ES2717680T3 - Potenciador de inhibidores del homólogo de Zeste 2 - Google Patents
Potenciador de inhibidores del homólogo de Zeste 2 Download PDFInfo
- Publication number
- ES2717680T3 ES2717680T3 ES14727619T ES14727619T ES2717680T3 ES 2717680 T3 ES2717680 T3 ES 2717680T3 ES 14727619 T ES14727619 T ES 14727619T ES 14727619 T ES14727619 T ES 14727619T ES 2717680 T3 ES2717680 T3 ES 2717680T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- alkyl
- oxo
- carboxamide
- dimethyl
- 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.)
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- 239000003112 inhibitor Substances 0.000 title description 31
- QTTMOCOWZLSYSV-QWAPEVOJSA-M equilin sodium sulfate Chemical compound [Na+].[O-]S(=O)(=O)OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4C3=CCC2=C1 QTTMOCOWZLSYSV-QWAPEVOJSA-M 0.000 title description 3
- -1 2-hydroxyl Chemical group 0.000 claims description 399
- 150000001875 compounds Chemical class 0.000 claims description 215
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 148
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 142
- 239000001257 hydrogen Substances 0.000 claims description 66
- 229910052739 hydrogen Inorganic materials 0.000 claims description 66
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 65
- 229910003827 NRaRb Inorganic materials 0.000 claims description 63
- 150000003839 salts Chemical class 0.000 claims description 62
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 60
- 125000001072 heteroaryl group Chemical group 0.000 claims description 54
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 52
- 238000011282 treatment Methods 0.000 claims description 52
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 50
- 229910052736 halogen Inorganic materials 0.000 claims description 49
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 48
- 150000002367 halogens Chemical class 0.000 claims description 48
- 229910052760 oxygen Inorganic materials 0.000 claims description 47
- DAUYIKBTMNZABP-UHFFFAOYSA-N thiophene-3-carboxamide Chemical compound NC(=O)C=1C=CSC=1 DAUYIKBTMNZABP-UHFFFAOYSA-N 0.000 claims description 47
- 206010028980 Neoplasm Diseases 0.000 claims description 44
- 229910052717 sulfur Inorganic materials 0.000 claims description 43
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 41
- 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 39
- 125000003118 aryl group Chemical group 0.000 claims description 35
- 229910052757 nitrogen Inorganic materials 0.000 claims description 33
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 239000008194 pharmaceutical composition Substances 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- 201000011510 cancer Diseases 0.000 claims description 24
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 23
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
- 150000001412 amines Chemical class 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 20
- 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 18
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 17
- 239000001301 oxygen Substances 0.000 claims description 17
- 101100456896 Drosophila melanogaster metl gene Proteins 0.000 claims description 16
- 125000004429 atom Chemical group 0.000 claims description 16
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 16
- 229920006395 saturated elastomer Polymers 0.000 claims description 16
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
- 239000005977 Ethylene Substances 0.000 claims description 15
- 125000003386 piperidinyl group Chemical group 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 14
- 125000004043 oxo group Chemical group O=* 0.000 claims description 14
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 14
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 239000011593 sulfur Chemical group 0.000 claims description 12
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 11
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 9
- 125000002883 imidazolyl group Chemical group 0.000 claims description 9
- 125000002757 morpholinyl group Chemical group 0.000 claims description 9
- 125000004193 piperazinyl group Chemical group 0.000 claims description 9
- 125000006564 (C4-C8) cycloalkyl group Chemical group 0.000 claims description 8
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 125000002971 oxazolyl group Chemical group 0.000 claims description 8
