JP2018510203A5 - - Google Patents
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- Publication number
- JP2018510203A5 JP2018510203A5 JP2017551712A JP2017551712A JP2018510203A5 JP 2018510203 A5 JP2018510203 A5 JP 2018510203A5 JP 2017551712 A JP2017551712 A JP 2017551712A JP 2017551712 A JP2017551712 A JP 2017551712A JP 2018510203 A5 JP2018510203 A5 JP 2018510203A5
- Authority
- JP
- Japan
- Prior art keywords
- oxo
- methyl
- methoxy
- alkyl
- benzo
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- -1 amino, hydrazino, formyl Chemical group 0.000 claims description 81
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 34
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 31
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 6
- 201000010099 disease Diseases 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 5
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 4
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 241000124008 Mammalia Species 0.000 claims description 3
- 230000002062 proliferating effect Effects 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- GWMRWQFYXYMLMC-UHFFFAOYSA-N 2-(7-cyclohexyl-9-methoxy-2-methyl-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl)-N-ethylacetamide Chemical compound CCNC(=O)CC1OC(C2CCCCC2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 GWMRWQFYXYMLMC-UHFFFAOYSA-N 0.000 claims description 2
- UVTKTBNWUZYOKN-UHFFFAOYSA-N 2-(7-cyclohexyl-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl)-N-ethylacetamide Chemical compound CCNC(=O)CC1N=C(C2CCCCC2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 UVTKTBNWUZYOKN-UHFFFAOYSA-N 0.000 claims description 2
- DZDZAADAXHEPIX-NRFANRHFSA-N 2-[(5S)-7-(cyclopropylmethyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound C1(CC1)CC1=N[C@H](C=2C(C3=C1C=C(C=C3)OC)=CN(C(C=2)=O)C)CC(=O)NCC DZDZAADAXHEPIX-NRFANRHFSA-N 0.000 claims description 2
- XKKJWRPBHOFDIX-WIOPSUGQSA-N 2-[(5S,7R)-7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]-N-ethylacetamide Chemical compound ClC1=CC=C(C=C1)[C@@H]1C2=C(C3=CN(C(C=C3[C@@H](O1)CC(=O)NCC)=O)C)C=CC(=C2)OC XKKJWRPBHOFDIX-WIOPSUGQSA-N 0.000 claims description 2
- GWMRWQFYXYMLMC-WIOPSUGQSA-N 2-[(5S,7R)-7-cyclohexyl-9-methoxy-2-methyl-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]-N-ethylacetamide Chemical compound CCNC(=O)C[C@@H]1O[C@H](C2CCCCC2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 GWMRWQFYXYMLMC-WIOPSUGQSA-N 0.000 claims description 2
- LCPMVCRFZNKMPK-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-2-methyl-3-oxo-9-(trifluoromethyl)-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]-N-ethylacetamide Chemical compound ClC1=CC=C(C=C1)C1C2=C(C3=CN(C(C=C3C(O1)CC(=O)NCC)=O)C)C=CC(=C2)C(F)(F)F LCPMVCRFZNKMPK-UHFFFAOYSA-N 0.000 claims description 2
- SNPLKNKISKSAQY-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-9-(difluoromethoxy)-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound CCNC(=O)CC1N=C(c2ccc(Cl)cc2)c2cc(OC(F)F)ccc2-c2cn(C)c(=O)cc12 SNPLKNKISKSAQY-UHFFFAOYSA-N 0.000 claims description 2
- OYNLWORWRWWIME-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-9-fluoro-2-methyl-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]-N-ethylacetamide Chemical compound CCNC(=O)CC1OC(c2ccc(Cl)cc2)c2cc(F)ccc2-c2cn(C)c(=O)cc12 OYNLWORWRWWIME-UHFFFAOYSA-N 0.000 claims description 2
