JP2019537571A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2019537571A5 JP2019537571A5 JP2019520588A JP2019520588A JP2019537571A5 JP 2019537571 A5 JP2019537571 A5 JP 2019537571A5 JP 2019520588 A JP2019520588 A JP 2019520588A JP 2019520588 A JP2019520588 A JP 2019520588A JP 2019537571 A5 JP2019537571 A5 JP 2019537571A5
- Authority
- JP
- Japan
- Prior art keywords
- dimethylisoxazole
- pyrrolidine
- benzo
- imidazol
- difluorophenyl
- 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
Links
- -1 3,5-dimethylisoxazole-4-yl Chemical group 0.000 claims 215
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims 83
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical group O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 claims 73
- XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical group O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims 25
- 150000001875 compounds Chemical class 0.000 claims 20
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims 15
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 12
- 206010028980 Neoplasm Diseases 0.000 claims 9
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 8
- 238000000034 method Methods 0.000 claims 8
- 201000011510 cancer Diseases 0.000 claims 7
- YPWFISCTZQNZAU-UHFFFAOYSA-N Thiane Chemical compound C1CCSCC1 YPWFISCTZQNZAU-UHFFFAOYSA-N 0.000 claims 5
- 125000003118 aryl group Chemical group 0.000 claims 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 125000001072 heteroaryl group Chemical group 0.000 claims 3
- 239000003112 inhibitor Substances 0.000 claims 3
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 229940124597 therapeutic agent Drugs 0.000 claims 3
- JXEHOLBKBUDBMX-OGDGHAERSA-N (5S)-1-(3,4-difluorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(2-hydroxypropyl)benzimidazol-2-yl]pyrrolidin-2-one Chemical compound CC(O)Cn1c(nc2cc(ccc12)-c1c(C)noc1C)[C@@H]1CCC(=O)N1c1ccc(F)c(F)c1 JXEHOLBKBUDBMX-OGDGHAERSA-N 0.000 claims 2
- REIBXPXUCPDXOM-XXBNENTESA-N (5S)-5-[1-[(1R)-3,3-difluorocyclopentyl]-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(3-fluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound FC1(C[C@@H](CC1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCC(N1C1=CC(=C(C=C1)OC)F)=O)F REIBXPXUCPDXOM-XXBNENTESA-N 0.000 claims 2
- OIJFMBYWYMOYGI-QPPBQGQZSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-[4-(trifluoromethyl)phenyl]pyrrolidin-2-one Chemical compound Cc1noc(C)c1-c1ccc2n([C@@H]3CCN(C3)S(C)(=O)=O)c(nc2c1)[C@@H]1CCC(=O)N1c1ccc(cc1)C(F)(F)F OIJFMBYWYMOYGI-QPPBQGQZSA-N 0.000 claims 2
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 claims 2
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 claims 2
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 claims 2
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims 2
- YFPCLQKFNXUAAK-UHFFFAOYSA-N cyclopentyl acetate Chemical compound CC(=O)OC1CCCC1 YFPCLQKFNXUAAK-UHFFFAOYSA-N 0.000 claims 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 125000000623 heterocyclic group Chemical group 0.000 claims 2
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 2
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- ZBIORFWTWOHVLU-ZJSXRUAMSA-N (5R)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(3-fluorophenyl)pyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)[C@H]2CCC(N2C2=CC(=CC=C2)F)=O)[C@H]2CN(CC2)S(=O)(=O)C)C=C1)C ZBIORFWTWOHVLU-ZJSXRUAMSA-N 0.000 claims 1
- BXMMBJZCICOLJZ-ZJSXRUAMSA-N (5R)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-phenylpyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)[C@H]2CCC(N2C2=CC=CC=C2)=O)[C@H]2CN(CC2)S(=O)(=O)C)C=C1)C BXMMBJZCICOLJZ-ZJSXRUAMSA-N 0.000 claims 1
- LSYSNZWPNDLMJT-VWLOTQADSA-N (5S)-1-(3,4-dichlorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(1-methylsulfonylpiperidin-4-yl)benzimidazol-2-yl]pyrrolidin-2-one Chemical compound ClC=1C=C(C=CC=1Cl)N1C(CC[C@H]1C1=NC2=C(N1C1CCN(CC1)S(=O)(=O)C)C=CC(=C2)C=1C(=NOC=1C)C)=O LSYSNZWPNDLMJT-VWLOTQADSA-N 0.000 claims 1
- JOSVVJCONODIKB-WNEJPSKBSA-N (5S)-1-(3,4-dichlorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(4-hydroxycyclohexyl)benzimidazol-2-yl]pyrrolidin-2-one Chemical compound Cc1noc(C)c1-c1ccc2n(C3CCC(O)CC3)c(nc2c1)[C@@H]1CCC(=O)N1c1ccc(Cl)c(Cl)c1 JOSVVJCONODIKB-WNEJPSKBSA-N 0.000 claims 1
- QQABZVCPNWWMAA-YJLYGGOZSA-N (5S)-1-(3,4-dichlorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(1R,3R)-3-hydroxycyclopentyl]benzimidazol-2-yl]pyrrolidin-2-one Chemical compound ClC=1C=C(C=CC=1Cl)N1C(CC[C@H]1C1=NC2=C(N1[C@H]1C[C@@H](CC1)O)C=CC(=C2)C=1C(=NOC=1C)C)=O QQABZVCPNWWMAA-YJLYGGOZSA-N 0.000 claims 1
