CA2910873A1 - Enhancer of zeste homolog 2 inhibitors - Google Patents
Enhancer of zeste homolog 2 inhibitorsInfo
- Publication number
- CA2910873A1 CA2910873A1 CA2910873A CA2910873A CA2910873A1 CA 2910873 A1 CA2910873 A1 CA 2910873A1 CA 2910873 A CA2910873 A CA 2910873A CA 2910873 A CA2910873 A CA 2910873A CA 2910873 A1 CA2910873 A1 CA 2910873A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- methyl
- oxo
- dihydropyridin
- carboxamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 239000003112 inhibitor Substances 0.000 title abstract description 25
- 102000058017 Enhancer of Zeste Homolog 2 Human genes 0.000 title abstract description 24
- 101710196274 Histone-lysine N-methyltransferase EZH2 Proteins 0.000 title abstract description 24
- 150000001875 compounds Chemical class 0.000 claims abstract description 230
- 238000011282 treatment Methods 0.000 claims abstract description 51
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 49
- 238000000034 method Methods 0.000 claims abstract description 43
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
- 238000002360 preparation method Methods 0.000 claims abstract description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 266
- -1 -NR a Rb Chemical group 0.000 claims description 134
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 128
- 125000001072 heteroaryl group Chemical group 0.000 claims description 120
- 125000003118 aryl group Chemical group 0.000 claims description 109
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 98
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 85
- 239000001257 hydrogen Substances 0.000 claims description 83
- 229910052739 hydrogen Inorganic materials 0.000 claims description 83
- 125000003545 alkoxy group Chemical group 0.000 claims description 81
- 229910052736 halogen Inorganic materials 0.000 claims description 78
- 150000002367 halogens Chemical class 0.000 claims description 78
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 76
- 150000003839 salts Chemical class 0.000 claims description 76
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 75
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 72
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 61
- 125000005843 halogen group Chemical group 0.000 claims description 58
- DAUYIKBTMNZABP-UHFFFAOYSA-N thiophene-3-carboxamide Chemical compound NC(=O)C=1C=CSC=1 DAUYIKBTMNZABP-UHFFFAOYSA-N 0.000 claims description 57
- 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 56
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 54
- 229910052757 nitrogen Inorganic materials 0.000 claims description 50
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 46
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 33
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 229910052717 sulfur Inorganic materials 0.000 claims description 31
- 229910052760 oxygen Inorganic materials 0.000 claims description 28
- 201000011510 cancer Diseases 0.000 claims description 25
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 22
- 229920006395 saturated elastomer Polymers 0.000 claims description 20
- 125000005842 heteroatom Chemical group 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 17
- 239000011593 sulfur Chemical group 0.000 claims description 17
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 239000000460 chlorine Chemical group 0.000 claims description 16
