BR112017020739B1 - Compostos fundidos tricíclicos de 1-cicloalquil piridin-2-ona, composição farmacêutica e seus usos - Google Patents

Info

Publication number

BR112017020739B1

BR112017020739B1 BR112017020739-7A BR112017020739A BR112017020739B1 BR 112017020739 B1 BR112017020739 B1 BR 112017020739B1 BR 112017020739 A BR112017020739 A BR 112017020739A BR 112017020739 B1 BR112017020739 B1 BR 112017020739B1

Authority

BR

Brazil

Prior art keywords

oxo

methyl

methoxy

alkyl

pyrido

Prior art date

2015-03-30

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 136
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 16
• UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 title abstract 3
• -1 complexes Chemical class 0.000 claims abstract description 106
• 239000000203 mixture Substances 0.000 claims abstract description 62
• 150000003839 salts Chemical class 0.000 claims abstract description 42
• 206010028980 Neoplasm Diseases 0.000 claims abstract description 33
• 238000011282 treatment Methods 0.000 claims abstract description 19
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
• 239000003814 drug Substances 0.000 claims abstract description 17
• 102000001805 Bromodomains Human genes 0.000 claims abstract description 16
• 201000011510 cancer Diseases 0.000 claims abstract description 16
• 108050009021 Bromodomains Proteins 0.000 claims abstract description 13
• 238000004519 manufacturing process Methods 0.000 claims abstract description 11
• 230000001404 mediated effect Effects 0.000 claims abstract description 3
• 125000003118 aryl group Chemical group 0.000 claims description 118
• 125000001072 heteroaryl group Chemical group 0.000 claims description 118
• 229910052739 hydrogen Inorganic materials 0.000 claims description 100
• 239000001257 hydrogen Substances 0.000 claims description 100
• 125000000217 alkyl group Chemical group 0.000 claims description 75
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 67
• 150000002431 hydrogen Chemical group 0.000 claims description 66
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 65
• 229910003827 NRaRb Inorganic materials 0.000 claims description 60
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 54
• 125000001424 substituent group Chemical group 0.000 claims description 50
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 49
• 229910052736 halogen Inorganic materials 0.000 claims description 47
• 150000002367 halogens Chemical class 0.000 claims description 47
• 125000001188 haloalkyl group Chemical group 0.000 claims description 46
• 125000000623 heterocyclic group Chemical group 0.000 claims description 46
• 239000000460 chlorine Chemical group 0.000 claims description 40
• 125000003545 alkoxy group Chemical group 0.000 claims description 39
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 38
• 239000011737 fluorine Chemical group 0.000 claims description 38
• 229910052731 fluorine Inorganic materials 0.000 claims description 38
• 125000004438 haloalkoxy group Chemical group 0.000 claims description 38
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 37
• 229910052801 chlorine Inorganic materials 0.000 claims description 37
• 125000006696 (C2-C18) heterocyclyl group Chemical group 0.000 claims description 36
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 36
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 35
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 35
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 34
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 34
• 229910052794 bromium Inorganic materials 0.000 claims description 34
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 31
• 125000000000 cycloalkoxy group Chemical group 0.000 claims description 31
• 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 claims description 29
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 29
• 239000000243 solution Substances 0.000 claims description 27
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 25
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 24
• 125000000018 nitroso group Chemical group N(=O)* 0.000 claims description 23
• 125000004043 oxo group Chemical group O=* 0.000 claims description 23
• 125000000464 thioxo group Chemical group S=* 0.000 claims description 23
• 125000005842 heteroatom Chemical group 0.000 claims description 21
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
• 229910052757 nitrogen Inorganic materials 0.000 claims description 19
• 125000003282 alkyl amino group Chemical group 0.000 claims description 17
• 229910052760 oxygen Inorganic materials 0.000 claims description 17
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
• 125000003342 alkenyl group Chemical group 0.000 claims description 14
• 125000000304 alkynyl group Chemical group 0.000 claims description 14
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 14
• 229910052717 sulfur Inorganic materials 0.000 claims description 14
• 125000000468 ketone group Chemical group 0.000 claims description 13
• 229930194542 Keto Natural products 0.000 claims description 12
• 125000002252 acyl group Chemical group 0.000 claims description 12
• 125000004423 acyloxy group Chemical group 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
• PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 12
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 10
• 239000011630 iodine Substances 0.000 claims description 10
• 229910052740 iodine Inorganic materials 0.000 claims description 10
• 239000002253 acid Substances 0.000 claims description 9
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
• KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 8
• WAKMNMXLFATUJF-UHFFFAOYSA-N ethyl 2-[7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]acetate Chemical compound ClC1=CC=C(C=C1)C1C2=C(C3=CN(C(C=C3C(O1)CC(=O)OCC)=O)C)C=CC(=C2)OC WAKMNMXLFATUJF-UHFFFAOYSA-N 0.000 claims description 8
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
• 230000002062 proliferating effect Effects 0.000 claims description 8
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
• 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 7
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([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
• 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
• 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
• 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
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
• 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 5
• 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 description 5
• 229940079593 drug 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
• 230000002401 inhibitory effect Effects 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
• 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
• 125000000335 thiazolyl group Chemical group 0.000 claims description 5
• 125000001544 thienyl group Chemical group 0.000 claims description 5
• 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 claims description 5
• 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
• 125000005843 halogen group Chemical group 0.000 claims description 4
• 230000002265 prevention Effects 0.000 claims description 4
• 125000004306 triazinyl group Chemical group 0.000 claims description 4
• 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 3
• 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 description 3
• XKKJWRPBHOFDIX-RCZVLFRGSA-N 2-[(5R,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-RCZVLFRGSA-N 0.000 claims description 3
• 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 claims description 3
• 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 claims description 3
• 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 3