- MIVMMBNMIRJOBR-QHCPKHFHSA-N (5S)-1-(3,4-difluorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(1,3-thiazol-4-ylmethyl)benzimidazol-2-yl]pyrrolidin-2-one Chemical compound Cc1noc(C)c1-c1ccc2n(Cc3cscn3)c(nc2c1)[C@@H]1CCC(=O)N1c1ccc(F)c(F)c1 MIVMMBNMIRJOBR-QHCPKHFHSA-N 0.000 claims 1
- BLJLQCZVQABBHU-WIIYFNMSSA-N (5S)-1-(3,4-difluorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(1-methylpyrrolidin-3-yl)benzimidazol-2-yl]pyrrolidin-2-one Chemical compound FC=1C=C(C=CC=1F)N1C(CC[C@H]1C1=NC2=C(N1C1CN(CC1)C)C=CC(=C2)C=1C(=NOC=1C)C)=O BLJLQCZVQABBHU-WIIYFNMSSA-N 0.000 claims 1
- STOMFPNBLULCGG-WFCDKWQMSA-N (5S)-1-(3,4-difluorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(2-methyloxan-4-yl)benzimidazol-2-yl]pyrrolidin-2-one Chemical compound FC=1C=C(C=CC=1F)N1C(CC[C@H]1C1=NC2=C(N1C1CC(OCC1)C)C=CC(=C2)C=1C(=NOC=1C)C)=O STOMFPNBLULCGG-WFCDKWQMSA-N 0.000 claims 1
- MGEBXIDSZOPBPD-QHCPKHFHSA-N (5S)-1-(3,4-difluorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(2-methylpropyl)benzimidazol-2-yl]pyrrolidin-2-one Chemical compound FC=1C=C(C=CC=1F)N1C(CC[C@H]1C1=NC2=C(N1CC(C)C)C=CC(=C2)C=1C(=NOC=1C)C)=O MGEBXIDSZOPBPD-QHCPKHFHSA-N 0.000 claims 1
- XDIXTBJESCLKOS-QHCPKHFHSA-N (5S)-1-(3,4-difluorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(3-methoxypropyl)benzimidazol-2-yl]pyrrolidin-2-one Chemical compound FC=1C=C(C=CC=1F)N1C(CC[C@H]1C1=NC2=C(N1CCCOC)C=CC(=C2)C=1C(=NOC=1C)C)=O XDIXTBJESCLKOS-QHCPKHFHSA-N 0.000 claims 1
- FBRULYOLFNZEHJ-QFIPXVFZSA-N (5S)-1-(3,4-difluorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-propylbenzimidazol-2-yl]pyrrolidin-2-one Chemical compound FC=1C=C(C=CC=1F)N1C(CC[C@H]1C1=NC2=C(N1CCC)C=CC(=C2)C=1C(=NOC=1C)C)=O FBRULYOLFNZEHJ-QFIPXVFZSA-N 0.000 claims 1
- ZXHMDXFSZLXPMZ-IBGZPJMESA-N (5S)-1-(3,4-difluorophenyl)-5-[6-(3,5-dimethyl-1,2-oxazol-4-yl)-1H-benzimidazol-2-yl]pyrrolidin-2-one Chemical compound FC=1C=C(C=CC=1F)N1C(CC[C@H]1C1=NC2=C(N1)C=CC(=C2)C=1C(=NOC=1C)C)=O ZXHMDXFSZLXPMZ-IBGZPJMESA-N 0.000 claims 1
- VUHJNIVODXDQQT-DEOSSOPVSA-N (5S)-1-(3-chloro-4-methoxyphenyl)-5-[1-(4,4-difluorocyclohexyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]pyrrolidin-2-one Chemical compound ClC=1C=C(C=CC=1OC)N1C(CC[C@H]1C1=NC2=C(N1C1CCC(CC1)(F)F)C=CC(=C2)C=1C(=NOC=1C)C)=O VUHJNIVODXDQQT-DEOSSOPVSA-N 0.000 claims 1
- FWMSYRJASDIZFN-FPGHNAPASA-N (5S)-1-(3-chloro-4-methoxyphenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(1R,3R)-3-hydroxycyclopentyl]benzimidazol-2-yl]pyrrolidin-2-one Chemical compound ClC=1C=C(C=CC=1OC)N1C(CC[C@H]1C1=NC2=C(N1[C@H]1C[C@@H](CC1)O)C=CC(=C2)C=1C(=NOC=1C)C)=O FWMSYRJASDIZFN-FPGHNAPASA-N 0.000 claims 1
- WIOLKUXVELQOCK-YKSBVNFPSA-N (5S)-1-(3-chloro-4-methoxyphenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]pyrrolidin-2-one Chemical compound ClC=1C=C(C=CC=1OC)N1C(CC[C@H]1C1=NC2=C(N1[C@H]1CN(CC1)S(=O)(=O)C)C=CC(=C2)C=1C(=NOC=1C)C)=O WIOLKUXVELQOCK-YKSBVNFPSA-N 0.000 claims 1
- STKUXGVVJSZLQW-WIIYFNMSSA-N (5S)-1-(4-chloro-3-fluorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(1-methylpyrrolidin-3-yl)benzimidazol-2-yl]pyrrolidin-2-one Chemical compound ClC1=C(C=C(C=C1)N1C(CC[C@H]1C1=NC2=C(N1C1CN(CC1)C)C=CC(=C2)C=1C(=NOC=1C)C)=O)F STKUXGVVJSZLQW-WIIYFNMSSA-N 0.000 claims 1
- JSLICXNQLYEHPA-YJLYGGOZSA-N (5S)-1-(4-chloro-3-fluorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(1R,3R)-3-hydroxycyclopentyl]benzimidazol-2-yl]pyrrolidin-2-one Chemical compound Cc1noc(C)c1-c1ccc2n([C@@H]3CC[C@@H](O)C3)c(nc2c1)[C@@H]1CCC(=O)N1c1ccc(Cl)c(F)c1 JSLICXNQLYEHPA-YJLYGGOZSA-N 0.000 claims 1
- DBPNOZYOMBIZLU-QPPBQGQZSA-N (5S)-1-(4-chlorophenyl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]pyrrolidin-2-one Chemical compound ClC1=CC=C(C=C1)N1C(CC[C@H]1C1=NC2=C(N1[C@H]1CN(CC1)S(=O)(=O)C)C=CC(=C2)C=1C(=NOC=1C)C)=O DBPNOZYOMBIZLU-QPPBQGQZSA-N 0.000 claims 1
- OCMWWEDOZWYQGM-JPYJTQIMSA-N (5S)-1-(5-chloro-6-methoxypyridin-3-yl)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]pyrrolidin-2-one Chemical compound ClC=1C=C(C=NC=1OC)N1C(CC[C@H]1C1=NC2=C(N1[C@H]1CN(CC1)S(=O)(=O)C)C=CC(=C2)C=1C(=NOC=1C)C)=O OCMWWEDOZWYQGM-JPYJTQIMSA-N 0.000 claims 1
- FXQOZZQJZSWVCH-DEOSSOPVSA-N (5S)-5-[1-(4,4-difluorocyclohexyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(3,4-difluorophenyl)pyrrolidin-2-one Chemical compound FC1(CCC(CC1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCC(N1C1=CC(=C(C=C1)F)F)=O)F FXQOZZQJZSWVCH-DEOSSOPVSA-N 0.000 claims 1
- HRJALGCCGVUACN-DEOSSOPVSA-N (5S)-5-[1-(4,4-difluorocyclohexyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(3-fluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound COc1ccc(cc1F)N1[C@@H](CCC1=O)c1nc2cc(ccc2n1C1CCC(F)(F)CC1)-c1c(C)noc1C HRJALGCCGVUACN-DEOSSOPVSA-N 0.000 claims 1