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 8
- 238000002560 therapeutic procedure Methods 0.000 claims description 8
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 125000001425 triazolyl group Chemical group 0.000 claims description 8
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 7
- 125000004306 triazinyl group Chemical group 0.000 claims description 7
- 229910052727 yttrium Inorganic materials 0.000 claims description 7
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 6
- 125000001400 nonyl 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])C([H])([H])[H] 0.000 claims description 6
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 5
- 125000002393 azetidinyl group Chemical group 0.000 claims description 5
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 claims description 5
- 125000005043 dihydropyranyl group Chemical group O1C(CCC=C1)* 0.000 claims description 5
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 5
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 claims description 4
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 claims description 4
- ILWJAOPQHOZXAN-UHFFFAOYSA-N 1,3-dithianyl Chemical group [CH]1SCCCS1 ILWJAOPQHOZXAN-UHFFFAOYSA-N 0.000 claims description 4
- KFHQOZXAFUKFNB-UHFFFAOYSA-N 1,3-oxathiolanyl Chemical group [CH]1OCCS1 KFHQOZXAFUKFNB-UHFFFAOYSA-N 0.000 claims description 4
- 125000005940 1,4-dioxanyl group Chemical group 0.000 claims description 4
- HKDFRDIIELOLTJ-UHFFFAOYSA-N 1,4-dithianyl Chemical group [CH]1CSCCS1 HKDFRDIIELOLTJ-UHFFFAOYSA-N 0.000 claims description 4
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 4
- 125000002636 imidazolinyl group Chemical group 0.000 claims description 4
- 125000005968 oxazolinyl group Chemical group 0.000 claims description 4
- 125000003072 pyrazolidinyl group Chemical group 0.000 claims description 4
- 125000002755 pyrazolinyl group Chemical group 0.000 claims description 4
- 229910052705 radium Inorganic materials 0.000 claims description 4
- 229910052701 rubidium Inorganic materials 0.000 claims description 4
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 4
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 3
- 125000004502 1,2,3-oxadiazolyl group Chemical group 0.000 claims description 3
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 3
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 3
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 claims description 3
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 claims description 3
- 125000004069 aziridinyl group Chemical group 0.000 claims description 3
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000004652 decahydroisoquinolinyl group Chemical group C1(NCCC2CCCCC12)* 0.000 claims description 3
- 125000004856 decahydroquinolinyl group Chemical group N1(CCCC2CCCCC12)* 0.000 claims description 3
- 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([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 3
- 125000005433 dihydrobenzodioxinyl group Chemical group O1C(COC2=C1C=CC=C2)* 0.000 claims description 3
- 125000005435 dihydrobenzoxazolyl group Chemical group O1C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
- 125000005984 hexahydro-1H-1,4-diazepinyl group Chemical group 0.000 claims description 3
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 3
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 3
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 3
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 3
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000004930 octahydroisoquinolinyl group Chemical group C1(NCCC2CCCC=C12)* 0.000 claims description 3
- 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 3
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 claims description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 3
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 3
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 3
- 125000005065 undecenyl group Chemical group C(=CCCCCCCCCC)* 0.000 claims description 3
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 101100322888 Escherichia coli (strain K12) metL gene Proteins 0.000 claims description 2
- 101100521345 Mus musculus Prop1 gene Proteins 0.000 claims description 2
- 108700017836 Prophet of Pit-1 Proteins 0.000 claims description 2
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
- 125000001188 haloalkyl group Chemical group 0.000 claims description 2