• 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 3
• 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 claims description 3
• OZDFAPDORADSGG-UHFFFAOYSA-N 2-[7-(4-chloro-2-methylphenyl)-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)cc2C)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 OZDFAPDORADSGG-UHFFFAOYSA-N 0.000 claims description 3
• 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 claims description 3
• 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 3
• SNWQIUCCTFTLIX-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-9-fluoro-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(F)ccc2-c2cn(C)c(=O)cc12 SNWQIUCCTFTLIX-UHFFFAOYSA-N 0.000 claims description 3
• 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 claims description 3
• 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 description 3
• JCAZXVOHALWELW-UHFFFAOYSA-N 4,5-dihydroazepin-3-one Chemical compound O=C1CCC=CN=C1 JCAZXVOHALWELW-UHFFFAOYSA-N 0.000 claims description 3
• JCUHOPOAPQOACK-UHFFFAOYSA-N 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=NC(C=2C(C3=C1C=C(C=C3)OC)=CN(C(C=2)=O)C)C JCUHOPOAPQOACK-UHFFFAOYSA-N 0.000 claims description 3
• 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 3
• 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 3
• JJCKCQFUWGUHNZ-OAQYLSRUSA-N N-ethyl-2-[(5R)-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-OAQYLSRUSA-N 0.000 claims description 3
• 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 3
• 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 description 3
• 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 description 3
• JOWNYTJTMJPZHA-UHFFFAOYSA-N N-ethyl-2-[9-methoxy-2-methyl-3-oxo-7-(trifluoromethyl)-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetamide Chemical compound CCNC(=O)CC1N=C(c2cc(OC)ccc2-c2cn(C)c(=O)cc12)C(F)(F)F JOWNYTJTMJPZHA-UHFFFAOYSA-N 0.000 claims description 3
• PAYRUJLWNCNPSJ-UHFFFAOYSA-N N-phenyl amine Natural products NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 3
• 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 description 3
• 208000035475 disorder Diseases 0.000 claims description 3
• AGTIQMPQYPAYHC-UHFFFAOYSA-N ethyl 2-(7-cyclohexyl-9-methoxy-2-methyl-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl)acetate Chemical compound CCOC(=O)CC1OC(C2CCCCC2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 AGTIQMPQYPAYHC-UHFFFAOYSA-N 0.000 claims description 3
• IUFIUOFDWUBIDJ-UHFFFAOYSA-N ethyl 2-(9-methoxy-2-methyl-3-oxo-7-pyridin-2-yl-5H-pyrido[4,3-d][2]benzazepin-5-yl)acetate Chemical compound CCOC(=O)CC1N=C(c2ccccn2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 IUFIUOFDWUBIDJ-UHFFFAOYSA-N 0.000 claims description 3
• HPLIWSCOGLIXGN-UHFFFAOYSA-N ethyl 2-[7-(2,6-difluorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetate Chemical compound CCOC(=O)CC1N=C(c2cc(OC)ccc2-c2cn(C)c(=O)cc12)c1c(F)cccc1F HPLIWSCOGLIXGN-UHFFFAOYSA-N 0.000 claims description 3
• UOJRVUJPOSPVEE-UHFFFAOYSA-N ethyl 2-[7-(4-chlorophenyl)-9-fluoro-2-methyl-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]acetate Chemical compound CCOC(=O)CC1OC(c2ccc(Cl)cc2)c2cc(F)ccc2-c2cn(C)c(=O)cc12 UOJRVUJPOSPVEE-UHFFFAOYSA-N 0.000 claims description 3
• KYXFLLGSCSQKCR-UHFFFAOYSA-N ethyl 2-[7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetate Chemical compound ClC1=CC=C(C=C1)C1=NC(C=2C(C3=C1C=C(C=C3)OC)=CN(C(C=2)=O)C)CC(=O)OCC KYXFLLGSCSQKCR-UHFFFAOYSA-N 0.000 claims description 3
• NREPESAAXGIQDO-UHFFFAOYSA-N ethyl 2-[7-(4-chlorophenyl)-9-methoxy-3-oxo-2-propan-2-yl-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetate Chemical compound CCOC(=O)CC1N=C(c2ccc(Cl)cc2)c2cc(OC)ccc2-c2cn(C(C)C)c(=O)cc12 NREPESAAXGIQDO-UHFFFAOYSA-N 0.000 claims description 3
• BYCCRNGHSQNLKE-UHFFFAOYSA-N ethyl 2-[7-(cyclopropylmethyl)-9-methoxy-2-methyl-3-oxo-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]acetate Chemical compound CCOC(=O)CC1OC(CC2CC2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 BYCCRNGHSQNLKE-UHFFFAOYSA-N 0.000 claims description 3
• XNMICUIHFXMTFM-UHFFFAOYSA-N ethyl 2-[7-(cyclopropylmethyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetate Chemical compound CCOC(=O)CC1N=C(CC2CC2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 XNMICUIHFXMTFM-UHFFFAOYSA-N 0.000 claims description 3
• FBQICLKLBPUXEY-UHFFFAOYSA-N ethyl 2-[9-methoxy-2-methyl-3-oxo-7-(trifluoromethyl)-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetate Chemical compound CCOC(=O)CC1N=C(c2cc(OC)ccc2-c2cn(C)c(=O)cc12)C(F)(F)F FBQICLKLBPUXEY-UHFFFAOYSA-N 0.000 claims description 3
• JTWXWLQATKQHHX-UHFFFAOYSA-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]acetate Chemical compound CCOC(=O)CC1OC(c2ccc(C)cn2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 JTWXWLQATKQHHX-UHFFFAOYSA-N 0.000 claims description 3
• QPUMIBDVWKXLDZ-UHFFFAOYSA-N ethyl 2-[9-methoxy-2-methyl-7-(5-methylpyridin-2-yl)-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetate Chemical compound CCOC(=O)CC1N=C(c2ccc(C)cn2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 QPUMIBDVWKXLDZ-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
• 239000000725 suspension Substances 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
• JCUHOPOAPQOACK-ZDUSSCGKSA-N (5S)-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-ZDUSSCGKSA-N 0.000 claims description 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
• 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
• 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 description 2
• 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 claims description 2
• 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 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
• 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 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
• 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 claims description 2
• XKKJWRPBHOFDIX-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-9-methoxy-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(OC)ccc2-c2cn(C)c(=O)cc12 XKKJWRPBHOFDIX-UHFFFAOYSA-N 0.000 claims description 2
• SMXNVODKASYVSO-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-(4-hydroxyphenyl)acetamide Chemical compound COc1ccc2-c3cn(C)c(=O)cc3C(CC(=O)Nc3ccc(O)cc3)N=C(c3ccc(Cl)cc3)c2c1 SMXNVODKASYVSO-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
• OVWBTWXDFMHNPE-UHFFFAOYSA-N 2-[7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetamide Chemical compound COc1ccc2-c3cn(C)c(=O)cc3C(CC(N)=O)N=C(c3ccc(Cl)cc3)c2c1 OVWBTWXDFMHNPE-UHFFFAOYSA-N 0.000 claims description 2
• 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 claims description 2
• 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 claims description 2
• 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 claims description 2
• JJCKCQFUWGUHNZ-UHFFFAOYSA-N N-ethyl-2-(9-methoxy-2-methyl-3-oxo-7-pyridin-2-yl-5H-pyrido[4,3-d][2]benzazepin-5-yl)acetamide Chemical compound CCNC(=O)CC1N=C(c2ccccn2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 JJCKCQFUWGUHNZ-UHFFFAOYSA-N 0.000 claims description 2
• MPYNBEBCRUQONH-XUZZJYLKSA-N N-ethyl-2-[(5S,7R)-2-methyl-3-oxo-7-phenyl-9-(trifluoromethyl)-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]acetamide Chemical compound CN1C=C2C(=CC1=O)[C@@H](O[C@@H](C1=C2C=CC(=C1)C(F)(F)F)C1=CC=CC=C1)CC(=O)NCC MPYNBEBCRUQONH-XUZZJYLKSA-N 0.000 claims description 2
• MPYNBEBCRUQONH-URXFXBBRSA-N N-ethyl-2-[(5S,7S)-2-methyl-3-oxo-7-phenyl-9-(trifluoromethyl)-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]acetamide Chemical compound CCNC(=O)C[C@@H]1O[C@@H](c2ccccc2)c2cc(ccc2-c2cn(C)c(=O)cc12)C(F)(F)F MPYNBEBCRUQONH-URXFXBBRSA-N 0.000 claims description 2
• 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 claims description 2