- OQXAIQCXLLFDQG-JPYJTQIMSA-N (5S)-5-[1-[(1R)-3,3-difluorocyclopentyl]-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(3,4-difluorophenyl)pyrrolidin-2-one Chemical compound FC1(C[C@@H](CC1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCC(N1C1=CC(=C(C=C1)F)F)=O)F OQXAIQCXLLFDQG-JPYJTQIMSA-N 0.000 claims 1
- NHAIOYZVZMAVEK-IBVKSMDESA-N (5S)-5-[1-[(3R)-1-cyclopropylsulfonylpyrrolidin-3-yl]-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(3,4-difluorophenyl)pyrrolidin-2-one Chemical compound C1(CC1)S(=O)(=O)N1C[C@@H](CC1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCC(N1C1=CC(=C(C=C1)F)F)=O NHAIOYZVZMAVEK-IBVKSMDESA-N 0.000 claims 1
- SMXKSNWAZBWQMF-VWLOTQADSA-N (5S)-5-[1-[(4,4-difluorocyclohexyl)methyl]-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(3,4-difluorophenyl)pyrrolidin-2-one Chemical compound FC1(CCC(CC1)CN1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCC(N1C1=CC(=C(C=C1)F)F)=O)F SMXKSNWAZBWQMF-VWLOTQADSA-N 0.000 claims 1
- UOAIQKBWLVTYRU-SANMLTNESA-N (5S)-5-[1-benzyl-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(3,4-difluorophenyl)pyrrolidin-2-one Chemical compound C(C1=CC=CC=C1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCC(N1C1=CC(=C(C=C1)F)F)=O UOAIQKBWLVTYRU-SANMLTNESA-N 0.000 claims 1
- JWMDDGBGQPDRRZ-VWLOTQADSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(1-methylsulfonylpiperidin-4-yl)benzimidazol-2-yl]-1-(3-fluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)[C@@H]2CCC(N2C2=CC(=C(C=C2)OC)F)=O)C2CCN(CC2)S(=O)(=O)C)C=C1)C JWMDDGBGQPDRRZ-VWLOTQADSA-N 0.000 claims 1
- FGLKKHAROSYDQM-DEOSSOPVSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(2-oxaspiro[3.3]heptan-6-yl)benzimidazol-2-yl]-1-(3-fluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)[C@@H]2CCC(N2C2=CC(=C(C=C2)OC)F)=O)C2CC3(COC3)C2)C=C1)C FGLKKHAROSYDQM-DEOSSOPVSA-N 0.000 claims 1
- TVVBEZOVLLEEQW-BWKNWUBXSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(2-methylphenyl)pyrrolidin-2-one Chemical compound Cc1noc(C)c1-c1ccc2n([C@@H]3CCN(C3)S(C)(=O)=O)c(nc2c1)[C@@H]1CCC(=O)N1c1ccccc1C TVVBEZOVLLEEQW-BWKNWUBXSA-N 0.000 claims 1
- XUXNRIMMAGAVHN-HXOBKFHXSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(3,4,5-trifluorophenyl)pyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)[C@@H]2CCC(N2C2=CC(=C(C(=C2)F)F)F)=O)[C@H]2CN(CC2)S(=O)(=O)C)C=C1)C XUXNRIMMAGAVHN-HXOBKFHXSA-N 0.000 claims 1
- DGGIXPDVUABBAR-RLWLMLJZSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(3-ethoxy-5-fluorophenyl)pyrrolidin-2-one Chemical compound CCOc1cc(F)cc(c1)N1[C@@H](CCC1=O)c1nc2cc(ccc2n1[C@@H]1CCN(C1)S(C)(=O)=O)-c1c(C)noc1C DGGIXPDVUABBAR-RLWLMLJZSA-N 0.000 claims 1
- UROFXLADVMRGDG-YKSBVNFPSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(3-fluoro-4-methoxyphenyl)pyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)[C@@H]2CCC(N2C2=CC(=C(C=C2)OC)F)=O)[C@H]2CN(CC2)S(=O)(=O)C)C=C1)C UROFXLADVMRGDG-YKSBVNFPSA-N 0.000 claims 1
- RQNYVPBBMIRSAP-NLFFAJNJSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(3-fluoro-5-methoxyphenyl)pyrrolidin-2-one Chemical compound COc1cc(F)cc(c1)N1[C@@H](CCC1=O)c1nc2cc(ccc2n1[C@@H]1CCN(C1)S(C)(=O)=O)-c1c(C)noc1C RQNYVPBBMIRSAP-NLFFAJNJSA-N 0.000 claims 1
- ZBIORFWTWOHVLU-QPPBQGQZSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(3-fluorophenyl)pyrrolidin-2-one Chemical compound Cc1noc(C)c1-c1ccc2n([C@@H]3CCN(C3)S(C)(=O)=O)c(nc2c1)[C@@H]1CCC(=O)N1c1cccc(F)c1 ZBIORFWTWOHVLU-QPPBQGQZSA-N 0.000 claims 1
- MITROZSZLRKDRT-BWKNWUBXSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(4-methoxyphenyl)pyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)[C@@H]2CCC(N2C2=CC=C(C=C2)OC)=O)[C@H]2CN(CC2)S(=O)(=O)C)C=C1)C MITROZSZLRKDRT-BWKNWUBXSA-N 0.000 claims 1
- RJFAOEDALLSLDL-KCWPFWIISA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(4-propoxyphenyl)pyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)[C@@H]2CCC(N2C2=CC=C(C=C2)OCCC)=O)[C@H]2CN(CC2)S(=O)(=O)C)C=C1)C RJFAOEDALLSLDL-KCWPFWIISA-N 0.000 claims 1
- BEVXMMSVWRKZIR-QPPBQGQZSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(5-fluoro-2-methylphenyl)pyrrolidin-2-one Chemical compound Cc1noc(C)c1-c1ccc2n([C@@H]3CCN(C3)S(C)(=O)=O)c(nc2c1)[C@@H]1CCC(=O)N1c1cc(F)ccc1C BEVXMMSVWRKZIR-QPPBQGQZSA-N 0.000 claims 1
- RVVRLBMFYANMGW-XXBNENTESA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(5-fluoropyridin-3-yl)pyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)[C@@H]2CCC(N2C=2C=NC=C(C=2)F)=O)[C@H]2CN(CC2)S(=O)(=O)C)C=C1)C RVVRLBMFYANMGW-XXBNENTESA-N 0.000 claims 1
