ES2911886T3 - Derivados condensados tricíclicos de 1-(ciclo)alquilpiridin-2-ona útiles para el tratamiento del cáncer - Google Patents
Derivados condensados tricíclicos de 1-(ciclo)alquilpiridin-2-ona útiles para el tratamiento del cáncer Download PDFInfo
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- ES2911886T3 ES2911886T3 ES16723536T ES16723536T ES2911886T3 ES 2911886 T3 ES2911886 T3 ES 2911886T3 ES 16723536 T ES16723536 T ES 16723536T ES 16723536 T ES16723536 T ES 16723536T ES 2911886 T3 ES2911886 T3 ES 2911886T3
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- Prior art keywords
- oxo
- methyl
- methoxy
- alkyl
- benzo
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- 206010028980 Neoplasm Diseases 0.000 title claims description 35
- 201000011510 cancer Diseases 0.000 title claims description 17
- 238000011282 treatment Methods 0.000 title description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 135
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 123
- 125000003118 aryl group Chemical group 0.000 claims abstract description 114
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 104
- 239000001257 hydrogen Substances 0.000 claims abstract description 104
- -1 amino, hydrazino, formyl Chemical group 0.000 claims abstract description 102
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 90
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 69
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 59
- 229910003827 NRaRb Inorganic materials 0.000 claims abstract description 57
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims abstract description 56
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 50
- 150000002367 halogens Chemical group 0.000 claims abstract description 50
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 48
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 41
- 150000003839 salts Chemical class 0.000 claims abstract description 41
- 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 38
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 37
- 239000012453 solvate Substances 0.000 claims abstract description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 35
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 34
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 33
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 31
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 31
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims abstract description 28
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 26
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 24
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 23
- 125000000464 thioxo group Chemical group S=* 0.000 claims abstract description 23
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims abstract description 22
- 125000000018 nitroso group Chemical group N(=O)* 0.000 claims abstract description 22
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 17
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 15
- 150000002431 hydrogen Chemical group 0.000 claims abstract 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 138
- 239000000203 mixture Substances 0.000 claims description 62
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 56
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 54
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 51
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 51
- 125000001424 substituent group Chemical group 0.000 claims description 48
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 37
- 239000000460 chlorine Chemical group 0.000 claims description 37
- 239000011737 fluorine Chemical group 0.000 claims description 37
- 229910052731 fluorine Inorganic materials 0.000 claims description 37
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 36
- 229910052801 chlorine Inorganic materials 0.000 claims description 36
- 238000000034 method Methods 0.000 claims description 34
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 33
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 33
- 229910052794 bromium Inorganic materials 0.000 claims description 33
- 150000004677 hydrates Chemical class 0.000 claims description 30
- 125000006696 (C2-C18) heterocyclyl group Chemical group 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 125000005842 heteroatom Chemical group 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- 102000001805 Bromodomains Human genes 0.000 claims description 15
- 239000011630 iodine Chemical group 0.000 claims description 15
- 229910052740 iodine Inorganic materials 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 108050009021 Bromodomains Proteins 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- 201000010099 disease Diseases 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 12
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 12
- 125000000468 ketone group Chemical group 0.000 claims description 12
- 229930194542 Keto Natural products 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 125000004423 acyloxy group Chemical group 0.000 claims description 11
