KR20160003115A - 제스트 인핸서 상동체 2 억제제 - Google Patents
제스트 인핸서 상동체 2 억제제 Download PDFInfo
- Publication number
- KR20160003115A KR20160003115A KR1020157033651A KR20157033651A KR20160003115A KR 20160003115 A KR20160003115 A KR 20160003115A KR 1020157033651 A KR1020157033651 A KR 1020157033651A KR 20157033651 A KR20157033651 A KR 20157033651A KR 20160003115 A KR20160003115 A KR 20160003115A
- Authority
- KR
- South Korea
- Prior art keywords
- alkyl
- methyl
- carboxamide
- cycloalkyl
- heterocycloalkyl
- 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.)
- Ceased
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- 239000003112 inhibitor Substances 0.000 title abstract description 26
- 102000058017 Enhancer of Zeste Homolog 2 Human genes 0.000 title 1
- 101710196274 Histone-lysine N-methyltransferase EZH2 Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 191
- 238000000034 method Methods 0.000 claims abstract description 55
- 238000011282 treatment Methods 0.000 claims abstract description 54
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 48
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 26
- 201000011510 cancer Diseases 0.000 claims abstract description 25
- 102100038970 Histone-lysine N-methyltransferase EZH2 Human genes 0.000 claims abstract description 22
- 101000882127 Homo sapiens Histone-lysine N-methyltransferase EZH2 Proteins 0.000 claims abstract description 22
- -1 -B (OH) 2 Chemical group 0.000 claims description 357
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 228
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 130
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 102
- 125000001072 heteroaryl group Chemical group 0.000 claims description 98
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 98
- 239000001257 hydrogen Substances 0.000 claims description 84
- 229910052739 hydrogen Inorganic materials 0.000 claims description 84
- 229910052757 nitrogen Inorganic materials 0.000 claims description 81
- 125000003118 aryl group Chemical group 0.000 claims description 79
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 74
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 73
- 229910052736 halogen Inorganic materials 0.000 claims description 73
- 150000002367 halogens Chemical class 0.000 claims description 72
- 150000003839 salts Chemical class 0.000 claims description 72
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 68
- 229910052760 oxygen Inorganic materials 0.000 claims description 62
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 59
- 125000000217 alkyl group Chemical group 0.000 claims description 58
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 53
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 50
- 229910052717 sulfur Inorganic materials 0.000 claims description 48
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 44
- DAUYIKBTMNZABP-UHFFFAOYSA-N thiophene-3-carboxamide Chemical compound NC(=O)C=1C=CSC=1 DAUYIKBTMNZABP-UHFFFAOYSA-N 0.000 claims description 39
- 125000001424 substituent group Chemical group 0.000 claims description 36
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 28
- 229920006395 saturated elastomer Polymers 0.000 claims description 28
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 23
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 23
- 239000000460 chlorine Substances 0.000 claims description 23
- 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 23
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 22
- 239000001301 oxygen Substances 0.000 claims description 22
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 22
- 150000001602 bicycloalkyls Chemical group 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 125000005842 heteroatom Chemical group 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- DNUTZBZXLPWRJG-UHFFFAOYSA-M piperidine-1-carboxylate Chemical compound [O-]C(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-M 0.000 claims description 19
- 125000004043 oxo group Chemical group O=* 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 16
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 15
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 15
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 229910052801 chlorine Inorganic materials 0.000 claims description 15
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 15
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 15
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 14
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 claims description 14