- UBSUREVLFBGHLE-KNQAVFIVSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-(6-fluoropyridin-3-yl)pyrrolidin-2-one Chemical compound Cc1noc(C)c1-c1ccc2n([C@@H]3CCN(C3)S(C)(=O)=O)c(nc2c1)[C@@H]1CCC(=O)N1c1ccc(F)nc1 UBSUREVLFBGHLE-KNQAVFIVSA-N 0.000 claims 1
- QMDOCJCAZXGSJF-YKSBVNFPSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-[3-(trifluoromethoxy)phenyl]pyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)[C@@H]2CCC(N2C2=CC(=CC=C2)OC(F)(F)F)=O)[C@H]2CN(CC2)S(=O)(=O)C)C=C1)C QMDOCJCAZXGSJF-YKSBVNFPSA-N 0.000 claims 1
- BOOCZFXGYNJSSV-LXFBAYGMSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-naphthalen-1-ylpyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)[C@@H]2CCC(N2C2=CC=CC3=CC=CC=C23)=O)[C@H]2CN(CC2)S(=O)(=O)C)C=C1)C BOOCZFXGYNJSSV-LXFBAYGMSA-N 0.000 claims 1
- BXMMBJZCICOLJZ-QPPBQGQZSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-phenylpyrrolidin-2-one Chemical compound Cc1noc(C)c1-c1ccc2n([C@@H]3CCN(C3)S(C)(=O)=O)c(nc2c1)[C@@H]1CCC(=O)N1c1ccccc1 BXMMBJZCICOLJZ-QPPBQGQZSA-N 0.000 claims 1
- RAVAVLYPMREPQF-OFNKIYASSA-N (5S)-5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-pyridin-3-ylpyrrolidin-2-one Chemical compound Cc1noc(C)c1-c1ccc2n([C@@H]3CCN(C3)S(C)(=O)=O)c(nc2c1)[C@@H]1CCC(=O)N1c1cccnc1 RAVAVLYPMREPQF-OFNKIYASSA-N 0.000 claims 1
- QLDZBTYHLKQXFE-DEOSSOPVSA-N (6S)-1-(3,4-dichlorophenyl)-6-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(2-methylpropyl)benzimidazol-2-yl]piperidin-2-one Chemical compound ClC=1C=C(C=CC=1Cl)N1C(CCC[C@H]1C1=NC2=C(N1CC(C)C)C=CC(=C2)C=1C(=NOC=1C)C)=O QLDZBTYHLKQXFE-DEOSSOPVSA-N 0.000 claims 1
- AAFAJEDKEXPZNQ-QHCPKHFHSA-N (6S)-1-(3-chloro-4-methoxyphenyl)-6-[1-(3,3-difluorocyclobutyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]piperidin-2-one Chemical compound COc1ccc(cc1Cl)N1[C@@H](CCCC1=O)c1nc2cc(ccc2n1C1CC(F)(F)C1)-c1c(C)noc1C AAFAJEDKEXPZNQ-QHCPKHFHSA-N 0.000 claims 1
- CLLWDLOQCCQDIE-VWLOTQADSA-N (6S)-1-(3-chloro-4-methoxyphenyl)-6-[1-(4,4-difluorocyclohexyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]piperidin-2-one Chemical compound ClC=1C=C(C=CC=1OC)N1C(CCC[C@H]1C1=NC2=C(N1C1CCC(CC1)(F)F)C=CC(=C2)C=1C(=NOC=1C)C)=O CLLWDLOQCCQDIE-VWLOTQADSA-N 0.000 claims 1
- WMRFYICILGNXCX-BWKNWUBXSA-N (6S)-1-(3-chloro-4-methoxyphenyl)-6-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]piperidin-2-one Chemical compound ClC=1C=C(C=CC=1OC)N1C(CCC[C@H]1C1=NC2=C(N1[C@H]1CN(CC1)S(=O)(=O)C)C=CC(=C2)C=1C(=NOC=1C)C)=O WMRFYICILGNXCX-BWKNWUBXSA-N 0.000 claims 1
- FVEITRKBGBLKCF-NLFFAJNJSA-N (6S)-1-(4-chloro-3-fluorophenyl)-6-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]piperidin-2-one Chemical compound ClC1=C(C=C(C=C1)N1C(CCC[C@H]1C1=NC2=C(N1[C@H]1CN(CC1)S(=O)(=O)C)C=CC(=C2)C=1C(=NOC=1C)C)=O)F FVEITRKBGBLKCF-NLFFAJNJSA-N 0.000 claims 1
- VNDWHNCJSUJXIC-QHCPKHFHSA-N (6S)-6-[1-(3,3-difluorocyclobutyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(3,4-difluorophenyl)piperidin-2-one Chemical compound FC1(CC(C1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCCC(N1C1=CC(=C(C=C1)F)F)=O)F VNDWHNCJSUJXIC-QHCPKHFHSA-N 0.000 claims 1
- HDBFIWQQKHMXAT-QHCPKHFHSA-N (6S)-6-[1-(3,3-difluorocyclobutyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(3-fluoro-4-methoxyphenyl)piperidin-2-one Chemical compound FC1(CC(C1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCCC(N1C1=CC(=C(C=C1)OC)F)=O)F HDBFIWQQKHMXAT-QHCPKHFHSA-N 0.000 claims 1
- PQUGYUVUHXZOPI-VWLOTQADSA-N (6S)-6-[1-(4,4-difluorocyclohexyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(3-fluoro-4-methoxyphenyl)piperidin-2-one Chemical compound FC1(CCC(CC1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCCC(N1C1=CC(=C(C=C1)OC)F)=O)F PQUGYUVUHXZOPI-VWLOTQADSA-N 0.000 claims 1
- IXJAQHDYDAVCIF-DEOSSOPVSA-N (6S)-6-[1-(4,4-difluorocyclohexyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(5-fluoropyridin-3-yl)piperidin-2-one Chemical compound FC1(CCC(CC1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCCC(N1C=1C=NC=C(C=1)F)=O)F IXJAQHDYDAVCIF-DEOSSOPVSA-N 0.000 claims 1
- CQPPQKQIMZARNE-QHCPKHFHSA-N (6S)-6-[1-(4,4-difluorocyclohexyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-(6-fluoropyridin-3-yl)piperidin-2-one Chemical compound FC1(CCC(CC1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCCC(N1C=1C=NC(=CC=1)F)=O)F CQPPQKQIMZARNE-QHCPKHFHSA-N 0.000 claims 1
- BAMWPCRLPVHXKS-VWLOTQADSA-N (6S)-6-[1-(4,4-difluorocyclohexyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-phenylpiperidin-2-one Chemical compound FC1(CCC(CC1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCCC(N1C1=CC=CC=C1)=O)F BAMWPCRLPVHXKS-VWLOTQADSA-N 0.000 claims 1