- XPWOMOKPAAIWAP-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound CCNC(=O)CC1N=C(c2ccc(Cl)cc2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 XPWOMOKPAAIWAP-UHFFFAOYSA-N 0.000 claims description 2
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- GKECDORWWXXNRY-UHFFFAOYSA-N 2h-pyridin-3-one Chemical compound O=C1CN=CC=C1 GKECDORWWXXNRY-UHFFFAOYSA-N 0.000 claims description 2
- OZLNDJCCYVBJME-UHFFFAOYSA-N 7-(4-chlorophenyl)-9-methoxy-2-methyl-5H-pyrido[4,3-d][2]benzazepin-3-one Chemical compound COc1ccc2-c3cn(C)c(=O)cc3CN=C(c3ccc(Cl)cc3)c2c1 OZLNDJCCYVBJME-UHFFFAOYSA-N 0.000 claims description 2
- MXWXMMPQLASWKE-XUZZJYLKSA-N CCNC(=O)C[C@H]1C2=CC(=O)N(C=C2C3=C(C=C(C=C3)F)[C@H](O1)C4=CC=CC=C4)C Chemical compound CCNC(=O)C[C@H]1C2=CC(=O)N(C=C2C3=C(C=C(C=C3)F)[C@H](O1)C4=CC=CC=C4)C MXWXMMPQLASWKE-XUZZJYLKSA-N 0.000 claims description 2
- MXWXMMPQLASWKE-URXFXBBRSA-N N-ethyl-2-[(5S,7S)-9-fluoro-2-methyl-3-oxo-7-phenyl-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]acetamide Chemical compound CCNC(=O)C[C@@H]1O[C@@H](c2ccccc2)c2cc(F)ccc2-c2cn(C)c(=O)cc12 MXWXMMPQLASWKE-URXFXBBRSA-N 0.000 claims description 2
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 2
- 231100000433 cytotoxic Toxicity 0.000 claims description 2
- 229940127089 cytotoxic agent Drugs 0.000 claims description 2
- 239000002254 cytotoxic agent Substances 0.000 claims description 2
- 230000001472 cytotoxic effect Effects 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 231100000065 noncytotoxic Toxicity 0.000 claims description 2
- 230000002020 noncytotoxic effect Effects 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 62
- 125000001072 heteroaryl group Chemical group 0.000 claims 46
- 125000003118 aryl group Chemical group 0.000 claims 42
- 229910052739 hydrogen Inorganic materials 0.000 claims 42
- 239000001257 hydrogen Substances 0.000 claims 42
- GJVFBWCTGUSGDD-UHFFFAOYSA-L pentamethonium bromide Chemical compound [Br-].[Br-].C[N+](C)(C)CCCCC[N+](C)(C)C GJVFBWCTGUSGDD-UHFFFAOYSA-L 0.000 claims 37
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 28
- 150000002431 hydrogen Chemical class 0.000 claims 28
- 125000001188 haloalkyl group Chemical group 0.000 claims 25
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims 23
- 229910052736 halogen Inorganic materials 0.000 claims 21
- 150000002367 halogens Chemical class 0.000 claims 21
- 125000000623 heterocyclic group Chemical group 0.000 claims 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims 16
- 125000000753 cycloalkyl group Chemical group 0.000 claims 16
- 125000004438 haloalkoxy group Chemical group 0.000 claims 16
- 125000006696 (C2-C18) heterocyclyl group Chemical group 0.000 claims 15
- 125000003545 alkoxy group Chemical group 0.000 claims 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 14
- 125000001424 substituent group Chemical group 0.000 claims 14
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims 13
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 13
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 12
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 12
- 239000000460 chlorine Substances 0.000 claims 11
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 10
- KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical compound [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 claims 9