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 11
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 10
- JCAZXVOHALWELW-UHFFFAOYSA-N 4,5-dihydroazepin-3-one Chemical compound O=C1CCC=CN=C1 JCAZXVOHALWELW-UHFFFAOYSA-N 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
- 230000002062 proliferating effect Effects 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
- 208000035475 disorder Diseases 0.000 claims description 7
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 7
- 229940124530 sulfonamide Drugs 0.000 claims description 7
- 150000003456 sulfonamides Chemical class 0.000 claims description 7
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 7
- NZKFFGZDNRWTTP-UHFFFAOYSA-N azidocyanamide Chemical compound [N-]=[N+]=NNC#N NZKFFGZDNRWTTP-UHFFFAOYSA-N 0.000 claims description 6
- 235000010290 biphenyl Nutrition 0.000 claims description 6
- 239000004305 biphenyl Substances 0.000 claims description 6
- 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 description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 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 description 6
- 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 description 6
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 6
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 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 description 6
- 125000001147 pentyl group Chemical group C(CCCC)* 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 6
- 229910052717 sulfur Inorganic materials 0.000 claims description 6
- 229940127089 cytotoxic agent Drugs 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000002883 imidazolyl group Chemical group 0.000 claims description 5
- 125000001041 indolyl group Chemical group 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 125000002971 oxazolyl group Chemical group 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 241000124008 Mammalia Species 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 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 description 4
- 239000002254 cytotoxic agent Substances 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 125000000335 thiazolyl group Chemical group 0.000 claims description 4
- 125000004306 triazinyl group Chemical group 0.000 claims description 4
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 3
- PMDCZENCAXMSOU-UHFFFAOYSA-N N-Ethylacetamide Natural products CCNC(C)=O PMDCZENCAXMSOU-UHFFFAOYSA-N 0.000 claims description 3
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 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 claims description 2
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 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 claims description 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 description 2
- JOWNYTJTMJPZHA-MRXNPFEDSA-N N-ethyl-2-[(5R)-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-MRXNPFEDSA-N 0.000 claims description 2
- 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 description 2
- JJCKCQFUWGUHNZ-NRFANRHFSA-N N-ethyl-2-[(5S)-9-methoxy-2-methyl-3-oxo-7-pyridin-2-yl-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)C2=NC=CC=C2)C=1 JJCKCQFUWGUHNZ-NRFANRHFSA-N 0.000 claims description 2
- 231100000599 cytotoxic agent Toxicity 0.000 claims description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
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- 125000006000 trichloroethyl group Chemical group 0.000 claims description 2
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 2
- SHXBYXOWMVQGNL-UHFFFAOYSA-N 2-(9-methoxy-2,7-dimethyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl)acetic acid Chemical compound COc1ccc2-c3cn(C)c(=O)cc3C(CC(O)=O)N=C(C)c2c1 SHXBYXOWMVQGNL-UHFFFAOYSA-N 0.000 claims 1
- SMXNVODKASYVSO-AREMUKBSSA-N 2-[(5R)-7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-(4-hydroxyphenyl)acetamide 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)NC1=CC=C(C=C1)O SMXNVODKASYVSO-AREMUKBSSA-N 0.000 claims 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 claims 1
- SMXNVODKASYVSO-SANMLTNESA-N 2-[(5S)-7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-(4-hydroxyphenyl)acetamide 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)NC1=CC=C(C=C1)O SMXNVODKASYVSO-SANMLTNESA-N 0.000 claims 1
- 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 1
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- 238000000338 in vitro Methods 0.000 claims 1
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- GQPLMRYTRLFLPF-UHFFFAOYSA-N nitrous oxide Inorganic materials [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 claims 1
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- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
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- 208000008494 pericarditis Diseases 0.000 description 1
- 238000011422 pharmacological therapy Methods 0.000 description 1
- 125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
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- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
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- 125000004193 piperazinyl group Chemical group 0.000 description 1