- XBXCNNQPRYLIDE-UHFFFAOYSA-M n-tert-butylcarbamate Chemical compound CC(C)(C)NC([O-])=O XBXCNNQPRYLIDE-UHFFFAOYSA-M 0.000 claims description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 2
- 241000009298 Trigla lyra Species 0.000 claims 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 261
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 178
- 239000000203 mixture Substances 0.000 description 140
- 238000006243 chemical reaction Methods 0.000 description 129
- 239000000243 solution Substances 0.000 description 108
- 239000007787 solid Substances 0.000 description 101
- 235000019439 ethyl acetate Nutrition 0.000 description 89
- 238000005481 NMR spectroscopy Methods 0.000 description 86
- YMWUJEATGCHHMB-UHFFFAOYSA-N dichloromethane Natural products ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 86
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 80
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 80
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 78
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 70
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 58
- 235000002639 sodium chloride Nutrition 0.000 description 55
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 54
- 239000000741 silica gel Substances 0.000 description 48
- 229910002027 silica gel Inorganic materials 0.000 description 48
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 45
- 238000000034 method Methods 0.000 description 44
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 39
- 239000011734 sodium Substances 0.000 description 39
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 35
- 230000000694 effects Effects 0.000 description 35
- 239000012267 brine Substances 0.000 description 34
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 34
- 238000004587 chromatography analysis Methods 0.000 description 33
- 239000003795 chemical substances by application Substances 0.000 description 31
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- FPIRBHDGWMWJEP-UHFFFAOYSA-N 1-hydroxy-7-azabenzotriazole Chemical compound C1=CN=C2N(O)N=NC2=C1 FPIRBHDGWMWJEP-UHFFFAOYSA-N 0.000 description 19
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- 238000003786 synthesis reaction Methods 0.000 description 14
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- FCKSGPKSSPUXOP-UHFFFAOYSA-N methyl 4-methylthiophene-3-carboxylate Chemical compound COC(=O)C1=CSC=C1C FCKSGPKSSPUXOP-UHFFFAOYSA-N 0.000 description 12
- 238000004007 reversed phase HPLC Methods 0.000 description 12
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 12
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
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- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 10
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Classifications
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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
- C07D409/14—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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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
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- 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
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- 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)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Epidemiology (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361817436P | 2013-04-30 | 2013-04-30 | |
| US201361842038P | 2013-07-02 | 2013-07-02 | |
| US201361907024P | 2013-11-21 | 2013-11-21 | |
| US201461936460P | 2014-02-06 | 2014-02-06 | |
| PCT/IB2014/061012 WO2014177982A1 (en) | 2013-04-30 | 2014-04-25 | Enhancer of zeste homolog 2 inhibitors |
Publications (1)
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| ES2717680T3 true ES2717680T3 (es) | 2019-06-24 |
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| ES14727619T Active ES2717680T3 (es) | 2013-04-30 | 2014-04-25 | Potenciador de inhibidores del homólogo de Zeste 2 |
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|---|---|
| US (2) | US9505745B2 (OSRAM) |
| EP (1) | EP2991980B1 (OSRAM) |
| JP (1) | JP6373973B2 (OSRAM) |
| KR (1) | KR20160003115A (OSRAM) |
| CN (1) | CN105308038B (OSRAM) |
| AU (1) | AU2014261075B2 (OSRAM) |
| BR (1) | BR112015027527A2 (OSRAM) |
| CA (1) | CA2910873A1 (OSRAM) |
| CL (1) | CL2015003200A1 (OSRAM) |
| DO (1) | DOP2015000270A (OSRAM) |