- 229910052801 chlorine Inorganic materials 0.000 claims 9
- 229910052731 fluorine Inorganic materials 0.000 claims 9
- 239000011737 fluorine Substances 0.000 claims 9
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims 9
- 125000004043 oxo group Chemical group O=* 0.000 claims 9
- 125000000464 thioxo group Chemical group S=* 0.000 claims 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 8
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 8
- 229910052794 bromium Inorganic materials 0.000 claims 8
- 125000005842 heteroatom Chemical group 0.000 claims 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims 7
- 229910052757 nitrogen Inorganic materials 0.000 claims 7
- 125000002252 acyl group Chemical group 0.000 claims 6
- 125000001153 fluoro group Chemical group F* 0.000 claims 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 6
- 229910052760 oxygen Inorganic materials 0.000 claims 6
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims 5
- 229930194542 Keto Natural products 0.000 claims 5
- 125000003342 alkenyl group Chemical group 0.000 claims 5
- 125000003282 alkyl amino group Chemical group 0.000 claims 5
- 125000000304 alkynyl group Chemical group 0.000 claims 5
- 125000001246 bromo group Chemical group Br* 0.000 claims 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims 5
- 125000002346 iodo group Chemical group I* 0.000 claims 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 5
- 125000000468 ketone group Chemical group 0.000 claims 5
- 229910052717 sulfur Inorganic materials 0.000 claims 5
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 4
- 125000004423 acyloxy group Chemical group 0.000 claims 4
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims 4
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims 4
- DYMRYCZRMAHYKE-UHFFFAOYSA-N n-diazonitramide Chemical compound [O-][N+](=O)N=[N+]=[N-] DYMRYCZRMAHYKE-UHFFFAOYSA-N 0.000 claims 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 4
- 229940124530 sulfonamide Drugs 0.000 claims 4
- 150000003456 sulfonamides Chemical class 0.000 claims 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 4
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 3
- 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 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 3
- 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 claims 3
- 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 claims 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 3
- 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 claims 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims 3
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims 3
- XKKJWRPBHOFDIX-DHLKQENFSA-N 2-[(5S,7S)-7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]-N-ethylacetamide Chemical compound ClC1=CC=C(C=C1)[C@H]1C2=C(C3=CN(C(C=C3[C@@H](O1)CC(=O)NCC)=O)C)C=CC(=C2)OC XKKJWRPBHOFDIX-DHLKQENFSA-N 0.000 claims 2
- JCAZXVOHALWELW-UHFFFAOYSA-N 4,5-dihydroazepin-3-one Chemical compound O=C1CCC=CN=C1 JCAZXVOHALWELW-UHFFFAOYSA-N 0.000 claims 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 102000001805 Bromodomains Human genes 0.000 claims 2
- 108050009021 Bromodomains Proteins 0.000 claims 2
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims 2
- 239000004305 biphenyl Substances 0.000 claims 2