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 229910052801 chlorine Chemical group 0.000 claims description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 125000003386 piperidinyl group Chemical group 0.000 claims description 15
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 14
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 claims description 14
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 14
- 206010025323 Lymphomas Diseases 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- 206010039491 Sarcoma Diseases 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 8
- 125000002757 morpholinyl group Chemical group 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 210000000481 breast Anatomy 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
- 208000035475 disorder Diseases 0.000 claims description 7
- 125000002541 furyl group Chemical group 0.000 claims description 7
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 7
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000001425 triazolyl group Chemical group 0.000 claims description 7
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 210000004072 lung Anatomy 0.000 claims description 5
- 210000002307 prostate Anatomy 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 5
- 210000003932 urinary bladder Anatomy 0.000 claims description 5
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 4
- 208000008383 Wilms tumor Diseases 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 210000001072 colon Anatomy 0.000 claims description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 4
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 4
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 4
- 230000002496 gastric effect Effects 0.000 claims description 4
- 208000005017 glioblastoma Diseases 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 206010018338 Glioma Diseases 0.000 claims description 3
- 210000004556 brain Anatomy 0.000 claims description 3
- 239000011737 fluorine Chemical group 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 210000003128 head Anatomy 0.000 claims description 3
- 208000032839 leukemia Diseases 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- 210000003739 neck Anatomy 0.000 claims description 3
- 201000008968 osteosarcoma Diseases 0.000 claims description 3
- 125000003566 oxetanyl group Chemical group 0.000 claims description 3
- 201000009410 rhabdomyosarcoma Diseases 0.000 claims description 3
- QSOIBYJLZBCBBB-UHFFFAOYSA-N 5-[ethyl(oxan-4-yl)amino]-4-methyl-n-[[6-methyl-2-oxo-4-(trifluoromethyl)-1h-pyridin-3-yl]methyl]thiophene-3-carboxamide Chemical compound S1C=C(C(=O)NCC=2C(NC(C)=CC=2C(F)(F)F)=O)C(C)=C1N(CC)C1CCOCC1 QSOIBYJLZBCBBB-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- SMXOJCJHWCTJOO-QAQDUYKDSA-N CN([C@@H]1CC[C@H](CC1)N(C1=C(C(=CS1)C(=O)NCC=1C(NC(=CC1C)C(F)(F)F)=O)C)CC)C Chemical compound CN([C@@H]1CC[C@H](CC1)N(C1=C(C(=CS1)C(=O)NCC=1C(NC(=CC1C)C(F)(F)F)=O)C)CC)C SMXOJCJHWCTJOO-QAQDUYKDSA-N 0.000 claims description 2
- 206010014967 Ependymoma Diseases 0.000 claims description 2
- 208000006168 Ewing Sarcoma Diseases 0.000 claims description 2
- 208000000172 Medulloblastoma Diseases 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Chemical group 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 230000002611 ovarian Effects 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 168
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 52