• QZPOULWVADXPLE-UHFFFAOYSA-N N-ethyl-2-[9-methoxy-2-methyl-7-(5-methylpyridin-2-yl)-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetamide Chemical compound CCNC(=O)CC1N=C(c2ccc(C)cn2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 QZPOULWVADXPLE-UHFFFAOYSA-N 0.000 claims description 2
• 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 description 2
• 125000001769 aryl amino group Chemical class 0.000 claims description 2
• 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
• IWYWZPXMNVVJLX-UHFFFAOYSA-N ethyl 2-(7-cyclohexyl-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl)acetate Chemical compound CCOC(=O)CC1N=C(C2CCCCC2)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 IWYWZPXMNVVJLX-UHFFFAOYSA-N 0.000 claims description 2
• PTDWFWSEFSGYTK-UHFFFAOYSA-N ethyl 2-[7-(4-chloro-2-methylphenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetate Chemical compound CCOC(=O)CC1N=C(c2ccc(Cl)cc2C)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 PTDWFWSEFSGYTK-UHFFFAOYSA-N 0.000 claims description 2
• YJWUXOUAYOCCOM-UHFFFAOYSA-N ethyl 2-[7-(4-chlorophenyl)-2-methyl-3-oxo-9-(trifluoromethyl)-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-5-yl]acetate Chemical compound CCOC(=O)CC1OC(c2ccc(Cl)cc2)c2cc(ccc2-c2cn(C)c(=O)cc12)C(F)(F)F YJWUXOUAYOCCOM-UHFFFAOYSA-N 0.000 claims description 2
• GZHMSCXPCJOFNU-UHFFFAOYSA-N ethyl 2-[7-(4-chlorophenyl)-9-fluoro-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]acetate Chemical compound CCOC(=O)CC1N=C(c2ccc(Cl)cc2)c2cc(F)ccc2-c2cn(C)c(=O)cc12 GZHMSCXPCJOFNU-UHFFFAOYSA-N 0.000 claims description 2
• 125000005241 heteroarylamino group Chemical class 0.000 claims description 2
• 239000000843 powder Substances 0.000 claims description 2
• 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
• 239000000443 aerosol Substances 0.000 claims 1
• 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
• 239000002775 capsule Substances 0.000 claims 1
• 239000006188 syrup Substances 0.000 claims 1
• 235000020357 syrup Nutrition 0.000 claims 1
• 239000003826 tablet Substances 0.000 claims 1
• 239000012453 solvate Substances 0.000 abstract description 34
• 150000004677 hydrates Chemical class 0.000 abstract description 30
• 201000010099 disease Diseases 0.000 abstract description 14
• 230000015572 biosynthetic process Effects 0.000 abstract description 12
• 238000003786 synthesis reaction Methods 0.000 abstract description 11
• 230000001093 anti-cancer Effects 0.000 abstract description 6
• 239000004480 active ingredient Substances 0.000 abstract description 5
• 238000012512 characterization method Methods 0.000 abstract description 2
• 150000002391 heterocyclic compounds Chemical class 0.000 abstract description 2
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 94
• 238000005160 1H NMR spectroscopy Methods 0.000 description 46
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
• 238000000034 method Methods 0.000 description 31
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 28
• 239000011541 reaction mixture Substances 0.000 description 27
• 239000007787 solid Substances 0.000 description 24
• 238000000926 separation method Methods 0.000 description 21
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
• 210000004027 cell Anatomy 0.000 description 16
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 15
• 235000019439 ethyl acetate Nutrition 0.000 description 15
• 239000012044 organic layer Substances 0.000 description 15
• 229910052938 sodium sulfate Inorganic materials 0.000 description 15
• 235000011152 sodium sulphate Nutrition 0.000 description 15
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 14
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
• 230000002829 reductive effect Effects 0.000 description 12
• 125000004415 heterocyclylalkyl group Chemical group 0.000 description 11
• 238000006243 chemical reaction Methods 0.000 description 10
• 108091005625 BRD4 Proteins 0.000 description 9
• 102100029895 Bromodomain-containing protein 4 Human genes 0.000 description 9
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
• 239000012267 brine Substances 0.000 description 8
• 125000004432 carbon atom Chemical group C* 0.000 description 8
• 230000000694 effects Effects 0.000 description 8
• 239000012299 nitrogen atmosphere Substances 0.000 description 8
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
• 238000004128 high performance liquid chromatography Methods 0.000 description 7
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
• 108090000623 proteins and genes Proteins 0.000 description 7
• 239000000126 substance Substances 0.000 description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• 108020004414 DNA Proteins 0.000 description 6
• 239000003112 inhibitor Substances 0.000 description 6
• 208000015122 neurodegenerative disease Diseases 0.000 description 6
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
• 108010033040 Histones Proteins 0.000 description 5
• 239000007832 Na2SO4 Substances 0.000 description 5
• 239000003480 eluent Substances 0.000 description 5
• 239000000651 prodrug Substances 0.000 description 5
• 229940002612 prodrug Drugs 0.000 description 5
• 239000002904 solvent Substances 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• 102100033642 Bromodomain-containing protein 3 Human genes 0.000 description 4
• ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical class NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 4
• 101000871851 Homo sapiens Bromodomain-containing protein 3 Proteins 0.000 description 4
• 206010027476 Metastases Diseases 0.000 description 4
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• 238000007792 addition Methods 0.000 description 4
• 125000004122 cyclic group Chemical group 0.000 description 4
• 239000000543 intermediate Substances 0.000 description 4
• 150000002894 organic compounds Chemical class 0.000 description 4
• 230000008569 process Effects 0.000 description 4
• 239000000047 product Substances 0.000 description 4
• 235000018102 proteins Nutrition 0.000 description 4
• 102000004169 proteins and genes Human genes 0.000 description 4
• 150000003254 radicals Chemical class 0.000 description 4
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 3
• 102100029894 Bromodomain testis-specific protein Human genes 0.000 description 3
• 102100033641 Bromodomain-containing protein 2 Human genes 0.000 description 3
• 108091005575 Bromodomain-containing proteins Proteins 0.000 description 3
• 108010077544 Chromatin Proteins 0.000 description 3
• 102000006947 Histones Human genes 0.000 description 3
• 101000794028 Homo sapiens Bromodomain testis-specific protein Proteins 0.000 description 3
• 101000871850 Homo sapiens Bromodomain-containing protein 2 Proteins 0.000 description 3
• 241000124008 Mammalia Species 0.000 description 3
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 3
• KPOFBWMAPORSDV-UHFFFAOYSA-N N-[1-(5-bromo-1-methyl-2-oxopyridin-4-yl)ethyl]-2-methylpropane-2-sulfinamide Chemical compound BrC=1C(=CC(N(C=1)C)=O)C(C)NS(=O)C(C)(C)C KPOFBWMAPORSDV-UHFFFAOYSA-N 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
• 238000003349 alamar blue assay Methods 0.000 description 3
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 3
• 230000004663 cell proliferation Effects 0.000 description 3
• 239000003795 chemical substances by application Substances 0.000 description 3
• 210000003483 chromatin Anatomy 0.000 description 3
• 238000004440 column chromatography Methods 0.000 description 3
• 239000012043 crude product Substances 0.000 description 3
• 239000013078 crystal Substances 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000018109 developmental process Effects 0.000 description 3
• 230000014509 gene expression Effects 0.000 description 3
• 238000002347 injection Methods 0.000 description 3