- 235000010290 biphenyl Nutrition 0.000 claims 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 125000002541 furyl group Chemical group 0.000 claims 2
- 125000002883 imidazolyl group Chemical group 0.000 claims 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims 2
- 125000001041 indolyl group Chemical group 0.000 claims 2
- 125000000842 isoxazolyl group Chemical group 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- 125000002971 oxazolyl group Chemical group 0.000 claims 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000000168 pyrrolyl group Chemical group 0.000 claims 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims 2
- 125000000335 thiazolyl group Chemical group 0.000 claims 2
- 125000001544 thienyl group Chemical group 0.000 claims 2
- 125000004306 triazinyl group Chemical group 0.000 claims 2
- UVTKTBNWUZYOKN-QFIPXVFZSA-N 2-[(5S)-7-cyclohexyl-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound C1(CCCCC1)C1=N[C@H](C=2C(C3=C1C=C(C=C3)OC)=CN(C(C=2)=O)C)CC(=O)NCC UVTKTBNWUZYOKN-QFIPXVFZSA-N 0.000 claims 1
- IFJPDWTXTNMEHW-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-2-methyl-3-oxo-9-(trifluoromethyl)-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetic acid Chemical compound ClC1=CC=C(C=C1)C1=NC(C=2C(C3=C1C=C(C=C3)C(F)(F)F)=CN(C(C=2)=O)C)CC(=O)O IFJPDWTXTNMEHW-UHFFFAOYSA-N 0.000 claims 1
- DZDZAADAXHEPIX-UHFFFAOYSA-N 2-[7-(cyclopropylmethyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound CCNC(=O)CC1N=C(CC2CC2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 DZDZAADAXHEPIX-UHFFFAOYSA-N 0.000 claims 1
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims 1
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims 1
- 241000239366 Euphausiacea Species 0.000 claims 1
- PMDCZENCAXMSOU-UHFFFAOYSA-N N-Ethylacetamide Natural products CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 claims 1
- JOWNYTJTMJPZHA-INIZCTEOSA-N N-ethyl-2-[(5S)-9-methoxy-2-methyl-3-oxo-7-(trifluoromethyl)-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetamide Chemical compound COC=1C=CC2=C(C(=N[C@H](C=3C2=CN(C(C=3)=O)C)CC(=O)NCC)C(F)(F)F)C=1 JOWNYTJTMJPZHA-INIZCTEOSA-N 0.000 claims 1
- UJULDZHZBWSWFE-WIOPSUGQSA-N N-ethyl-2-[(5S,7R)-9-methoxy-2-methyl-7-(5-methylpyridin-2-yl)-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]acetamide Chemical compound CCNC(=O)C[C@@H]1O[C@@H](c2ccc(C)cn2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 UJULDZHZBWSWFE-WIOPSUGQSA-N 0.000 claims 1
- UJULDZHZBWSWFE-DHLKQENFSA-N N-ethyl-2-[(5S,7S)-9-methoxy-2-methyl-7-(5-methylpyridin-2-yl)-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]acetamide Chemical compound CCNC(=O)C[C@@H]1O[C@H](c2ccc(C)cn2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 UJULDZHZBWSWFE-DHLKQENFSA-N 0.000 claims 1
- GWMRWQFYXYMLMC-DHLKQENFSA-N [H][C@@]1(CC(=O)NCC)O[C@@]([H])(C2CCCCC2)C2=C(C=CC(OC)=C2)C2=CN(C)C(=O)C=C12 Chemical compound [H][C@@]1(CC(=O)NCC)O[C@@]([H])(C2CCCCC2)C2=C(C=CC(OC)=C2)C2=CN(C)C(=O)C=C12 GWMRWQFYXYMLMC-DHLKQENFSA-N 0.000 claims 1
- JOJCYVQTJJNZMC-SFTDATJTSA-N [H][C@@]1(CC2CC2)O[C@@]([H])(CC(=O)NCC)C2=CC(=O)N(C)C=C2C2=C1C=C(OC)C=C2 Chemical compound [H][C@@]1(CC2CC2)O[C@@]([H])(CC(=O)NCC)C2=CC(=O)N(C)C=C2C2=C1C=C(OC)C=C2 JOJCYVQTJJNZMC-SFTDATJTSA-N 0.000 claims 1