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 36
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 12
- 125000004043 oxo group Chemical group O=* 0.000 claims 12
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 7
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 7
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 3
- 208000008770 Multiple Hamartoma Syndrome Diseases 0.000 claims 3
- XHROKJJCFRMCBT-UHFFFAOYSA-N 5-[[4-(dimethylamino)cyclohexyl]-ethylamino]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide Chemical compound S1C=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C(C)=C1N(CC)C1CCC(N(C)C)CC1 XHROKJJCFRMCBT-UHFFFAOYSA-N 0.000 claims 2
- IDUHGUNBWPHVAI-YOFSQIOKSA-N CC1=C(C(NC(=C1)C)=O)CNC(=O)C1=CSC(=C1C)C(CC)[C@@H]1CC[C@@H](CC1)N(C)C Chemical compound CC1=C(C(NC(=C1)C)=O)CNC(=O)C1=CSC(=C1C)C(CC)[C@@H]1CC[C@@H](CC1)N(C)C IDUHGUNBWPHVAI-YOFSQIOKSA-N 0.000 claims 2
- 201000002847 Cowden syndrome Diseases 0.000 claims 2
- FOOXUZRFPGZBNI-UHFFFAOYSA-N 2-bromo-5-(diethylamino)-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide Chemical compound CC1=C(N(CC)CC)SC(Br)=C1C(=O)NCC1=C(C)C=C(C)NC1=O FOOXUZRFPGZBNI-UHFFFAOYSA-N 0.000 claims 1
- XVRVJNZQOATEAP-UHFFFAOYSA-N 2-bromo-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-5-[ethyl(oxan-4-yl)amino]-4-methylthiophene-3-carboxamide Chemical compound S1C(Br)=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C(C)=C1N(CC)C1CCOCC1 XVRVJNZQOATEAP-UHFFFAOYSA-N 0.000 claims 1
- VPWRXOUDVYAELQ-UHFFFAOYSA-N 2-chloro-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-5-[ethyl(oxan-4-yl)amino]-4-methylthiophene-3-carboxamide Chemical compound S1C(Cl)=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C(C)=C1N(CC)C1CCOCC1 VPWRXOUDVYAELQ-UHFFFAOYSA-N 0.000 claims 1
- FRTKPKWRJMIGMN-UHFFFAOYSA-N 2-cyano-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-5-[ethyl(oxan-4-yl)amino]-4-methylthiophene-3-carboxamide Chemical compound S1C(C#N)=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C(C)=C1N(CC)C1CCOCC1 FRTKPKWRJMIGMN-UHFFFAOYSA-N 0.000 claims 1
- LVGCTQDARMZPSW-OAQYLSRUSA-N 5-[(1r)-1-[4-(dimethylamino)piperidin-1-yl]propyl]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide Chemical compound N1([C@H](CC)C2=C(C(C(=O)NCC=3C(NC(C)=CC=3C)=O)=CS2)C)CCC(N(C)C)CC1 LVGCTQDARMZPSW-OAQYLSRUSA-N 0.000 claims 1
- LVGCTQDARMZPSW-NRFANRHFSA-N 5-[(1s)-1-[4-(dimethylamino)piperidin-1-yl]propyl]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide Chemical compound N1([C@@H](CC)C2=C(C(C(=O)NCC=3C(NC(C)=CC=3C)=O)=CS2)C)CCC(N(C)C)CC1 LVGCTQDARMZPSW-NRFANRHFSA-N 0.000 claims 1
- LZBICHWHSABGJQ-YXSASFKJSA-N 5-[(z)-6-[4-(dimethylamino)piperidin-1-yl]hex-2-en-3-yl]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide Chemical compound S1C=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C(C)=C1C(=C/C)\CCCN1CCC(N(C)C)CC1 LZBICHWHSABGJQ-YXSASFKJSA-N 0.000 claims 1
- OCVFHWCDYDBBRP-UHFFFAOYSA-N 5-[1-[4-(dimethylamino)piperidin-1-yl]ethyl]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide Chemical compound S1C=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C(C)=C1C(C)N1CCC(N(C)C)CC1 OCVFHWCDYDBBRP-UHFFFAOYSA-N 0.000 claims 1
- MMBRIKLEHZRKNB-UHFFFAOYSA-N 5-[1-[4-(dimethylamino)piperidin-1-yl]ethyl]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]thiophene-3-carboxamide Chemical compound C=1C(C(=O)NCC=2C(NC(C)=CC=2C)=O)=CSC=1C(C)N1CCC(N(C)C)CC1 MMBRIKLEHZRKNB-UHFFFAOYSA-N 0.000 claims 1