- TWKNHDVJVHDWGA-DEOSSOPVSA-N (6S)-6-[1-(4,4-difluorocyclohexyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-pyridin-3-ylpiperidin-2-one Chemical compound FC1(CCC(CC1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCCC(N1C=1C=NC=CC=1)=O)F TWKNHDVJVHDWGA-DEOSSOPVSA-N 0.000 claims 1
- WUEMDERDMAIUGD-QHCPKHFHSA-N (6S)-6-[1-(4,4-difluorocyclohexyl)-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-2-yl]-1-pyrimidin-5-ylpiperidin-2-one Chemical compound FC1(CCC(CC1)N1C(=NC2=C1C=CC(=C2)C=1C(=NOC=1C)C)[C@@H]1CCCC(N1C=1C=NC=NC=1)=O)F WUEMDERDMAIUGD-QHCPKHFHSA-N 0.000 claims 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
- NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 claims 1
- FICAQKBMCKEFDI-UHFFFAOYSA-N 3,5-dimethyl-1,2-oxazole Chemical compound CC=1C=C(C)ON=1 FICAQKBMCKEFDI-UHFFFAOYSA-N 0.000 claims 1
- LQCFDVPLJSNJSR-WGJJQBRPSA-N 3-[2-[(2S)-1-(3,4-difluorophenyl)-5-oxopyrrolidin-2-yl]-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-1-yl]-N-propylcyclobutane-1-carboxamide Chemical compound CCCNC(=O)C1CC(C1)n1c(nc2cc(ccc12)-c1c(C)noc1C)[C@@H]1CCC(=O)N1c1ccc(F)c(F)c1 LQCFDVPLJSNJSR-WGJJQBRPSA-N 0.000 claims 1
- JLAKCHGEEBPDQI-UHFFFAOYSA-N 4-(4-fluorobenzyl)piperidine Chemical compound C1=CC(F)=CC=C1CC1CCNCC1 JLAKCHGEEBPDQI-UHFFFAOYSA-N 0.000 claims 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims 1
- KSVFGSKFUBWSHR-IMMUGOHXSA-N 5-[2-[(2S)-1-(3,4-difluorophenyl)-5-oxopyrrolidin-2-yl]-5-(3,5-dimethyl-1,2-oxazol-4-yl)benzimidazol-1-yl]piperidin-2-one Chemical compound FC=1C=C(C=CC=1F)N1[C@@H](CCC1=O)C1=NC2=C(N1C1CCC(NC1)=O)C=CC(=C2)C=1C(=NOC=1C)C KSVFGSKFUBWSHR-IMMUGOHXSA-N 0.000 claims 1
- OUWIVNPJGVEQFL-UHFFFAOYSA-N 5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-(oxan-4-yl)benzimidazol-2-yl]-1-phenylpyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)C2CCC(N2C2=CC=CC=C2)=O)C2CCOCC2)C=C1)C OUWIVNPJGVEQFL-UHFFFAOYSA-N 0.000 claims 1
- BXMMBJZCICOLJZ-CILPGNKCSA-N 5-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(3R)-1-methylsulfonylpyrrolidin-3-yl]benzimidazol-2-yl]-1-phenylpyrrolidin-2-one Chemical compound CC1=NOC(=C1C1=CC2=C(N(C(=N2)C2CCC(N2C2=CC=CC=C2)=O)[C@H]2CN(CC2)S(=O)(=O)C)C=C1)C BXMMBJZCICOLJZ-CILPGNKCSA-N 0.000 claims 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims 1
- 229940123407 Androgen receptor antagonist Drugs 0.000 claims 1
- 102000013701 Cyclin-Dependent Kinase 4 Human genes 0.000 claims 1
- 108010025464 Cyclin-Dependent Kinase 4 Proteins 0.000 claims 1
- DTFYVYLWEYXYAO-VWLOTQADSA-N FC=1C=C(C=CC=1F)N1C(CC[C@H]1C1=NC2=C(N1C1CCN(CC1)S(=O)(=O)C)C=CC(=C2)C=1C(=NOC=1C)C)=O Chemical compound FC=1C=C(C=CC=1F)N1C(CC[C@H]1C1=NC2=C(N1C1CCN(CC1)S(=O)(=O)C)C=CC(=C2)C=1C(=NOC=1C)C)=O DTFYVYLWEYXYAO-VWLOTQADSA-N 0.000 claims 1
- 101000896517 Homo sapiens Steroid 17-alpha-hydroxylase/17,20 lyase Proteins 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims 1
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims 1
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims 1
- 102000004317 Lyases Human genes 0.000 claims 1
- 108090000856 Lyases Proteins 0.000 claims 1
- 241001465754 Metazoa Species 0.000 claims 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 claims 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 claims 1
- 108091000080 Phosphotransferase Proteins 0.000 claims 1
- 108010015330 Steroid 17-alpha-Hydroxylase Proteins 0.000 claims 1
- 102000001854 Steroid 17-alpha-Hydroxylase Human genes 0.000 claims 1
- 102100021719 Steroid 17-alpha-hydroxylase/17,20 lyase Human genes 0.000 claims 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 claims 1
- 230000004913 activation Effects 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 239000003936 androgen receptor antagonist Substances 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims 1
- 125000004432 carbon atom Chemical group C* 0.000 claims 1
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 1
- IUVCECHSUQJXMM-UHFFFAOYSA-N cyclobutyl acetate Chemical compound CC(=O)OC1CCC1 IUVCECHSUQJXMM-UHFFFAOYSA-N 0.000 claims 1
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims 1
- NZNMSOFKMUBTKW-UHFFFAOYSA-M cyclohexanecarboxylate Chemical compound [O-]C(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-M 0.000 claims 1
- 229940127089 cytotoxic agent Drugs 0.000 claims 1
- 230000001419 dependent effect Effects 0.000 claims 1
- 239000003085 diluting agent Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims 1
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 claims 1