- JOJCYVQTJJNZMC-RTWAWAEBSA-N [H][C@]1(CC2CC2)O[C@@]([H])(CC(=O)NCC)C2=CC(=O)N(C)C=C2C2=C1C=C(OC)C=C2 Chemical compound [H][C@]1(CC2CC2)O[C@@]([H])(CC(=O)NCC)C2=CC(=O)N(C)C=C2C2=C1C=C(OC)C=C2 JOJCYVQTJJNZMC-RTWAWAEBSA-N 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- NZKFFGZDNRWTTP-UHFFFAOYSA-N azidocyanamide Chemical compound [N-]=[N+]=NNC#N NZKFFGZDNRWTTP-UHFFFAOYSA-N 0.000 claims 1
- 150000001804 chlorine Chemical group 0.000 claims 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
- 125000004119 disulfanediyl group Chemical group *SS* 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000000338 in vitro Methods 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 239000000543 intermediate Substances 0.000 claims 1
- 230000001404 mediated effect Effects 0.000 claims 1
- 239000002207 metabolite Substances 0.000 claims 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- 239000000651 prodrug Substances 0.000 claims 1
- 229940002612 prodrug Drugs 0.000 claims 1
- 125000006000 trichloroethyl group Chemical group 0.000 claims 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000002519 immonomodulatory effect Effects 0.000 description 2
- JCUHOPOAPQOACK-CYBMUJFWSA-N (5R)-7-(4-chlorophenyl)-9-methoxy-2,5-dimethyl-5H-pyrido[4,3-d][2]benzazepin-3-one Chemical compound ClC1=CC=C(C=C1)C1=N[C@@H](C=2C(C3=C1C=C(C=C3)OC)=CN(C(C=2)=O)C)C JCUHOPOAPQOACK-CYBMUJFWSA-N 0.000 description 1
- XPWOMOKPAAIWAP-JOCHJYFZSA-N 2-[(5R)-7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound ClC1=CC=C(C=C1)C1=N[C@@H](C=2C(C3=C1C=C(C=C3)OC)=CN(C(C=2)=O)C)CC(=O)NCC XPWOMOKPAAIWAP-JOCHJYFZSA-N 0.000 description 1
- DZDZAADAXHEPIX-OAQYLSRUSA-N 2-[(5R)-7-(cyclopropylmethyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound C1(CC1)CC1=N[C@@H](C=2C(C3=C1C=C(C=C3)OC)=CN(C(C=2)=O)C)CC(=O)NCC DZDZAADAXHEPIX-OAQYLSRUSA-N 0.000 description 1
- UVTKTBNWUZYOKN-JOCHJYFZSA-N 2-[(5R)-7-cyclohexyl-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound C1(CCCCC1)C1=N[C@@H](C=2C(C3=C1C=C(C=C3)OC)=CN(C(C=2)=O)C)CC(=O)NCC UVTKTBNWUZYOKN-JOCHJYFZSA-N 0.000 description 1
- XKKJWRPBHOFDIX-RDGATRHJSA-N 2-[(5R,7S)-7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]-N-ethylacetamide Chemical compound ClC1=CC=C(C=C1)[C@H]1C2=C(C3=CN(C(C=C3[C@H](O1)CC(=O)NCC)=O)C)C=CC(=C2)OC XKKJWRPBHOFDIX-RDGATRHJSA-N 0.000 description 1
- XPWOMOKPAAIWAP-QFIPXVFZSA-N 2-[(5S)-7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound ClC1=CC=C(C=C1)C1=N[C@H](C=2C(C3=C1C=C(C=C3)OC)=CN(C(C=2)=O)C)CC(=O)NCC XPWOMOKPAAIWAP-QFIPXVFZSA-N 0.000 description 1
- QDPGWGQWPZJTJP-UHFFFAOYSA-N 2-[7-(2,6-difluorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound CCNC(=O)CC1N=C(c2cc(OC)ccc2-c2cn(C)c(=O)cc12)c1c(F)cccc1F QDPGWGQWPZJTJP-UHFFFAOYSA-N 0.000 description 1
- SWJQCPVEONTBRW-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-2-methyl-3-oxo-9-(trifluoromethyl)-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound CCNC(=O)CC1N=C(c2ccc(Cl)cc2)c2cc(ccc2-c2cn(C)c(=O)cc12)C(F)(F)F SWJQCPVEONTBRW-UHFFFAOYSA-N 0.000 description 1
- UNSWYYOVDKQJRL-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-9-hydroxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound CCNC(=O)CC1N=C(c2ccc(Cl)cc2)c2cc(O)ccc2-c2cn(C)c(=O)cc12 UNSWYYOVDKQJRL-UHFFFAOYSA-N 0.000 description 1
- XIYHIOVDPTWXGT-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-9-methoxy-3-oxo-2-propan-2-yl-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound CCNC(=O)CC1N=C(c2ccc(Cl)cc2)c2cc(OC)ccc2-c2cn(C(C)C)c(=O)cc12 XIYHIOVDPTWXGT-UHFFFAOYSA-N 0.000 description 1