- LVGCTQDARMZPSW-UHFFFAOYSA-N 5-[1-[4-(dimethylamino)piperidin-1-yl]propyl]-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide Chemical compound S1C=C(C(=O)NCC=2C(NC(C)=CC=2C)=O)C(C)=C1C(CC)N1CCC(N(C)C)CC1 LVGCTQDARMZPSW-UHFFFAOYSA-N 0.000 claims 1
- KCXYXNRPRRXYDO-UHFFFAOYSA-N 5-[[4-(dimethylamino)cyclohexyl]-ethylamino]-4-methyl-n-[(6-methyl-2-oxo-4-propyl-1h-pyridin-3-yl)methyl]thiophene-3-carboxamide Chemical compound C1=C(C)NC(=O)C(CNC(=O)C=2C(=C(N(CC)C3CCC(CC3)N(C)C)SC=2)C)=C1CCC KCXYXNRPRRXYDO-UHFFFAOYSA-N 0.000 claims 1
- VSNXIWYGHMHREB-UHFFFAOYSA-N 5-[ethyl(oxan-4-yl)amino]-4-methyl-n-[(1,4,6-trimethyl-2-oxopyridin-3-yl)methyl]thiophene-3-carboxamide Chemical compound S1C=C(C(=O)NCC=2C(N(C)C(C)=CC=2C)=O)C(C)=C1N(CC)C1CCOCC1 VSNXIWYGHMHREB-UHFFFAOYSA-N 0.000 claims 1
- PIUDMQZOXJMZKR-UHFFFAOYSA-N 5-chloro-n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-4-[ethyl(oxan-4-yl)amino]-3-methylthiophene-2-carboxamide Chemical compound ClC=1SC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C(C)C=1N(CC)C1CCOCC1 PIUDMQZOXJMZKR-UHFFFAOYSA-N 0.000 claims 1
- 201000007815 Bannayan-Riley-Ruvalcaba syndrome Diseases 0.000 claims 1
- DULCDCQEAIHKPM-IYARVYRRSA-N BrC=1SC(=C(C1C(=O)NCC=1C(NC(=CC1C)C)=O)C)N(CC)[C@@H]1CC[C@H](CC1)N(C)C Chemical compound BrC=1SC(=C(C1C(=O)NCC=1C(NC(=CC1C)C)=O)C)N(CC)[C@@H]1CC[C@H](CC1)N(C)C DULCDCQEAIHKPM-IYARVYRRSA-N 0.000 claims 1
- LLXDKFMURVBHJV-IWZNKUOBSA-N CC1=C(C(NC(=C1)C)=O)CNC(=O)C1=CSC(=C1C)C(O)[C@@H]1CC[C@H](CC1)N(C)C Chemical compound CC1=C(C(NC(=C1)C)=O)CNC(=O)C1=CSC(=C1C)C(O)[C@@H]1CC[C@H](CC1)N(C)C LLXDKFMURVBHJV-IWZNKUOBSA-N 0.000 claims 1
- ZOZZQJIESSTKJX-MXVIHJGJSA-N CC1=C(C(NC(=C1)C)=O)CNC(=O)C=1C(=C(SC1)C(=CC)[C@@H]1CC[C@H](CC1)NC(OC(C)(C)C)=O)C Chemical compound CC1=C(C(NC(=C1)C)=O)CNC(=O)C=1C(=C(SC1)C(=CC)[C@@H]1CC[C@H](CC1)NC(OC(C)(C)C)=O)C ZOZZQJIESSTKJX-MXVIHJGJSA-N 0.000 claims 1
- OEOBFVJMSOTVQD-KDURUIRLSA-N CC1=C(C(NC(=C1)C)=O)CNC(=O)C=1SC=C(C1C)N(CC)[C@@H]1CC[C@@H](CC1)N(C)C Chemical compound CC1=C(C(NC(=C1)C)=O)CNC(=O)C=1SC=C(C1C)N(CC)[C@@H]1CC[C@@H](CC1)N(C)C OEOBFVJMSOTVQD-KDURUIRLSA-N 0.000 claims 1
- OEOBFVJMSOTVQD-WGSAOQKQSA-N CC1=C(C(NC(=C1)C)=O)CNC(=O)C=1SC=C(C1C)N(CC)[C@@H]1CC[C@H](CC1)N(C)C Chemical compound CC1=C(C(NC(=C1)C)=O)CNC(=O)C=1SC=C(C1C)N(CC)[C@@H]1CC[C@H](CC1)N(C)C OEOBFVJMSOTVQD-WGSAOQKQSA-N 0.000 claims 1
- IDUHGUNBWPHVAI-ORXZLVCASA-N CCC([C@H]1CC[C@@H](CC1)N(C)C)c1scc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C Chemical compound CCC([C@H]1CC[C@@H](CC1)N(C)C)c1scc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C IDUHGUNBWPHVAI-ORXZLVCASA-N 0.000 claims 1
- LQRSUXVZQNCRKZ-JHJOSGQCSA-N CCC([C@H]1CC[C@H](N)CC1)c1scc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C Chemical compound CCC([C@H]1CC[C@H](N)CC1)c1scc(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C LQRSUXVZQNCRKZ-JHJOSGQCSA-N 0.000 claims 1
- ANOOOFTUEHAIIC-HZCBDIJESA-N CCN([C@H]1CC[C@@H](CC1)N(C)C)c1sc(-c2ccoc2)c(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C Chemical compound CCN([C@H]1CC[C@@H](CC1)N(C)C)c1sc(-c2ccoc2)c(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C ANOOOFTUEHAIIC-HZCBDIJESA-N 0.000 claims 1
- XXQHACAXRPGDPN-WGSAOQKQSA-N CCN([C@H]1CC[C@@H](CC1)N(C)C)c1sc(C#N)c(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C Chemical compound CCN([C@H]1CC[C@@H](CC1)N(C)C)c1sc(C#N)c(C(=O)NCc2c(C)cc(C)[nH]c2=O)c1C XXQHACAXRPGDPN-WGSAOQKQSA-N 0.000 claims 1
