US9309246B2 (en) | 2013-12-19 | 2016-04-12 | Incyte Corporation | Tricyclic heterocycles as BET protein inhibitors |
| SI3674302T1 (sl) | 2014-04-23 | 2023-07-31 | Incyte Holdings Corporation | 1h-pirolo(2,3-c)piridin-7(6h)-oni in pirazolo(3,4-c)piridin-7(6h)-oni kot zaviralci proteinov bet |
| ES2855225T3 (es) | 2014-09-15 | 2021-09-23 | Incyte Corp | Heterociclos tricíclicos para su uso como inhibidores de proteínas BET |
| EP3265560B1 (en) | 2015-03-02 | 2021-12-08 | Sinai Health System | Homologous recombination factors |
| US20170121347A1 (en) | 2015-10-29 | 2017-05-04 | Incyte Corporation | Amorphous solid form of a bet protein inhibitor |
| CR20190027A (es) | 2016-06-20 | 2019-05-16 | Incyte Corp | Formas sólidas cristalinas de un inhibidor de bet |
| EP3717477B1 (en) | 2017-11-28 | 2022-07-20 | F. Hoffmann-La Roche AG | New heterocyclic compounds |
| TW201930300A (zh) * | 2017-12-15 | 2019-08-01 | 瑞士商赫孚孟拉羅股份公司 | 新雜環化合物 |
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- 2010-03-26 US US13/260,680 patent/US8669249B2/en not_active Expired - Fee Related
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| JP2012522007A (ja) | 2012-09-20 |
| US8669249B2 (en) | 2014-03-11 |
| US20120094992A1 (en) | 2012-04-19 |
| EP2415767B1 (en) | 2014-09-03 |
| EP2415767A1 (en) | 2012-02-08 |
| WO2010111626A2 (en) | 2010-09-30 |
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