• 239000007924 injection Substances 0.000 description 3
• 239000010410 layer Substances 0.000 description 3
• 239000001301 oxygen Chemical group 0.000 description 3
• 239000000546 pharmaceutical excipient Substances 0.000 description 3
• 229920006395 saturated elastomer Polymers 0.000 description 3
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
• 235000017557 sodium bicarbonate Nutrition 0.000 description 3
• 239000012279 sodium borohydride Substances 0.000 description 3
• 229910000033 sodium borohydride Inorganic materials 0.000 description 3
• 239000004059 squalene synthase inhibitor Substances 0.000 description 3
• QJSNUWJJESDKLO-UHFFFAOYSA-N tert-butyl N-[[7-(4-chlorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]methyl]carbamate Chemical compound ClC1=CC=C(C=C1)C1=NC(C=2C(C3=C1C=C(C=C3)OC)=CN(C(C=2)=O)C)CNC(OC(C)(C)C)=O QJSNUWJJESDKLO-UHFFFAOYSA-N 0.000 description 3
• 230000004614 tumor growth Effects 0.000 description 3
• KZTWONRVIPPDKH-UHFFFAOYSA-N 2-(piperidin-1-yl)ethanol Chemical class OCCN1CCCCC1 KZTWONRVIPPDKH-UHFFFAOYSA-N 0.000 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 description 2
• DUGXRRQFBUQQPA-UHFFFAOYSA-N 5-(aminomethyl)-7-(4-chlorophenyl)-9-methoxy-2-methyl-5H-pyrido[4,3-d][2]benzazepin-3-one hydrochloride Chemical compound Cl.COc1ccc2-c3cn(C)c(=O)cc3C(CN)N=C(c3ccc(Cl)cc3)c2c1 DUGXRRQFBUQQPA-UHFFFAOYSA-N 0.000 description 2
• HEKMZUSLBDFCKV-UHFFFAOYSA-N 5-bromo-1-methyl-2-oxopyridine-4-carbaldehyde Chemical compound CN1C=C(Br)C(C=O)=CC1=O HEKMZUSLBDFCKV-UHFFFAOYSA-N 0.000 description 2
• ACQXZKFSYFPDIO-UHFFFAOYSA-N 5-bromo-4-(hydroxymethyl)-1-methylpyridin-2-one Chemical compound BrC=1C(=CC(N(C=1)C)=O)CO ACQXZKFSYFPDIO-UHFFFAOYSA-N 0.000 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 description 2
• NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 2
• 241000182988 Assa Species 0.000 description 2
• 208000003174 Brain Neoplasms Diseases 0.000 description 2
• 206010006187 Breast cancer Diseases 0.000 description 2
• 208000026310 Breast neoplasm Diseases 0.000 description 2
• RBUYADASKPIRNA-UHFFFAOYSA-N COC1=CC(C(=O)C2=CC=C(Cl)C=C2)=C(C=C1)B1OC(C)(C)C(C)(C)O1 Chemical compound COC1=CC(C(=O)C2=CC=C(Cl)C=C2)=C(C=C1)B1OC(C)(C)C(C)(C)O1 RBUYADASKPIRNA-UHFFFAOYSA-N 0.000 description 2
• 206010009944 Colon cancer Diseases 0.000 description 2
• 201000004624 Dermatitis Diseases 0.000 description 2
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
• 102000004190 Enzymes Human genes 0.000 description 2
• 108090000790 Enzymes Proteins 0.000 description 2
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 208000002250 Hematologic Neoplasms Diseases 0.000 description 2
• 102000003893 Histone acetyltransferases Human genes 0.000 description 2
• 108090000246 Histone acetyltransferases Proteins 0.000 description 2
• 102000003964 Histone deacetylase Human genes 0.000 description 2
• 108090000353 Histone deacetylase Proteins 0.000 description 2
• 208000008839 Kidney Neoplasms Diseases 0.000 description 2
• 206010058467 Lung neoplasm malignant Diseases 0.000 description 2
• 206010025323 Lymphomas Diseases 0.000 description 2
• OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 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 description 2
• CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Chemical class CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 2
• 208000003788 Neoplasm Micrometastasis Diseases 0.000 description 2
• 108010047956 Nucleosomes Proteins 0.000 description 2
• 108700020796 Oncogene Proteins 0.000 description 2
• 206010033128 Ovarian cancer Diseases 0.000 description 2
• 206010061535 Ovarian neoplasm Diseases 0.000 description 2
• 206010061902 Pancreatic neoplasm Diseases 0.000 description 2
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical class C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
• 206010060862 Prostate cancer Diseases 0.000 description 2
• 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
• 239000012083 RIPA buffer Substances 0.000 description 2
• 206010038389 Renal cancer Diseases 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 208000005718 Stomach Neoplasms Diseases 0.000 description 2
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
• 108091023040 Transcription factor Proteins 0.000 description 2
• 102000040945 Transcription factor Human genes 0.000 description 2
• 230000001154 acute effect Effects 0.000 description 2
• 125000004414 alkyl thio group Chemical group 0.000 description 2
• 229910021529 ammonia Inorganic materials 0.000 description 2
• 150000001448 anilines Chemical class 0.000 description 2
• 229940034982 antineoplastic agent Drugs 0.000 description 2
• 239000002246 antineoplastic agent Substances 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical class NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
• 229910052799 carbon Inorganic materials 0.000 description 2
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
• 238000004296 chiral HPLC Methods 0.000 description 2
• 208000029742 colonic neoplasm Diseases 0.000 description 2
• 238000002648 combination therapy Methods 0.000 description 2
• 229940125904 compound 1 Drugs 0.000 description 2
• 229940125782 compound 2 Drugs 0.000 description 2
• 229940126540 compound 41 Drugs 0.000 description 2
• 229940127089 cytotoxic agent Drugs 0.000 description 2
• 239000002254 cytotoxic agent Substances 0.000 description 2
• 238000010790 dilution Methods 0.000 description 2
• 239000012895 dilution Substances 0.000 description 2
• SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Chemical class CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 2
• RUGPULSVRRIHCK-UHFFFAOYSA-N ethyl 2-(9-methoxy-2,7-dimethyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl)acetate Chemical compound CCOC(=O)CC1N=C(C)c2cc(OC)ccc2-c2cn(C)c(=O)cc12 RUGPULSVRRIHCK-UHFFFAOYSA-N 0.000 description 2
• 230000004927 fusion Effects 0.000 description 2
• 108020001507 fusion proteins Proteins 0.000 description 2
• 102000037865 fusion proteins Human genes 0.000 description 2
• 206010017758 gastric cancer Diseases 0.000 description 2
• 230000012010 growth Effects 0.000 description 2
• 208000014829 head and neck neoplasm Diseases 0.000 description 2
• 201000005787 hematologic cancer Diseases 0.000 description 2
• 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 2
• 230000006195 histone acetylation Effects 0.000 description 2
• 239000005457 ice water Substances 0.000 description 2
• 238000001727 in vivo Methods 0.000 description 2
• 239000004615 ingredient Substances 0.000 description 2
• 150000007529 inorganic bases Chemical class 0.000 description 2
• AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 2
• 201000010982 kidney cancer Diseases 0.000 description 2
• 239000007788 liquid Substances 0.000 description 2
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
• RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 description 2
• 201000005202 lung cancer Diseases 0.000 description 2
• 208000020816 lung neoplasm Diseases 0.000 description 2
• 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 2
• 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 2
• 239000002207 metabolite Substances 0.000 description 2
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
• XOMMLGBSSAVOET-UHFFFAOYSA-N methyl 5-bromo-2-oxo-1h-pyridine-4-carboxylate Chemical compound COC(=O)C1=CC(=O)NC=C1Br XOMMLGBSSAVOET-UHFFFAOYSA-N 0.000 description 2
• 239000004005 microsphere Substances 0.000 description 2
• 230000004048 modification Effects 0.000 description 2
• 238000012986 modification Methods 0.000 description 2
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