- 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 claims description 14
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 14
- 125000003386 piperidinyl group Chemical group 0.000 claims description 13
- 206010025323 Lymphomas Diseases 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 12
- OZILNWNVMNXBDY-UHFFFAOYSA-N 1,4,6-trimethylpyridin-2-one Chemical compound CC=1C=C(C)N(C)C(=O)C=1 OZILNWNVMNXBDY-UHFFFAOYSA-N 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 11
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 10
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 230000001404 mediated effect Effects 0.000 claims description 9
- 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 claims description 9
- 239000011593 sulfur Chemical group 0.000 claims description 9
- 208000026310 Breast neoplasm Diseases 0.000 claims description 8
- 206010039491 Sarcoma Diseases 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 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
- 125000005843 halogen group Chemical group 0.000 claims description 7
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000002757 morpholinyl group Chemical group 0.000 claims description 7
- 125000004193 piperazinyl group Chemical group 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 206010006187 Breast cancer Diseases 0.000 claims description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 125000006582 (C5-C6) heterocycloalkyl group Chemical class 0.000 claims description 5
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
- 208000032839 leukemia Diseases 0.000 claims description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 210000002307 prostate Anatomy 0.000 claims description 5
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 5
- 125000001425 triazolyl group Chemical group 0.000 claims description 5
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 4
- FSPIBFKGESGOLU-UHFFFAOYSA-N 4,6-dimethyl-1h-pyridin-2-one Chemical compound CC1=CC(C)=NC(O)=C1 FSPIBFKGESGOLU-UHFFFAOYSA-N 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 4
- 125000002393 azetidinyl group Chemical group 0.000 claims description 4
- 208000005017 glioblastoma Diseases 0.000 claims description 4
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 4
- 210000004072 lung Anatomy 0.000 claims description 4
- 201000008968 osteosarcoma Diseases 0.000 claims description 4
- 125000002971 oxazolyl group Chemical group 0.000 claims description 4
- NYCVCXMSZNOGDH-UHFFFAOYSA-N pyrrolidine-1-carboxylic acid Chemical compound OC(=O)N1CCCC1 NYCVCXMSZNOGDH-UHFFFAOYSA-N 0.000 claims description 4
- NWRBBXWTEZRCQS-UHFFFAOYSA-N 6-methyl-4-propyl-1h-pyridin-2-one Chemical compound CCCC=1C=C(C)NC(=O)C=1 NWRBBXWTEZRCQS-UHFFFAOYSA-N 0.000 claims description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 210000004185 liver Anatomy 0.000 claims description 3
- 201000001441 melanoma Diseases 0.000 claims description 3
- ZZWWTDIYKHELAP-UHFFFAOYSA-N n-[(4,6-dimethyl-2-oxo-1h-pyridin-3-yl)methyl]-3-methyl-4-propan-2-yloxythiophene-2-carboxamide Chemical compound CC(C)OC1=CSC(C(=O)NCC=2C(NC(C)=CC=2C)=O)=C1C ZZWWTDIYKHELAP-UHFFFAOYSA-N 0.000 claims description 3
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 3
- 125000003566 oxetanyl group Chemical group 0.000 claims description 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
- 125000006570 (C5-C6) heteroaryl group Chemical class 0.000 claims description 2
- BMGPRFQPACSOQX-UHFFFAOYSA-N 4-methylthiophene-3-carboxamide Chemical compound CC1=CSC=C1C(N)=O BMGPRFQPACSOQX-UHFFFAOYSA-N 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- YAGFHTRELDRSAA-UHFFFAOYSA-N CC=1C(=CSC1)C(=O)N.CC1=CC(NC(=C1)C)=O Chemical compound CC=1C(=CSC1)C(=O)N.CC1=CC(NC(=C1)C)=O YAGFHTRELDRSAA-UHFFFAOYSA-N 0.000 claims description 2
- 208000007569 Giant Cell Tumors Diseases 0.000 claims description 2
- 208000032612 Glial tumor Diseases 0.000 claims description 2
- 206010018338 Glioma Diseases 0.000 claims description 2
- 208000033781 Thyroid carcinoma Diseases 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims description 2
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- 230000002611 ovarian Effects 0.000 claims description 2
- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 208000013077 thyroid gland carcinoma Diseases 0.000 claims description 2
- 208000005726 Inflammatory Breast Neoplasms Diseases 0.000 claims 1
- 206010021980 Inflammatory carcinoma of the breast Diseases 0.000 claims 1