- OPQWDNJKKMJJBB-IYARVYRRSA-N CN([C@@H]1CC[C@H](CC1)N(C1=C(C(=CS1)C(=O)NCC=1C(NC(=CC1OC)C)=O)C)CC)C Chemical compound CN([C@@H]1CC[C@H](CC1)N(C1=C(C(=CS1)C(=O)NCC=1C(NC(=CC1OC)C)=O)C)CC)C OPQWDNJKKMJJBB-IYARVYRRSA-N 0.000 claims 1
- 208000012609 Cowden disease Diseases 0.000 claims 1
- 208000002966 Giant Cell Tumor of Bone Diseases 0.000 claims 1
- 102100038970 Histone-lysine N-methyltransferase EZH2 Human genes 0.000 claims 1
- 101000882127 Homo sapiens Histone-lysine N-methyltransferase EZH2 Proteins 0.000 claims 1
- 208000005726 Inflammatory Breast Neoplasms Diseases 0.000 claims 1
- 206010021980 Inflammatory carcinoma of the breast Diseases 0.000 claims 1
- 208000022010 Lhermitte-Duclos disease Diseases 0.000 claims 1
- JMYOSDLLACUDBE-QAQDUYKDSA-N N[C@@H]1CC[C@H](CC1)/C(=CC)/C1=C(C(=CS1)C(=O)NCC=1C(NC(=CC1C)C)=O)C Chemical compound N[C@@H]1CC[C@H](CC1)/C(=CC)/C1=C(C(=CS1)C(=O)NCC=1C(NC(=CC1C)C)=O)C JMYOSDLLACUDBE-QAQDUYKDSA-N 0.000 claims 1
- SELHOZRPYAMUKI-OSPTYYIOSA-N N[C@@H]1CC[C@H](CC1)C(C1=C(C(=CS1)C(=O)NCC=1C(NC(=CC1C)C)=O)C)O Chemical compound N[C@@H]1CC[C@H](CC1)C(C1=C(C(=CS1)C(=O)NCC=1C(NC(=CC1C)C)=O)C)O SELHOZRPYAMUKI-OSPTYYIOSA-N 0.000 claims 1
- 201000011143 bone giant cell tumor Diseases 0.000 claims 1
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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| US201361817436P | 2013-04-30 | 2013-04-30 | |
| US61/817,436 | 2013-04-30 | ||
| US201361842038P | 2013-07-02 | 2013-07-02 | |
| US61/842,038 | 2013-07-02 | ||
| US201361907024P | 2013-11-21 | 2013-11-21 | |
| US61/907,024 | 2013-11-21 | ||
| US201461936460P | 2014-02-06 | 2014-02-06 | |
| US61/936,460 | 2014-02-06 | ||
| PCT/IB2014/061012 WO2014177982A1 (en) | 2013-04-30 | 2014-04-25 | Enhancer of zeste homolog 2 inhibitors |
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| CN (1) | CN105308038B (enExample) |
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| HK (1) | HK1214815A1 (enExample) |
| MX (1) | MX2015015144A (enExample) |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2021035194A1 (en) | 2019-08-22 | 2021-02-25 | Juno Therapeutics, Inc. | Combination therapy of a t cell therapy and an enhancer of zeste homolog 2 (ezh2) inhibitor and related methods |
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| CA2862289C (en) * | 2012-02-10 | 2019-11-26 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| KR102021642B1 (ko) | 2012-10-15 | 2019-09-16 | 에피자임, 인코포레이티드 | 암을 치료하는 방법 |
| US9505745B2 (en) * | 2013-04-30 | 2016-11-29 | Glaxosmithkline Intellectual Property (No. 2) Limited | Enhancer of zeste homolog 2 inhibitors |
| EP3019494B1 (en) | 2013-07-10 | 2017-06-21 | Glaxosmithkline Intellectual Property (No. 2) Limited | Enhancer of zeste homolog 2 inhibitors |
| EP3102568B1 (en) | 2014-02-06 | 2018-06-27 | Heptares Therapeutics Limited | Bicyclic aza compounds as muscarinic m1 receptor agonists. |
| CN107148419A (zh) * | 2014-10-28 | 2017-09-08 | 葛兰素史密斯克莱知识产权（第2 号）有限公司 | Zeste增强子同源物2抑制剂 |
| TW201636344A (zh) | 2014-12-05 | 2016-10-16 | 美國禮來大藥廠 | Ｅｚｈ２抑制劑 |
| UY36758A (es) * | 2015-06-30 | 2016-12-30 | Glaxosmithkline Ip No 2 Ltd | Inhibidores del potenciador del homólogo zeste 2 |
| CN108025191A (zh) | 2015-08-24 | 2018-05-11 | Epizyme股份有限公司 | 治疗癌症的方法 |
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| DOP2015000270A (es) | 2016-02-15 |
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| KR20160003115A (ko) | 2016-01-08 |
| US9790212B2 (en) | 2017-10-17 |
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