• 210000001623 nucleosome Anatomy 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• ATYBXHSAIOKLMG-UHFFFAOYSA-N oxepin Chemical compound O1C=CC=CC=C1 ATYBXHSAIOKLMG-UHFFFAOYSA-N 0.000 description 2
• 201000002528 pancreatic cancer Diseases 0.000 description 2
• 208000008443 pancreatic carcinoma Diseases 0.000 description 2
• 239000002245 particle Substances 0.000 description 2
• 230000000144 pharmacologic effect Effects 0.000 description 2
• 229910052698 phosphorus Inorganic materials 0.000 description 2
• 239000011574 phosphorus Chemical group 0.000 description 2
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
• 230000000069 prophylactic effect Effects 0.000 description 2
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
• LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 description 2
• 230000022532 regulation of transcription, DNA-dependent Effects 0.000 description 2
• 230000001105 regulatory effect Effects 0.000 description 2
• 239000000741 silica gel Substances 0.000 description 2
• 229910002027 silica gel Inorganic materials 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 201000011549 stomach cancer Diseases 0.000 description 2
• 239000011593 sulfur Chemical group 0.000 description 2
• 238000012360 testing method Methods 0.000 description 2
• 210000001550 testis Anatomy 0.000 description 2
• 229940124597 therapeutic agent Drugs 0.000 description 2
• 210000001519 tissue Anatomy 0.000 description 2
• 230000002103 transcriptional effect Effects 0.000 description 2
• 229940086542 triethylamine Drugs 0.000 description 2
• KXCMDNYYHIHDJK-UHFFFAOYSA-N (2-bromo-5-methoxyphenyl)-(4-chlorophenyl)methanol Chemical compound BrC1=C(C=C(C=C1)OC)C(O)C1=CC=C(C=C1)Cl KXCMDNYYHIHDJK-UHFFFAOYSA-N 0.000 description 1
• VDIKTPIPDWEQFN-UHFFFAOYSA-N (2-bromo-5-methoxyphenyl)-(4-chlorophenyl)methanone Chemical compound COC1=CC=C(Br)C(C(=O)C=2C=CC(Cl)=CC=2)=C1 VDIKTPIPDWEQFN-UHFFFAOYSA-N 0.000 description 1
• GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
• QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
• HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 description 1
• YAYXWCNDPUFBHY-AWNIVKPZSA-N (NE)-N-[(5-bromo-1-methyl-2-oxopyridin-4-yl)methylidene]-2-methylpropane-2-sulfinamide Chemical compound BrC=1C(=CC(N(C=1)C)=O)\C=N\S(=O)C(C)(C)C YAYXWCNDPUFBHY-AWNIVKPZSA-N 0.000 description 1
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 1
• DATRPFQNEPLAQE-UHFFFAOYSA-N 1,4-dioxine;hydrochloride Chemical compound Cl.O1C=COC=C1 DATRPFQNEPLAQE-UHFFFAOYSA-N 0.000 description 1
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
• UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
• 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
• RQEUFEKYXDPUSK-UHFFFAOYSA-N 1-phenylethylamine Chemical class CC(N)C1=CC=CC=C1 RQEUFEKYXDPUSK-UHFFFAOYSA-N 0.000 description 1
• 125000006017 1-propenyl group Chemical group 0.000 description 1
• PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 description 1
• TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 1
• NPRYCHLHHVWLQZ-TURQNECASA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynylpurin-8-one Chemical compound NC1=NC=C2N(C(N(C2=N1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C NPRYCHLHHVWLQZ-TURQNECASA-N 0.000 description 1
• 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
• UPHOPMSGKZNELG-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carboxylic acid Chemical class C1=CC=C2C(C(=O)O)=C(O)C=CC2=C1 UPHOPMSGKZNELG-UHFFFAOYSA-N 0.000 description 1
• 125000006020 2-methyl-1-propenyl group Chemical group 0.000 description 1
• 125000006088 2-oxoazepinyl group Chemical group 0.000 description 1
• KPGXRSRHYNQIFN-UHFFFAOYSA-N 2-oxoglutaric acid Chemical class OC(=O)CCC(=O)C(O)=O KPGXRSRHYNQIFN-UHFFFAOYSA-N 0.000 description 1
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
• CNEBPAVBXVMZDW-UHFFFAOYSA-N 4,6-dihydro-[2]benzoxepino[4,5-c][1,2]oxazole Chemical class C1OCC2=CC=CC=C2C2=CON=C12 CNEBPAVBXVMZDW-UHFFFAOYSA-N 0.000 description 1
• 125000005986 4-piperidonyl group Chemical group 0.000 description 1
• XHPVOSNOIWGRQQ-UHFFFAOYSA-N 4-pyridin-2-ylmorpholine Chemical class C1COCCN1C1=CC=CC=N1 XHPVOSNOIWGRQQ-UHFFFAOYSA-N 0.000 description 1
• ZABAWRRZXONVRX-UHFFFAOYSA-N 5,7-dihydro-2H-[2]benzoxepino[5,4-c]pyridin-3-one Chemical compound C=1NC(C=C2C=1C1=C(COC2)C=CC=C1)=O ZABAWRRZXONVRX-UHFFFAOYSA-N 0.000 description 1
• WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 1
• GNMUEVRJHCWKTO-FQEVSTJZSA-N 6h-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetamide, 4-(4-chlorophenyl)-n-(4-hydroxyphenyl)-2,3,9-trimethyl-, (6s)- Chemical compound C([C@@H]1N=C(C2=C(N3C(C)=NN=C31)SC(=C2C)C)C=1C=CC(Cl)=CC=1)C(=O)NC1=CC=C(O)C=C1 GNMUEVRJHCWKTO-FQEVSTJZSA-N 0.000 description 1
• QEZXBKMGLAWOHQ-UHFFFAOYSA-N 7-(4-chlorophenyl)-5-(2-hydroxyethyl)-9-methoxy-2-methyl-5,7-dihydro-[2]benzoxepino[5,4-c]pyridin-3-one Chemical compound ClC1=CC=C(C=C1)C1C2=C(C3=CN(C(C=C3C(O1)CCO)=O)C)C=CC(=C2)OC QEZXBKMGLAWOHQ-UHFFFAOYSA-N 0.000 description 1
• KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
• 102100022900 Actin, cytoplasmic 1 Human genes 0.000 description 1
• 108010085238 Actins Proteins 0.000 description 1
• 208000024893 Acute lymphoblastic leukemia Diseases 0.000 description 1
• 208000026872 Addison Disease Diseases 0.000 description 1
• 201000004384 Alopecia Diseases 0.000 description 1
• 238000012815 AlphaLISA Methods 0.000 description 1
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical class [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
• 239000005695 Ammonium acetate Substances 0.000 description 1
• 108020005544 Antisense RNA Proteins 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 206010003210 Arteriosclerosis Diseases 0.000 description 1
• 201000001320 Atherosclerosis Diseases 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 208000003950 B-cell lymphoma Diseases 0.000 description 1
• MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 1
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 1
• 206010004593 Bile duct cancer Diseases 0.000 description 1
• 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 1
• 208000033222 Biliary cirrhosis primary Diseases 0.000 description 1
• 208000018084 Bone neoplasm Diseases 0.000 description 1
• 108091052242 Bromo- and Extra-Terminal domain (BET) family Proteins 0.000 description 1
• 101100463133 Caenorhabditis elegans pdl-1 gene Proteins 0.000 description 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 208000005623 Carcinogenesis Diseases 0.000 description 1
• 208000024172 Cardiovascular disease Diseases 0.000 description 1
• 206010008342 Cervix carcinoma Diseases 0.000 description 1
• 206010008609 Cholangitis sclerosing Diseases 0.000 description 1
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
• 206010009900 Colitis ulcerative Diseases 0.000 description 1
• 208000011231 Crohn disease Diseases 0.000 description 1
• 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
• 238000010485 C−C bond formation reaction Methods 0.000 description 1
• 101100239628 Danio rerio myca gene Proteins 0.000 description 1
• ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
• XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 206010061825 Duodenal neoplasm Diseases 0.000 description 1
• 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
• 206010016654 Fibrosis Diseases 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 201000005569 Gout Diseases 0.000 description 1
• 239000007818 Grignard reagent Substances 0.000 description 1
• 101710113864 Heat shock protein 90 Proteins 0.000 description 1
• 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 1
• 102000002812 Heat-Shock Proteins Human genes 0.000 description 1
• 108010004889 Heat-Shock Proteins Proteins 0.000 description 1
• 102100039869 Histone H2B type F-S Human genes 0.000 description 1