- 102000020233 phosphotransferase Human genes 0.000 claims 1
- 230000000069 prophylactic effect Effects 0.000 claims 1
- 229940090181 propyl acetate Drugs 0.000 claims 1
- 238000001959 radiotherapy Methods 0.000 claims 1
- 125000003003 spiro group Chemical group 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB1617630.7 | 2016-10-18 | ||
| GBGB1617630.7A GB201617630D0 (en) | 2016-10-18 | 2016-10-18 | Pharmaceutical compounds |
| PCT/GB2017/053152 WO2018073586A1 (en) | 2016-10-18 | 2017-10-18 | Pharmaceutical compounds |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2019537571A JP2019537571A (ja) | 2019-12-26 |
| JP2019537571A5 true JP2019537571A5 (OSRAM) | 2020-11-26 |
| JP7152393B2 JP7152393B2 (ja) | 2022-10-12 |
Family
ID=57680668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2019520588A Active JP7152393B2 (ja) | 2016-10-18 | 2017-10-18 | 医薬化合物 |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US10696666B2 (OSRAM) |
| EP (1) | EP3529248B1 (OSRAM) |
| JP (1) | JP7152393B2 (OSRAM) |
| KR (1) | KR102578786B1 (OSRAM) |
| CN (1) | CN110049983B (OSRAM) |
| AU (1) | AU2017346453B2 (OSRAM) |
| CA (1) | CA3039641A1 (OSRAM) |
| CY (1) | CY1123666T1 (OSRAM) |
| DK (1) | DK3529248T3 (OSRAM) |
| EA (1) | EA201990643A1 (OSRAM) |
| ES (1) | ES2828504T3 (OSRAM) |
| GB (1) | GB201617630D0 (OSRAM) |
| HR (1) | HRP20201444T1 (OSRAM) |
| HU (1) | HUE052443T2 (OSRAM) |
| IL (1) | IL266017B (OSRAM) |
| LT (1) | LT3529248T (OSRAM) |
| MX (1) | MX384438B (OSRAM) |
| PT (1) | PT3529248T (OSRAM) |
| RS (1) | RS61007B1 (OSRAM) |
| SG (1) | SG11201903155XA (OSRAM) |
| SI (1) | SI3529248T1 (OSRAM) |
| SM (1) | SMT202000593T1 (OSRAM) |
| WO (1) | WO2018073586A1 (OSRAM) |
| ZA (1) | ZA201902334B (OSRAM) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201617630D0 (en) | 2016-10-18 | 2016-11-30 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201617627D0 (en) * | 2016-10-18 | 2016-11-30 | Cellcentric Ltd | Pharmaceutical compounds |
| WO2019055877A1 (en) | 2017-09-15 | 2019-03-21 | Forma Therapeutics, Inc. | TETRAHYDROIMIDAZO QUINOLINE COMPOSITIONS AS INHIBITORS OF CBP / P300 |
| GB201806320D0 (en) * | 2018-04-18 | 2018-05-30 | Cellcentric Ltd | Process |
| AU2019295790B2 (en) | 2018-06-29 | 2023-07-13 | Forma Therapeutics, Inc. | Inhibiting creb binding protein (CBP) |
| WO2020190791A1 (en) | 2019-03-15 | 2020-09-24 | Forma Therapeutics, Inc. | Inhibiting cyclic amp-responsive element-binding protein (creb) |
| CN119684285A (zh) * | 2019-03-15 | 2025-03-25 | 福马治疗股份有限公司 | 抑制环amp-应答元件结合蛋白(creb) |
| CN112574189B (zh) * | 2019-09-27 | 2024-05-31 | 海创药业股份有限公司 | 一种ep300/cbp抑制剂 |
| CN112574191B (zh) * | 2019-09-29 | 2024-01-23 | 南京圣和药业股份有限公司 | 异噁唑杂环类化合物及其应用 |
| JP2023532675A (ja) | 2020-06-25 | 2023-07-31 | トルレモ・セラピューティクス・アクチェンゲゼルシャフト | ＥＧＦＲ突然変異ＮＳＣＬＣの治療に使用するための、ＣＢＰ／ｐ３００ブロモドメイン阻害剤およびＥＧＦＲ阻害剤の組合せ |
| US12472179B2 (en) | 2020-06-25 | 2025-11-18 | Tolremo Therapeutics Ag | Combination of a CBP/p300 bromodomain inhibitor and a KRAS inhibitor for the treatment of cancer |
| 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) |
| TW202227429A (zh) * | 2020-11-06 | 2022-07-16 | 大陸商貝達藥業股份有限公司 | Ｐ３００抑制劑、包含其的藥物組合物、其應用及製備其的方法 |
| US20240122941A1 (en) * | 2020-12-25 | 2024-04-18 | National Cancer Center | Therapy based on synthetic lethality in swi/snf complex-dysfunction cancer |
| WO2022143773A1 (zh) * | 2020-12-31 | 2022-07-07 | 南京明德新药研发有限公司 | 苯并咪唑类化合物及其应用 |
| CN114989158A (zh) * | 2021-03-02 | 2022-09-02 | 复旦大学 | 组蛋白乙酰转移酶p300溴结构域抑制剂及其药用组合物及其应用 |
| WO2022184664A1 (en) | 2021-03-02 | 2022-09-09 | Boehringer Ingelheim International Gmbh | Anticancer combination therapy |
| EP4257130A1 (de) * | 2022-04-08 | 2023-10-11 | Justus-Liebig-Universität Gießen | Inobrodib zur behandlung von pulmonaler arterieller hypertonie |
Family Cites Families (55)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PE27997A1 (es) | 1994-04-29 | 1997-09-20 | Lilly Co Eli | Antagonistas de receptores de taquicininas |
| EP1206265B1 (en) * | 1999-06-30 | 2003-11-12 | Merck & Co., Inc. | Src kinase inhibitor compounds |
| WO2002028839A1 (en) | 2000-10-06 | 2002-04-11 | Neurogen Corporation | Benzimidazole and indole derivatives as crf receptor modulators |
| EP1377549A1 (en) | 2001-03-12 | 2004-01-07 | Millennium Pharmaceuticals, Inc. | Functionalized heterocycles as modulators of chemokine receptor function and methods of use therefor |
| ES2292937T3 (es) | 2002-02-21 | 2008-03-16 | Eli Lilly And Company | Moduladores para el receptor activado por el proliferador de peroxisomas. |
| US7189716B2 (en) | 2003-01-03 | 2007-03-13 | Bristol-Myers Squibb Company | Tyrosine kinase inhibitors |