- 201000004653 inflammatory breast carcinoma Diseases 0.000 claims 1
- 208000011580 syndromic disease Diseases 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 25
- 238000002560 therapeutic procedure Methods 0.000 abstract description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 189
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 169
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 145
- 239000000203 mixture Substances 0.000 description 134
- 238000006243 chemical reaction Methods 0.000 description 117
- 239000000243 solution Substances 0.000 description 114
- 239000007787 solid Substances 0.000 description 89
- 235000019439 ethyl acetate Nutrition 0.000 description 85
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 75
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 74
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 73
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 62
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 51
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
- 239000011734 sodium Substances 0.000 description 43
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- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 17
- 230000015572 biosynthetic process Effects 0.000 description 17
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Classifications
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- 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
- C07D409/14—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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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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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
-
- 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
-
- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Epidemiology (AREA)
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20160003115A true KR20160003115A (ko) | 2016-01-08 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020157033651A Ceased KR20160003115A (ko) | 2013-04-30 | 2014-04-25 | 제스트 인핸서 상동체 2 억제제 |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US9505745B2 (enExample) |
| EP (1) | EP2991980B1 (enExample) |
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Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2812001B1 (en) * | 2012-02-10 | 2017-06-14 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| BR112015008447A2 (pt) | 2012-10-15 | 2017-07-04 | Epizyme Inc | métodos para tratar câncer |
| CA2910873A1 (en) * | 2013-04-30 | 2014-11-06 | Glaxosmithkline Intellectual Property (No.2) Limited | Enhancer of zeste homolog 2 inhibitors |
| JP2016523955A (ja) | 2013-07-10 | 2016-08-12 | グラクソスミスクライン、インテレクチュアル、プロパティー、ナンバー２、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｎｏ．２ Ｌｉｍｉｔｅｄ | Ｚｅｓｔｅホモログ２エンハンサー阻害剤 |
| HRP20241145T1 (hr) | 2014-02-06 | 2024-11-22 | Nxera Pharma Uk Limited | Biciklički aza spojevi kao agonisti muskarinskih receptora |
| KR20170068603A (ko) * | 2014-10-28 | 2017-06-19 | 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 | 제스트 인핸서 상동체 2 억제제 |
| 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 |
| US10493076B2 (en) | 2015-08-24 | 2019-12-03 | Epizyme, Inc. | Method for treating cancer |
| TW201718598A (zh) * | 2015-08-27 | 2017-06-01 | 美國禮來大藥廠 | Ｅｚｈ２抑制劑 |
| EP3370725A4 (en) * | 2015-11-06 | 2019-07-03 | Epizyme, Inc. | PEDIATRIC DOSAGE FOR THE TREATMENT OF CANCER WITH AN EZH2 INHIBITOR |
| HRP20192209T1 (hr) | 2015-11-19 | 2020-07-24 | Jiangsu Hengrui Medicine Co., Ltd. | Derivati benzofurana, postupci njihove pripreme i njihova uporaba u medicini |
| WO2017191545A1 (en) | 2016-05-05 | 2017-11-09 | Glaxosmithkline Intellectual Property (No.2) Limited | Enhancer of zeste homolog 2 inhibitors |
| US20170337814A1 (en) * | 2016-05-20 | 2017-11-23 | Donald Edward Morgan | Safety alerting drivers device and system |
| KR102351782B1 (ko) | 2016-09-07 | 2022-01-17 | 상하이 하이헤 파마수티컬 컴퍼니 리미티드 | 피리도 5원 방향족 고리계 화합물, 이의 제조 방법 및 용도 |
| WO2018125983A1 (en) | 2016-12-30 | 2018-07-05 | Mitobridge, Inc. | Oxopyridine derivatives useful as aminocarboxymuconate semialdehyde decarboxylase (acmsd) inhibitors |
| US10266542B2 (en) | 2017-03-15 | 2019-04-23 | Mirati Therapeutics, Inc. | EZH2 inhibitors |
| FI4043466T3 (fi) | 2018-01-31 | 2024-10-30 | Mirati Therapeutics Inc | Prc2:n estäjiä |
| CA3104209A1 (en) | 2018-07-09 | 2020-01-16 | Fondation Asile Des Aveugles | Inhibition of prc2 subunits to treat eye disorders |
| JP7624404B2 (ja) | 2019-04-22 | 2025-01-30 | ミラティ セラピューティクス，インク． | Ｐｒｃ２阻害剤としてのナフチリジン誘導体 |