• 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
• 101001035372 Homo sapiens Histone H2B type F-S Proteins 0.000 description 1
• 208000035150 Hypercholesterolemia Diseases 0.000 description 1
• 206010020751 Hypersensitivity Diseases 0.000 description 1
• 206010068961 Hypo HDL cholesterolaemia Diseases 0.000 description 1
• 206010062767 Hypophysitis Diseases 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• 229940126528 Immuno-Oncology Drug Drugs 0.000 description 1
• 206010061218 Inflammation Diseases 0.000 description 1
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
• XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
• QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
• ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
• 150000000994 L-ascorbates Chemical class 0.000 description 1
• LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 1
• KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
• COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
• 239000005511 L01XE05 - Sorafenib Substances 0.000 description 1
• 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
• 239000005536 L01XE08 - Nilotinib Substances 0.000 description 1
• 239000002145 L01XE14 - Bosutinib Substances 0.000 description 1
• 239000002146 L01XE16 - Crizotinib Substances 0.000 description 1
• KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
• 239000004472 Lysine Substances 0.000 description 1
• 102000002274 Matrix Metalloproteinases Human genes 0.000 description 1
• 108010000684 Matrix Metalloproteinases Proteins 0.000 description 1
• 241000699660 Mus musculus Species 0.000 description 1
• 241000699670 Mus sp. Species 0.000 description 1
• 208000009525 Myocarditis Diseases 0.000 description 1
• 201000002481 Myositis Diseases 0.000 description 1
• YYOMOIDSJBDXGS-UHFFFAOYSA-N N-[1-[5-[2-(4-chlorobenzoyl)-4-methoxyphenyl]-1-methyl-2-oxopyridin-4-yl]ethyl]-2-methylpropane-2-sulfinamide Chemical compound ClC1=CC=C(C(=O)C2=C(C=CC(=C2)OC)C=2C(=CC(N(C=2)C)=O)C(C)NS(=O)C(C)(C)C)C=C1 YYOMOIDSJBDXGS-UHFFFAOYSA-N 0.000 description 1
• 238000005481 NMR spectroscopy Methods 0.000 description 1
• 108010089610 Nuclear Proteins Proteins 0.000 description 1
• 102000007999 Nuclear Proteins Human genes 0.000 description 1
• 208000008589 Obesity Diseases 0.000 description 1
• 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
• 102000043276 Oncogene Human genes 0.000 description 1
• 229910019142 PO4 Inorganic materials 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
• 208000002471 Penile Neoplasms Diseases 0.000 description 1
• 208000009565 Pharyngeal Neoplasms Diseases 0.000 description 1
• 206010034811 Pharyngeal cancer Diseases 0.000 description 1
• 108091000080 Phosphotransferase Proteins 0.000 description 1
• 206010035226 Plasma cell myeloma Diseases 0.000 description 1
• 206010035664 Pneumonia Diseases 0.000 description 1
• 206010035742 Pneumonitis Diseases 0.000 description 1
• 208000012654 Primary biliary cholangitis Diseases 0.000 description 1
• 102000055027 Protein Methyltransferases Human genes 0.000 description 1
• 108700040121 Protein Methyltransferases Proteins 0.000 description 1
• 201000004681 Psoriasis Diseases 0.000 description 1
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
• 102000009572 RNA Polymerase II Human genes 0.000 description 1
• 108010009460 RNA Polymerase II Proteins 0.000 description 1
• 208000015634 Rectal Neoplasms Diseases 0.000 description 1
• 206010038910 Retinitis Diseases 0.000 description 1
• 201000000582 Retinoblastoma Diseases 0.000 description 1
• 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
• 206010039705 Scleritis Diseases 0.000 description 1
• 208000000453 Skin Neoplasms Diseases 0.000 description 1
• 206010041067 Small cell lung cancer Diseases 0.000 description 1
• 206010054184 Small intestine carcinoma Diseases 0.000 description 1
• 108010090804 Streptavidin Proteins 0.000 description 1
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
• 208000000389 T-cell leukemia Diseases 0.000 description 1
• 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 description 1
• 206010042971 T-cell lymphoma Diseases 0.000 description 1
• 208000027585 T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
• JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
• 208000024770 Thyroid neoplasm Diseases 0.000 description 1
• 206010062129 Tongue neoplasm Diseases 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 201000006704 Ulcerative Colitis Diseases 0.000 description 1
• 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 1
• 208000006105 Uterine Cervical Neoplasms Diseases 0.000 description 1
• 206010046851 Uveitis Diseases 0.000 description 1
• 206010047115 Vasculitis Diseases 0.000 description 1
• JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• 206010047642 Vitiligo Diseases 0.000 description 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 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 150000001242 acetic acid derivatives Chemical class 0.000 description 1
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 1
• WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
• 239000012346 acetyl chloride Substances 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
• 125000002015 acyclic group Chemical group 0.000 description 1
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
• ULXXDDBFHOBEHA-CWDCEQMOSA-N afatinib Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-CWDCEQMOSA-N 0.000 description 1
• 229960001686 afatinib Drugs 0.000 description 1
• 229960002833 aflibercept Drugs 0.000 description 1
• 108010081667 aflibercept Proteins 0.000 description 1
• 235000004279 alanine Nutrition 0.000 description 1
• 150000001298 alcohols Chemical class 0.000 description 1
• 125000001931 aliphatic group Chemical group 0.000 description 1
• 150000001338 aliphatic hydrocarbons Chemical group 0.000 description 1
• 208000030961 allergic reaction Diseases 0.000 description 1
• 231100000360 alopecia Toxicity 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
• 235000001014 amino acid Nutrition 0.000 description 1
• 125000005001 aminoaryl group Chemical class 0.000 description 1
• 125000005214 aminoheteroaryl group Chemical class 0.000 description 1
• 235000019257 ammonium acetate Nutrition 0.000 description 1
• 229940043376 ammonium acetate Drugs 0.000 description 1
• 235000019270 ammonium chloride Nutrition 0.000 description 1
• 150000003863 ammonium salts Chemical class 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 125000005427 anthranyl group Chemical group 0.000 description 1
• 230000006907 apoptotic process Effects 0.000 description 1
• ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
• 208000011775 arteriosclerosis disease Diseases 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 208000006673 asthma Diseases 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 208000010668 atopic eczema Diseases 0.000 description 1
• 230000001363 autoimmune Effects 0.000 description 1
• 229960003005 axitinib Drugs 0.000 description 1
• RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-N 0.000 description 1
• 125000002785 azepinyl group Chemical group 0.000 description 1
• 125000002393 azetidinyl group Chemical group 0.000 description 1
• 230000008901 benefit Effects 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
• 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
• 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
• 150000001558 benzoic acid derivatives Chemical class 0.000 description 1
• 125000005872 benzooxazolyl group Chemical group 0.000 description 1
• 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 1
• 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 125000002619 bicyclic group Chemical group 0.000 description 1