| US7312215B2 (en) | 2003-07-29 | 2007-12-25 | Bristol-Myers Squibb Company | Benzimidazole C-2 heterocycles as kinase inhibitors |
| WO2005118555A1 (en) | 2004-06-04 | 2005-12-15 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| WO2006124780A2 (en) | 2005-05-12 | 2006-11-23 | Kalypsys, Inc. | Ih-benzo [d] imidazole compounds as inhibitors of b-raf kinase |
| WO2006136823A1 (en) | 2005-06-21 | 2006-12-28 | Astex Therapeutics Limited | Heterocyclic containing amines as kinase b inhibitors |
| ES2570994T3 (es) * | 2005-11-08 | 2016-05-23 | Choongwae Pharma Corp | Miméticos de alfa-hélice y método relacionados con el tratamiento de células madre de cáncer |
| EP1878724A1 (en) | 2006-07-15 | 2008-01-16 | sanofi-aventis | A regioselective palladium catalyzed synthesis of benzimidazoles and azabenzimidazoles |
| CN101616587A (zh) | 2006-12-05 | 2009-12-30 | 孙仲铭 | 吲唑化合物 |
| JP5492770B2 (ja) | 2007-06-26 | 2014-05-14 | サノフイ | ベンゾイミダゾール及びアザベンゾイミダゾールの位置選択的銅触媒合成 |
| EA201000201A1 (ru) | 2007-08-10 | 2010-12-30 | ГЛАКСОСМИТКЛАЙН ЭлЭлСи | Азотсодержащие бициклические химические вещества для лечения вирусных инфекций |
| EP2234487A4 (en) | 2007-12-19 | 2011-09-07 | Scripps Research Inst | ANILIDES AND ANALOGUES AS INHIBITORS OF RHO KINASE |
| US8501957B2 (en) | 2008-12-10 | 2013-08-06 | China Medical University | Benzimidazole compounds and their use as anticancer agents |
| WO2010068287A2 (en) | 2008-12-11 | 2010-06-17 | Angion Biomedica Corp. | Small molecule modulators of hepatocyte growth factor (scatter factor) activity |
| WO2010075282A1 (en) | 2008-12-22 | 2010-07-01 | University Of Washington | Molecular inhibitors of the wnt/beta-catenin pathway |
| ES2620177T3 (es) | 2009-10-15 | 2017-06-27 | Guerbet | Agentes de formación de imágenes y su uso para el diagnóstico in vivo de enfermedades neurodegenerativas, particularmente la enfermedad de Alzheimer y enfermedades derivadas |
| WO2011085039A2 (en) * | 2010-01-05 | 2011-07-14 | The Johns Hopkins University | Use of histone acetyltransferase inhibitors as novel anti-cancer therapies |
| US8455516B2 (en) | 2010-01-15 | 2013-06-04 | Touro University | HIV-1 fusion inhibitors and methods |
| WO2011097607A1 (en) | 2010-02-08 | 2011-08-11 | Southern Research Institute | Anti-viral treatment and assay to screen for anti-viral agent |
| MX2012013128A (es) | 2010-05-13 | 2013-03-20 | Amgen Inc | Compuestos heterociclicos de nitrogeno como inhibidores de la fosfodiesterasa 10. |
| EP2397471A1 (en) | 2010-06-16 | 2011-12-21 | China Medical University | Benzimidazole compounds and their use |
| WO2012036168A1 (ja) | 2010-09-14 | 2012-03-22 | 北海道公立大学法人札幌医科大学 | 筋ジストロフィーを処置するための組成物 |
| US8653089B2 (en) | 2011-02-09 | 2014-02-18 | F. Hoffmann-La Roche Ag | Heterocyclic compounds and methods of use |
| EP2681200A4 (en) | 2011-03-03 | 2015-05-27 | Zalicus Pharmaceuticals Ltd | INHIBITORS OF BENZIMIDAZOLE TYPE OF SODIUM CHANNEL |
| JP2014114212A (ja) | 2011-03-29 | 2014-06-26 | Dainippon Sumitomo Pharma Co Ltd | 新規ベンズイミダゾール誘導体 |
| TW201348231A (zh) | 2012-02-29 | 2013-12-01 | Amgen Inc | 雜雙環化合物 |
| CN104428293B (zh) | 2012-06-11 | 2018-06-08 | Ucb生物制药私人有限公司 | 调节TNFα的苯并咪唑类 |
| WO2014012050A2 (en) | 2012-07-13 | 2014-01-16 | Indiana University Research & Technology Corporation | Compounds for treatment of spinal muscular atrophy |
| JP2016000697A (ja) | 2012-10-02 | 2016-01-07 | 大日本住友製薬株式会社 | ピリミジン誘導体 |
| JP2014073982A (ja) | 2012-10-03 | 2014-04-24 | Dainippon Sumitomo Pharma Co Ltd | 新規ベンズイミダゾール誘導体からなる医薬 |
| WO2014078479A2 (en) | 2012-11-14 | 2014-05-22 | The Board Of Regents Of The University Of Texas System | INHIBITION OF HIF-2α HETERODIMERIZATION WITH HIF1β (ARNT) |
| WO2014157382A1 (ja) | 2013-03-29 | 2014-10-02 | 味の素株式会社 | スフィンゴシンキナーゼ阻害剤 |
| PL231063B1 (pl) | 2013-04-10 | 2019-01-31 | Oncoarendi Therapeutics Spolka Z Ograniczona Odpowiedzialnoscia | Pochodne 1-(podstawionej sulfonylo)-2-aminoimidazoliny jako środki przeciwnowotworowe |
| TWI527811B (zh) * | 2013-05-09 | 2016-04-01 | 吉李德科學股份有限公司 | 作爲溴結構域抑制劑的苯並咪唑衍生物 |
| ES2661437T3 (es) | 2013-06-21 | 2018-04-02 | Zenith Epigenetics Corp. | Nuevos compuestos bicíclicos sustituidos como inhibidores de bromodominio |
| WO2015023958A1 (en) | 2013-08-15 | 2015-02-19 | The University Of Kansas | Toll-like receptor agonists |
| GB201321741D0 (en) | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| BR112017001918A2 (pt) | 2014-07-31 | 2017-11-28 | Pasteur Institut Korea | derivados de 2-amino-benzimidazol e seu uso como inibidores de 5-lipoxigenase e/ou prostaglandina e sintase |