| BR112021024131A2 (pt) * | 2019-05-31 | 2022-01-11 | Haisco Pharmaceuticals Pte Ltd | Derivado de anel inibidor de btk, método de preparação para o mesmo e aplicação farmacêutica do mesmo |
| WO2020247475A1 (en) | 2019-06-05 | 2020-12-10 | Mirati Therapeutics, Inc. | Imidazo[1,2-c]pyrimidine derivatives as prc2 inhibitors for treating cancer |
| JP2022545467A (ja) | 2019-08-22 | 2022-10-27 | ジュノー セラピューティクス インコーポレイテッド | Ｔ細胞療法とｚｅｓｔｅホモログ２エンハンサー（ＥＺＨ２）阻害剤との併用療法および関連方法 |
| CN110964200A (zh) * | 2019-12-19 | 2020-04-07 | 新纳奇材料科技江苏有限公司 | 一种基于聚硅氧烷馏出物的羟基封端聚硅氧烷的制备方法 |
| CN114787143A (zh) * | 2019-12-23 | 2022-07-22 | 四川海思科制药有限公司 | Zeste增强子同源物2抑制剂及其用途 |
| CN111233768B (zh) * | 2020-03-18 | 2021-08-03 | 徐州圣元化工有限公司 | 一种3-(二氟甲基)-1-甲基-1h-吡唑-4-羧酸乙酯的制备方法 |
| WO2023230205A1 (en) | 2022-05-25 | 2023-11-30 | Ikena Oncology, Inc. | Mek inhibitors and uses thereof |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2007519753A (ja) * | 2004-01-30 | 2007-07-19 | スミスクライン ビーチャム コーポレーション | 化合物 |
| CN1989131A (zh) * | 2004-03-30 | 2007-06-27 | 希龙公司 | 取代的噻吩衍生物用作抗癌药 |
| US7696352B2 (en) * | 2004-06-18 | 2010-04-13 | Millennium Pharmaceuticals, Inc. | Factor Xa inhibitors |
| US8163749B2 (en) | 2005-12-14 | 2012-04-24 | Bristol-Myers Squibb Company | Six-membered heterocycles useful as serine protease inhibitors |
| SG178273A1 (en) * | 2009-08-07 | 2012-03-29 | Merck Patent Gmbh | Novel azaheterocyclic compounds |
| ES2528269T3 (es) | 2010-05-07 | 2015-02-06 | Glaxosmithkline Llc | Azaindazoles |
| HRP20170736T1 (hr) | 2010-05-07 | 2017-07-28 | Glaxosmithkline Llc | Indoli |
| ES2534804T3 (es) | 2010-05-07 | 2015-04-28 | Glaxosmithkline Llc | Indazoles |
| EP2646020B1 (en) | 2010-12-01 | 2016-09-21 | Glaxosmithkline LLC | Indoles |
| EP3323820B1 (en) | 2011-02-28 | 2023-05-10 | Epizyme, Inc. | Substituted 6,5-fused bicyclic heteroaryl compounds |
| TW201733984A (zh) * | 2011-04-13 | 2017-10-01 | 雅酶股份有限公司 | 經取代之苯化合物 |
| JO3438B1 (ar) | 2011-04-13 | 2019-10-20 | Epizyme Inc | مركبات بنزين مستبدلة بأريل أو أريل غير متجانس |
| CN103987842A (zh) * | 2011-09-30 | 2014-08-13 | 葛兰素史密斯克莱有限责任公司 | 治疗癌症的方法 |
| EP2812001B1 (en) | 2012-02-10 | 2017-06-14 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| PL3184523T3 (pl) | 2012-04-13 | 2019-12-31 | Epizyme Inc | Bromowodorek N-((4,6-dimetylo-2-okso-1,2-dihydropirydyn-3-ylo)metylo)-5- (etylo(tetrahydro-2H-piran-4-ylo)amino)-4-metylo-4'-(morfolinometylo)-[1,1'- bifenylo]-3-karboksyamidu do zastosowania w leczeniu zaburzenia proliferacji komórkowej układu hematologicznego |
| WO2013173441A2 (en) | 2012-05-16 | 2013-11-21 | Glaxosmithkline Llc | Enhancer of zeste homolog 2 inhibitors |
| CA2910873A1 (en) * | 2013-04-30 | 2014-11-06 | Glaxosmithkline Intellectual Property (No.2) Limited | Enhancer of zeste homolog 2 inhibitors |
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2014
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- 2014-04-25 PE PE2015002298A patent/PE20151981A1/es not_active Application Discontinuation
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- 2014-04-25 WO PCT/IB2014/061012 patent/WO2014177982A1/en not_active Ceased
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2015
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- 2015-10-30 DO DO2015000270A patent/DOP2015000270A/es unknown
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2016
- 2016-10-13 US US15/292,200 patent/US9790212B2/en not_active Expired - Fee Related
Also Published As
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|---|---|
| MX2015015144A (es) | 2016-02-18 |
| JP6373973B2 (ja) | 2018-08-15 |
| WO2014177982A1 (en) | 2014-11-06 |
| US20160102083A1 (en) | 2016-04-14 |
| CN105308038B (zh) | 2018-05-29 |
| EP2991980B1 (en) | 2019-01-02 |
| EA030196B1 (ru) | 2018-07-31 |
| ZA201507398B (en) | 2017-01-25 |
| PH12015502414A1 (en) | 2016-02-22 |
| CN105308038A (zh) | 2016-02-03 |
| DOP2015000270A (es) | 2016-02-15 |
| AU2014261075B2 (en) | 2017-01-19 |
| SG11201508203TA (en) | 2015-11-27 |
| BR112015027527A2 (pt) | 2017-07-25 |
| JP2016517878A (ja) | 2016-06-20 |
| ES2717680T3 (es) | 2019-06-24 |
| CL2015003200A1 (es) | 2016-04-22 |
| EA201592068A1 (ru) | 2016-05-31 |
| CA2910873A1 (en) | 2014-11-06 |
| HK1214815A1 (zh) | 2016-08-05 |
| US9790212B2 (en) | 2017-10-17 |
| PE20151981A1 (es) | 2016-01-14 |
| AU2014261075A1 (en) | 2015-11-05 |
| NZ630205A (en) | 2017-03-31 |
| EP2991980A1 (en) | 2016-03-09 |
| US9505745B2 (en) | 2016-11-29 |
| US20170029412A1 (en) | 2017-02-02 |
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