• 208000026900 bile duct neoplasm Diseases 0.000 description 1
• 238000010170 biological method Methods 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 239000000090 biomarker Substances 0.000 description 1
• 229950000080 birabresib Drugs 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 150000001642 boronic acid derivatives Chemical class 0.000 description 1
• UBPYILGKFZZVDX-UHFFFAOYSA-N bosutinib Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=CC(OC)=C(OCCCN4CCN(C)CC4)C=C3N=CC=2C#N)=C1Cl UBPYILGKFZZVDX-UHFFFAOYSA-N 0.000 description 1
• 229960003736 bosutinib Drugs 0.000 description 1
• 208000019748 bullous skin disease Diseases 0.000 description 1
• YOMWYEITAAOYEC-UHFFFAOYSA-N butane-2-sulfinamide Chemical compound CCC(C)S(N)=O YOMWYEITAAOYEC-UHFFFAOYSA-N 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
• 229910000024 caesium carbonate Inorganic materials 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• 230000009702 cancer cell proliferation Effects 0.000 description 1
• 230000036952 cancer formation Effects 0.000 description 1
• 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
• 125000002837 carbocyclic group Chemical group 0.000 description 1
• 150000001721 carbon Chemical group 0.000 description 1
• 229910002091 carbon monoxide Inorganic materials 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• 231100000504 carcinogenesis Toxicity 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 239000003054 catalyst Substances 0.000 description 1
• 230000020411 cell activation Effects 0.000 description 1
• 230000024245 cell differentiation Effects 0.000 description 1
• 230000003915 cell function Effects 0.000 description 1
• 238000001516 cell proliferation assay Methods 0.000 description 1
• 230000005754 cellular signaling Effects 0.000 description 1
• 201000010881 cervical cancer Diseases 0.000 description 1
• 230000008859 change Effects 0.000 description 1
• 239000003153 chemical reaction reagent Substances 0.000 description 1
• 238000002512 chemotherapy Methods 0.000 description 1
• 208000006990 cholangiocarcinoma Diseases 0.000 description 1
• OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical class C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
• 229960001231 choline Drugs 0.000 description 1
• 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 208000021668 chronic eosinophilic leukemia Diseases 0.000 description 1
• 208000024207 chronic leukemia Diseases 0.000 description 1
• 201000010903 chronic neutrophilic leukemia Diseases 0.000 description 1
• 208000025302 chronic primary adrenal insufficiency Diseases 0.000 description 1
• 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
• 150000001860 citric acid derivatives Chemical class 0.000 description 1
• 239000003184 complementary RNA Substances 0.000 description 1
• 229940125773 compound 10 Drugs 0.000 description 1
• 229940125797 compound 12 Drugs 0.000 description 1
• 229940125851 compound 27 Drugs 0.000 description 1
• 239000012141 concentrate Substances 0.000 description 1
• 229910052802 copper Inorganic materials 0.000 description 1
• 229960005061 crizotinib Drugs 0.000 description 1
• KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 description 1
• 238000002425 crystallisation Methods 0.000 description 1
• 230000008025 crystallization Effects 0.000 description 1
• 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 1
• XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
• 235000018417 cysteine Nutrition 0.000 description 1
• 229960003067 cystine Drugs 0.000 description 1
• 231100000599 cytotoxic agent Toxicity 0.000 description 1
• 229960002448 dasatinib Drugs 0.000 description 1
• 125000005507 decahydroisoquinolyl group Chemical group 0.000 description 1
• 230000002074 deregulated effect Effects 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
• 239000003085 diluting agent Substances 0.000 description 1
• 238000003113 dilution method Methods 0.000 description 1
• 229910001873 dinitrogen Inorganic materials 0.000 description 1
• 125000005879 dioxolanyl group Chemical group 0.000 description 1
• MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
• 230000006806 disease prevention Effects 0.000 description 1
• 238000004090 dissolution Methods 0.000 description 1
• 208000002173 dizziness Diseases 0.000 description 1
• 238000007876 drug discovery Methods 0.000 description 1
• 238000002651 drug therapy Methods 0.000 description 1
• 201000000312 duodenum cancer Diseases 0.000 description 1
• 230000002526 effect on cardiovascular system Effects 0.000 description 1
• 150000002085 enols Chemical group 0.000 description 1
• XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical class OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 description 1
• 201000004101 esophageal cancer Diseases 0.000 description 1
• LXGPXGPUIYVTIX-SNAWJCMRSA-N ethyl (E)-3-(5-bromo-1-methyl-2-oxopyridin-4-yl)prop-2-enoate Chemical compound CCOC(=O)\C=C\C1=CC(=O)N(C)C=C1Br LXGPXGPUIYVTIX-SNAWJCMRSA-N 0.000 description 1
• QDLCNLDACKNXQH-KPKJPENVSA-N ethyl (E)-3-[5-[2-[(4-chlorophenyl)-hydroxymethyl]-4-methoxyphenyl]-1-methyl-2-oxopyridin-4-yl]prop-2-enoate Chemical compound ClC1=CC=C(C=C1)C(C1=C(C=CC(=C1)OC)C=1C(=CC(N(C=1)C)=O)/C=C/C(=O)OCC)O QDLCNLDACKNXQH-KPKJPENVSA-N 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 230000005284 excitation Effects 0.000 description 1
• 230000007717 exclusion Effects 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 206010016629 fibroma Diseases 0.000 description 1
• 230000004761 fibrosis Effects 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 230000002496 gastric effect Effects 0.000 description 1
• 150000002315 glycerophosphates Chemical class 0.000 description 1
• 239000008187 granular material Substances 0.000 description 1
• 150000004795 grignard reagents Chemical class 0.000 description 1
• 239000001963 growth medium Substances 0.000 description 1
• 201000009277 hairy cell leukemia Diseases 0.000 description 1
• 238000010438 heat treatment Methods 0.000 description 1
• 201000011066 hemangioma Diseases 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 231100000283 hepatitis Toxicity 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002430 hydrocarbons Chemical class 0.000 description 1
• 125000001183 hydrocarbyl group Chemical group 0.000 description 1
• 208000006575 hypertriglyceridemia Diseases 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• ZIPLUEXSCPLCEI-UHFFFAOYSA-N iminomethylideneazanide Chemical compound [NH-]C#N ZIPLUEXSCPLCEI-UHFFFAOYSA-N 0.000 description 1
• 230000002519 immonomodulatory effect Effects 0.000 description 1
• 230000008102 immune modulation Effects 0.000 description 1
• 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
• 208000015181 infectious disease Diseases 0.000 description 1
• 230000004968 inflammatory condition Effects 0.000 description 1
• 230000004054 inflammatory process Effects 0.000 description 1
• 230000028709 inflammatory response Effects 0.000 description 1
• 230000005764 inhibitory process Effects 0.000 description 1
• 238000003402 intramolecular cyclocondensation reaction Methods 0.000 description 1
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 229910052742 iron Inorganic materials 0.000 description 1
• 125000003384 isochromanyl group Chemical group C1(OCCC2=CC=CC=C12)* 0.000 description 1
• 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000005956 isoquinolyl group Chemical group 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
• ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
• 208000017169 kidney disease Diseases 0.000 description 1
• 208000032839 leukemia Diseases 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 230000037356 lipid metabolism Effects 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 201000007270 liver cancer Diseases 0.000 description 1