- QJJREWSXFZJDJA-UHFFFAOYSA-N 2-[7-(4-cyanophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide Chemical compound CCNC(=O)CC1N=C(c2ccc(cc2)C#N)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 QJJREWSXFZJDJA-UHFFFAOYSA-N 0.000 description 1
- JOJCYVQTJJNZMC-UHFFFAOYSA-N 2-[7-(cyclopropylmethyl)-9-methoxy-2-methyl-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]-N-ethylacetamide Chemical compound CCNC(=O)CC1OC(CC2CC2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 JOJCYVQTJJNZMC-UHFFFAOYSA-N 0.000 description 1
- TVFBIJNOBAXMEN-UHFFFAOYSA-N N-[[7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]methyl]acetamide Chemical compound C(C)(=O)NCC1C=2C(C3=C(C(=N1)C1=CC=C(C=C1)Cl)C=C(C=C3)OC)=CN(C(C=2)=O)C TVFBIJNOBAXMEN-UHFFFAOYSA-N 0.000 description 1
- UJULDZHZBWSWFE-UHFFFAOYSA-N N-ethyl-2-[9-methoxy-2-methyl-7-(5-methylpyridin-2-yl)-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]acetamide Chemical compound CCNC(=O)CC1OC(c2ccc(C)cn2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 UJULDZHZBWSWFE-UHFFFAOYSA-N 0.000 description 1
- 125000004212 difluorophenyl group Chemical group 0.000 description 1
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| PCT/IN2016/050098 WO2016157221A1 (en) | 2015-03-30 | 2016-03-30 | Tricyclic fused derivatives of 1-(cyclo)alkyl pyridin-2-one useful for the treatment of cancer |
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| US10689395B2 (en) | 2015-09-09 | 2020-06-23 | Jubilant Biosys Limited | Tricyclic fused pyridin-2-one derivatives and their use as BRD4 inhibitors |
| CN108069976A (zh) * | 2016-11-10 | 2018-05-25 | 山东罗欣药业集团股份有限公司 | 一种含氮大环类化合物、其制备方法、药物组合物及应用 |
| WO2019214399A1 (zh) * | 2018-05-10 | 2019-11-14 | 罗欣药业(上海)有限公司 | 苯并七元杂环类化合物、其制备方法、药物组合物及应用 |
| CN110172068A (zh) * | 2019-06-05 | 2019-08-27 | 河南龙湖生物技术有限公司 | 具有抗肿瘤活性的苯并噻唑类化合物及其制备方法和应用 |
| US12527741B2 (en) | 2021-06-17 | 2026-01-20 | Wisconsin Alumni Research Foundation | Modular dendron micelles for treatment of pulmonary diseases related to fibrosis and viral infection including COVID-19 |
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| GB1545767A (en) * | 1976-06-30 | 1979-05-16 | Aspro Nicholas Ltd | Isoquinoline derivatives |
| TW200904403A (en) | 2007-04-25 | 2009-02-01 | Daiichi Sankyo Co Ltd | Tricyclic aryl compounds |
| RU2506267C2 (ru) | 2008-03-31 | 2014-02-10 | Дженентек, Инк. | Бензопирановые и бензоксепиновые ингибиторы рi3k и их применение |
| ES2526671T3 (es) | 2010-06-22 | 2015-01-14 | Glaxosmithkline Llc | Compuestos de benzotriazoldiazepina inhibidores de bromodominios |
| AR084070A1 (es) * | 2010-12-02 | 2013-04-17 | Constellation Pharmaceuticals Inc | Inhibidores del bromodominio y usos de los mismos |
| CA2901352A1 (en) * | 2013-02-19 | 2014-08-28 | Bayer Pharma Aktiengesellschaft | Bicyclo 2,3-benzodiazepines and spirocyclically substituted 2,3-benzodiazepines |
| CN105026403B (zh) | 2013-03-12 | 2018-05-18 | 艾伯维公司 | 四环布罗莫结构域抑制剂 |
| WO2015018520A1 (en) | 2013-08-06 | 2015-02-12 | Oncoethix Sa | A bet-brd inhibitor represents a novel agent for alk positive anaplastic large cell lymphoma |
| US9814728B2 (en) * | 2013-09-20 | 2017-11-14 | Saint Louis University | Inhibition of DUX4 expression using bromodomain and extra-terminal domain protein inhibitors (BETi) |
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