| WO2016086200A1 (en) * | 2014-11-27 | 2016-06-02 | Genentech, Inc. | 4,5,6,7-tetrahydro-1 h-pyrazolo[4,3-c]pyridin-3-amine compounds as cbp and/or ep300 inhibitors |
| GB201506660D0 (en) * | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201506658D0 (en) * | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| US10875833B2 (en) | 2015-06-12 | 2020-12-29 | Transitions Optical, Inc. | Alignment compounds |
| WO2017024412A1 (en) | 2015-08-12 | 2017-02-16 | Neomed Institute | Substituted benzimidazoles, their preparation and their use as pharmaceuticals |
| JP2018534263A (ja) | 2015-10-02 | 2018-11-22 | ギリアード サイエンシーズ， インコーポレイテッド | 癌、アレルギー性障害、自己免疫性疾患または炎症性疾患を治療するための、ｊａｋ阻害物質、ａｓｋ１阻害物質、ｂｒｄ阻害物質及び／またはｍｍｐ９阻害物質から選択される阻害物質とｂｔｋ阻害物質ｇｓ−４０５９の組み合わせ |
| CA3007988A1 (en) | 2015-12-11 | 2017-06-15 | The Board Of Regents Of The University Of Texas System | Substituted benzimidazolium, pyrido-imidazolium, or pyrazino-imidazolium compounds as chemotherapeutics |
| WO2017106568A1 (en) | 2015-12-17 | 2017-06-22 | Gilead Sciences, Inc. | Combination of a jak inhibitor and a bromodomain inhibitor for treating cancer |
| CN109640988A (zh) | 2016-06-21 | 2019-04-16 | X4 制药有限公司 | Cxcr4抑制剂及其用途 |
| WO2017223243A1 (en) | 2016-06-21 | 2017-12-28 | X4 Pharmaceuticals, Inc. | Cxcr4 inhibitors and uses thereof |
| GB201617630D0 (en) | 2016-10-18 | 2016-11-30 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201617627D0 (en) * | 2016-10-18 | 2016-11-30 | Cellcentric Ltd | Pharmaceutical compounds |
| US20180179191A1 (en) | 2016-11-22 | 2018-06-28 | Gilead Sciences, Inc. | Synthesis of a compound that modulates the activity of bromodomain-containing proteins |
-
2016
- 2016-10-18 GB GBGB1617630.7A patent/GB201617630D0/en not_active Ceased
-
2017
- 2017-10-18 JP JP2019520588A patent/JP7152393B2/ja active Active
- 2017-10-18 SG SG11201903155XA patent/SG11201903155XA/en unknown
- 2017-10-18 US US16/341,631 patent/US10696666B2/en active Active
- 2017-10-18 HR HRP20201444TT patent/HRP20201444T1/hr unknown
- 2017-10-18 CN CN201780072401.XA patent/CN110049983B/zh active Active
- 2017-10-18 ES ES17790813T patent/ES2828504T3/es active Active
- 2017-10-18 LT LTEP17790813.4T patent/LT3529248T/lt unknown
- 2017-10-18 EP EP17790813.4A patent/EP3529248B1/en active Active
- 2017-10-18 CA CA3039641A patent/CA3039641A1/en active Pending
- 2017-10-18 AU AU2017346453A patent/AU2017346453B2/en active Active
- 2017-10-18 SI SI201730402T patent/SI3529248T1/sl unknown
- 2017-10-18 SM SM20200593T patent/SMT202000593T1/it unknown
- 2017-10-18 RS RS20201314A patent/RS61007B1/sr unknown
- 2017-10-18 WO PCT/GB2017/053152 patent/WO2018073586A1/en not_active Ceased
- 2017-10-18 DK DK17790813.4T patent/DK3529248T3/da active
- 2017-10-18 PT PT177908134T patent/PT3529248T/pt unknown
- 2017-10-18 EA EA201990643A patent/EA201990643A1/ru unknown
- 2017-10-18 HU HUE17790813A patent/HUE052443T2/hu unknown
- 2017-10-18 MX MX2019004113A patent/MX384438B/es unknown
- 2017-10-18 KR KR1020197014352A patent/KR102578786B1/ko active Active
-
2019
- 2019-04-12 ZA ZA2019/02334A patent/ZA201902334B/en unknown
- 2019-04-14 IL IL266017A patent/IL266017B/en unknown
-
2020
- 2020-05-14 US US15/931,782 patent/US11377443B2/en active Active
- 2020-11-19 CY CY20201101096T patent/CY1123666T1/el unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2019537571A5 (OSRAM) | ||
| HRP20201444T1 (hr) | Farmaceutski spojevi | |
| JP2016519156A5 (OSRAM) | ||
| RU2485114C2 (ru) | Карбоксамидные соединения и их применение в качестве ингибиторов кальпаинов | |
| JP2018530591A5 (OSRAM) | ||
| IL295799A (en) | Trophomyosin receptor kinase (trk) degradation compounds and methods of use | |
| JP2021500345A5 (OSRAM) | ||
| RU2014139601A (ru) | Ингибиторы серин/треониновых киназ | |
| JP2019535658A5 (OSRAM) | ||
| JP2017500364A5 (OSRAM) | ||
| JP2019530695A5 (OSRAM) | ||
| JP2010533158A5 (OSRAM) | ||
| JP2019518036A5 (OSRAM) | ||
| IL258577A (en) | 2,4-dihydroxy-nicotinamides as apj agonists | |
| JP2020515575A5 (OSRAM) | ||
| RU2015154987A (ru) | Гетероциклические производные | |
| JP2015508828A5 (OSRAM) | ||
| JP2011500806A5 (OSRAM) | ||
| JP2020506946A5 (OSRAM) | ||
| NZ609955A (en) | Sgc stimulators | |
| RU2011114487A (ru) | Гетероциклические соединения как ингибиторы протеинкиназы | |
| RU2008117329A (ru) | Производные имидазопиридина как антагонисты аденозинового рецептора а2в | |
| RU2019132212A (ru) | Селективные ингибиторы hdac6 | |
| RU2014150049A (ru) | Ингибиторы nampt | |
| RU2018131775A (ru) | 6-арил-4-морфолин-1-илпиридоны, пригодные для лечения рака или диабета |