• 208000014018 liver neoplasm Diseases 0.000 description 1
• 229910052749 magnesium Inorganic materials 0.000 description 1
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
• 150000002688 maleic acid derivatives Chemical class 0.000 description 1
• 230000003211 malignant effect Effects 0.000 description 1
• 208000026037 malignant tumor of neck Diseases 0.000 description 1
• 229910052748 manganese Inorganic materials 0.000 description 1
• 108010082117 matrigel Proteins 0.000 description 1
• 238000005259 measurement Methods 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 201000001441 melanoma Diseases 0.000 description 1
• 238000002844 melting Methods 0.000 description 1
• 230000008018 melting Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 230000009401 metastasis Effects 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• FJPDYKLTAURVRU-UHFFFAOYSA-N methyl 2-amino-5-bromopyridine-4-carboxylate Chemical compound COC(=O)C1=CC(N)=NC=C1Br FJPDYKLTAURVRU-UHFFFAOYSA-N 0.000 description 1
• UBIPNOJMXGEOEN-UHFFFAOYSA-N methyl 5-bromo-1-methyl-2-oxopyridine-4-carboxylate Chemical compound COC(=O)C1=CC(=O)N(C)C=C1Br UBIPNOJMXGEOEN-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• XYBRWUNZRUBCGY-UHFFFAOYSA-N methyl n-(5-bromopyridin-2-yl)carbamate Chemical compound COC(=O)NC1=CC=C(Br)C=N1 XYBRWUNZRUBCGY-UHFFFAOYSA-N 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
• 125000002950 monocyclic group Chemical group 0.000 description 1
• 125000002757 morpholinyl group Chemical group 0.000 description 1
• 230000036457 multidrug resistance Effects 0.000 description 1
• 201000006417 multiple sclerosis Diseases 0.000 description 1
• 201000000050 myeloid neoplasm Diseases 0.000 description 1
• WNYIBZHOMJZDKN-UHFFFAOYSA-N n-(2-acetamidoethyl)acetamide Chemical class CC(=O)NCCNC(C)=O WNYIBZHOMJZDKN-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
• 230000009826 neoplastic cell growth Effects 0.000 description 1
• 201000008383 nephritis Diseases 0.000 description 1
• 208000007538 neurilemmoma Diseases 0.000 description 1
• HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 1
• 229960001346 nilotinib Drugs 0.000 description 1
• 150000002823 nitrates Chemical class 0.000 description 1
• 125000004433 nitrogen atom Chemical group N* 0.000 description 1
• 208000002154 non-small cell lung carcinoma Diseases 0.000 description 1
• 231100000065 noncytotoxic Toxicity 0.000 description 1
• 230000002020 noncytotoxic effect Effects 0.000 description 1
• 125000005485 noradamantyl group Chemical group 0.000 description 1
• 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
• 238000011580 nude mouse model Methods 0.000 description 1
• 235000020824 obesity Nutrition 0.000 description 1
• 125000005060 octahydroindolyl group Chemical group N1(CCC2CCCCC12)* 0.000 description 1
• 125000005061 octahydroisoindolyl group Chemical group C1(NCC2CCCCC12)* 0.000 description 1
• 239000003921 oil Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 201000008482 osteoarthritis Diseases 0.000 description 1
• 229940026778 other chemotherapeutics in atc Drugs 0.000 description 1
• 125000005968 oxazolinyl group Chemical group 0.000 description 1
• 230000003647 oxidation Effects 0.000 description 1
• 238000007254 oxidation reaction Methods 0.000 description 1
• UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
• VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical class OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 1
• 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
• 125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
• 125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
• 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
• 102000020233 phosphotransferase Human genes 0.000 description 1
• 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
• 230000000704 physical effect Effects 0.000 description 1
• 125000004193 piperazinyl group Chemical group 0.000 description 1
• 125000003386 piperidinyl group Chemical group 0.000 description 1
• 125000003367 polycyclic group Chemical group 0.000 description 1
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
• 229920000053 polysorbate 80 Polymers 0.000 description 1
• 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 229910000027 potassium carbonate Inorganic materials 0.000 description 1
• 230000003389 potentiating effect Effects 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 238000002360 preparation method Methods 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
• 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
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
• 125000005493 quinolyl group Chemical group 0.000 description 1
• 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
• 238000001959 radiotherapy Methods 0.000 description 1
• 230000007115 recruitment Effects 0.000 description 1
• 206010038038 rectal cancer Diseases 0.000 description 1
• 201000001275 rectum cancer Diseases 0.000 description 1
• 230000009467 reduction Effects 0.000 description 1
• 230000008844 regulatory mechanism Effects 0.000 description 1
• 238000011160 research Methods 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• 238000012552 review Methods 0.000 description 1
• 206010039073 rheumatoid arthritis Diseases 0.000 description 1
• 150000003873 salicylate salts Chemical class 0.000 description 1
• 206010039667 schwannoma Diseases 0.000 description 1
• 208000010157 sclerosing cholangitis Diseases 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 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
• 229910000029 sodium carbonate Inorganic materials 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
• 229960003787 sorafenib Drugs 0.000 description 1
• 125000003003 spiro group Chemical group 0.000 description 1
• 238000006467 substitution reaction Methods 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• 150000003890 succinate salts Chemical class 0.000 description 1
• 125000005555 sulfoximide group Chemical group 0.000 description 1
• 125000004434 sulfur atom Chemical group 0.000 description 1
• 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
• 235000011149 sulphuric acid Nutrition 0.000 description 1
• 238000001356 surgical procedure Methods 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
• 238000002626 targeted therapy Methods 0.000 description 1
• 150000003892 tartrate salts Chemical class 0.000 description 1
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
• 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
• 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
• 230000001225 therapeutic effect Effects 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical class 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
• 125000006089 thiamorpholinyl sulfoxide group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000002769 thiazolinyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 229930192474 thiophene Natural products 0.000 description 1
• 201000002510 thyroid cancer Diseases 0.000 description 1
• 206010043778 thyroiditis Diseases 0.000 description 1
• 201000006134 tongue cancer Diseases 0.000 description 1
• 125000005490 tosylate group Chemical group 0.000 description 1
• 238000013518 transcription Methods 0.000 description 1
• 230000035897 transcription Effects 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
• 238000000825 ultraviolet detection Methods 0.000 description 1
• 201000005112 urinary bladder cancer Diseases 0.000 description 1
• 230000002792 vascular Effects 0.000 description 1
• 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
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 238000001262 western blot Methods 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1