| EA (1) | EA030196B1 (OSRAM) |
| ES (1) | ES2717680T3 (OSRAM) |
| HK (1) | HK1214815A1 (OSRAM) |
| MX (1) | MX2015015144A (OSRAM) |
| NZ (1) | NZ630205A (OSRAM) |
| PE (1) | PE20151981A1 (OSRAM) |
| PH (1) | PH12015502414A1 (OSRAM) |
| SG (1) | SG11201508203TA (OSRAM) |
| WO (1) | WO2014177982A1 (OSRAM) |
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| EP2812001B1 (en) * | 2012-02-10 | 2017-06-14 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| NZ706836A (en) | 2012-10-15 | 2019-02-22 | Epizyme Inc | Methods of treating cancer |
| KR20160003115A (ko) * | 2013-04-30 | 2016-01-08 | 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 | 제스트 인핸서 상동체 2 억제제 |
| ES2640386T3 (es) | 2013-07-10 | 2017-11-02 | Glaxosmithkline Intellectual Property (No. 2) Limited | Potenciador de inhibidores del homólogo Zeste 2 |
| SMT202400446T1 (it) | 2014-02-06 | 2024-11-15 | Nxera Pharma Uk Ltd | Composti aza biciclici come agonisti del recettore muscarinico |
| 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 |
| AR102767A1 (es) * | 2014-12-05 | 2017-03-22 | Lilly Co Eli | Inhibidores de ezh2 |
| 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 |
| ES2760510T3 (es) | 2015-11-19 | 2020-05-14 | Jiangsu Hengrui Medicine Co | Derivado de benzofurano, método de preparación del mismo y uso del mismo en medicina |
| MX2018013519A (es) * | 2016-05-05 | 2019-03-14 | Glaxosmithkline Ip No 2 Ltd | Inhibidores del potenciador del homologo zeste 2. |
| US20170337814A1 (en) * | 2016-05-20 | 2017-11-23 | Donald Edward Morgan | Safety alerting drivers device and system |
| MX390117B (es) | 2016-09-07 | 2025-03-20 | Haihe Biopharma Co Ltd | Compuesto de anillo aromatico de pirido de cinco elementos, metodo de preparacion y uso del mismo. |
| US20190367457A1 (en) | 2016-12-30 | 2019-12-05 | Mitobridge, Inc. | Oxopyridine derivatives useful as aminocarboxymuconate semialdehyde decarboxylase (acmsd) inhibitors |
| US10266542B2 (en) | 2017-03-15 | 2019-04-23 | Mirati Therapeutics, Inc. | EZH2 inhibitors |
| HUE059536T2 (hu) | 2018-01-31 | 2022-11-28 | Mirati Therapeutics Inc | PRC2-inhibitorok |
| CN112399857A (zh) | 2018-07-09 | 2021-02-23 | 盲人庇护基金会 | Prc2亚单位的抑制治疗眼失调 |
| EP3959214A1 (en) | 2019-04-22 | 2022-03-02 | Mirati Therapeutics, Inc. | Naphthyridine derivatives as prc2 inhibitors |
| 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 |
| CN114269748A (zh) | 2019-06-05 | 2022-04-01 | 米拉蒂医疗股份有限公司 | 作为用于治疗癌症的PRC2抑制剂的咪唑并[1,2-c]嘧啶衍生物 |
| CN114555112A (zh) | 2019-08-22 | 2022-05-27 | 朱诺治疗学股份有限公司 | T细胞疗法和zeste增强子同源物2(ezh2)抑制剂的组合疗法及相关方法 |
| 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 |
| CN119768393A (zh) | 2022-05-25 | 2025-04-04 | 医肯纳肿瘤学公司 | Mek抑制剂和其用途 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1708697A4 (en) * | 2004-01-30 | 2007-11-28 | Smithkline Beecham Corp | CHEMICAL COMPOUNDS |
| EP1732919A1 (en) * | 2004-03-30 | 2006-12-20 | Chiron Corporation | Substituted thiophene derivatives as anti-cancer agents |
| US7696352B2 (en) * | 2004-06-18 | 2010-04-13 | Millennium Pharmaceuticals, Inc. | Factor Xa inhibitors |
| WO2007070818A1 (en) | 2005-12-14 | 2007-06-21 | 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 |
| ES2534804T3 (es) * | 2010-05-07 | 2015-04-28 | Glaxosmithkline Llc | Indazoles |
| ES2528269T3 (es) * | 2010-05-07 | 2015-02-06 | Glaxosmithkline Llc | Azaindazoles |
| CN102970869B (zh) | 2010-05-07 | 2014-07-16 | 葛兰素史密斯克莱有限责任公司 | 吲哚 |
| US8765792B2 (en) | 2010-12-01 | 2014-07-01 | Glaxosmithkline Llc | Indoles |
| EP2681216B1 (en) | 2011-02-28 | 2017-09-27 | Epizyme, Inc. | Substituted 6,5-fused bicyclic heteroaryl compounds |
| TWI598336B (zh) | 2011-04-13 | 2017-09-11 | 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 |
| US9730925B2 (en) * | 2011-09-30 | 2017-08-15 | Glaxomithkline Llc | Methods of treating cancer |
| EP2812001B1 (en) | 2012-02-10 | 2017-06-14 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| RU2658911C2 (ru) | 2012-04-13 | 2018-06-26 | Эпизайм, Инк. | Солевая форма ингибитора гистон-метилтрансферазы ezh2 человека |
| US9562041B2 (en) | 2012-05-16 | 2017-02-07 | Glaxosmithkline Llc | Enhancer of zeste homolog 2 inhibitors |
| KR20160003115A (ko) * | 2013-04-30 | 2016-01-08 | 글락소스미스클라인 인털렉츄얼 프로퍼티 (넘버 2) 리미티드 | 제스트 인핸서 상동체 2 억제제 |
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| AU2014261075B2 (en) | 2017-01-19 |
| BR112015027527A2 (pt) | 2017-07-25 |
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