CA2910873A1 - Enhancer of zeste homolog 2 inhibitors - Google Patents

Info

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

2013-04-30

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

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 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
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• VKIJWCDJJOLWKH-UHFFFAOYSA-N ethyl n-[4-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methylcarbamoyl]-3-methylthiophen-2-yl]-n-ethylcarbamate Chemical compound CC1=C(N(CC)C(=O)OCC)SC=C1C(=O)NCC1=C(C)C=C(C)NC1=O VKIJWCDJJOLWKH-UHFFFAOYSA-N 0.000 claims 1
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