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- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
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- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
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- 239000002243 precursor Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 238000000751 protein extraction Methods 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
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- 238000010898 silica gel chromatography Methods 0.000 description 1
- 201000000849 skin cancer Diseases 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- 229960003787 sorafenib Drugs 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
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- 150000003462 sulfoxides Chemical class 0.000 description 1
- 125000005555 sulfoximide group Chemical group 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
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- 230000001629 suppression Effects 0.000 description 1
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
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- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
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- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
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- 201000002510 thyroid cancer Diseases 0.000 description 1
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- 125000005490 tosylate group Chemical group 0.000 description 1
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- 230000035897 transcription Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 201000005112 urinary bladder cancer Diseases 0.000 description 1
- 201000009825 uterine corpus cancer Diseases 0.000 description 1
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- 238000001845 vibrational spectrum Methods 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1636CH2015 | 2015-03-30 | ||
| 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2911886T3 true ES2911886T3 (es) | 2022-05-23 |
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| ES16723536T Active ES2911886T3 (es) | 2015-03-30 | 2016-03-30 | Derivados condensados tricíclicos de 1-(ciclo)alquilpiridin-2-ona útiles para el tratamiento del cáncer |
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| EP (1) | EP3277683B1 (https=) |
| JP (1) | JP6764877B2 (https=) |
| KR (1) | KR102588109B1 (https=) |
| CN (1) | CN107548393B (https=) |
| AU (1) | AU2016242473B2 (https=) |
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| MX (1) | MX376112B (https=) |
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| PT (1) | PT3277683T (https=) |
| RU (1) | RU2721120C2 (https=) |
| WO (1) | WO2016157221A1 (https=) |
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| SMT202100277T1 (it) * | 2015-09-09 | 2021-07-12 | Jubilant Biosys Ltd | Derivati triciclici fusi di piridina-2-0ne e loro uso come inibitori di brd4 |
| CA3045855A1 (en) * | 2016-11-10 | 2018-05-17 | Shandong Luoxin Pharmaceutical Group Stock Co., Ltd. | Nitrogenous macrocyclic compound, preparation method therefor, pharmaceutical composition and application thereof |
| 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 |
| WO2008133288A1 (ja) | 2007-04-25 | 2008-11-06 | Daiichi Sankyo Company, Limited | 三環性アリール化合物 |
| ES2480994T3 (es) | 2008-03-31 | 2014-07-29 | Genentech, Inc. | Compuestos de tipo benzopirano y benzoxepina inhibidores de PI3K y métodos de uso |
| US9085582B2 (en) | 2010-06-22 | 2015-07-21 | Glaxosmithkline Llc | Benzotriazolodiazepine compounds inhibitors of bromodomains |
| 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 |
| WO2014139324A1 (en) * | 2013-03-12 | 2014-09-18 | Abbvie Inc. | Tetracyclic bromodomain inhibitors |
| 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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| EP3277683B1 (en) | 2022-03-09 |
| JP2018510203A (ja) | 2018-04-12 |
| NZ735972A (en) | 2024-08-30 |
| KR102588109B1 (ko) | 2023-10-12 |
| AU2016242473A1 (en) | 2017-10-26 |
| DK3277683T3 (en) | 2022-05-02 |
| PL3277683T3 (pl) | 2022-05-23 |
| CN107548393A (zh) | 2018-01-05 |
| US11319326B2 (en) | 2022-05-03 |
| RU2017135205A (ru) | 2019-04-10 |
| BR112017020739A2 (pt) | 2018-07-17 |
| PT3277683T (pt) | 2022-06-28 |
| CN107548393B (zh) | 2021-03-02 |
| MX376112B (es) | 2025-03-07 |
| IL254528B (en) | 2020-11-30 |
| EP3277683A1 (en) | 2018-02-07 |
| IL254528A0 (en) | 2017-11-30 |
| RU2017135205A3 (https=) | 2019-07-17 |
| RU2721120C2 (ru) | 2020-05-15 |
| BR112017020739B1 (pt) | 2023-03-14 |
| US20200331926A1 (en) | 2020-10-22 |
| US20180282345A1 (en) | 2018-10-04 |
| CA2980266A1 (en) | 2016-10-06 |
| JP6764877B2 (ja) | 2020-10-07 |
| US10689390B2 (en) | 2020-06-23 |
| AU2016242473B2 (en) | 2020-06-25 |
| HK1248686A1 (zh) | 2018-10-19 |
| MX2017012387A (es) | 2018-06-11 |
| KR20170132278A (ko) | 2017-12-01 |
| WO2016157221A1 (en) | 2016-10-06 |
| CA2980266C (en) | 2025-05-06 |
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