RU2695227C9 - Производные 1,3,4-оксадиазолсульфамида в качестве ингибитора гистондеацетилазы 6 и содержащая их фармацевтическая композиция - Google Patents
Производные 1,3,4-оксадиазолсульфамида в качестве ингибитора гистондеацетилазы 6 и содержащая их фармацевтическая композиция Download PDFInfo
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- RU2695227C9 RU2695227C9 RU2018106904A RU2018106904A RU2695227C9 RU 2695227 C9 RU2695227 C9 RU 2695227C9 RU 2018106904 A RU2018106904 A RU 2018106904A RU 2018106904 A RU2018106904 A RU 2018106904A RU 2695227 C9 RU2695227 C9 RU 2695227C9
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- Prior art keywords
- mmol
- methyl
- sulfonamide
- alkyl
- stirred
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
- UYJSDFHXPYMBBN-UHFFFAOYSA-N 1,3,4-oxadiazole sulfamide Chemical class NS(N)(=O)=O.c1nnco1 UYJSDFHXPYMBBN-UHFFFAOYSA-N 0.000 title claims description 19
- 229940122617 Histone deacetylase 6 inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 238
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 201000010099 disease Diseases 0.000 claims abstract description 37
- 238000000034 method Methods 0.000 claims abstract description 22
- 102000003964 Histone deacetylase Human genes 0.000 claims abstract description 21
- 108090000353 Histone deacetylase Proteins 0.000 claims abstract description 21
- 230000001404 mediated effect Effects 0.000 claims abstract description 5
- -1 substituted Chemical class 0.000 claims description 275
- 125000003118 aryl group Chemical group 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 8
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 238000011321 prophylaxis Methods 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 10
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 6
- 125000004076 pyridyl group Chemical group 0.000 claims 5
- 125000002947 alkylene group Chemical group 0.000 claims 4
- 150000003222 pyridines Chemical class 0.000 claims 3
- 125000003566 oxetanyl group Chemical group 0.000 claims 2
- 230000000694 effects Effects 0.000 abstract description 23
- 230000002401 inhibitory effect Effects 0.000 abstract description 10
- 239000000126 substance Substances 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 717
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 677
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 495
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 346
- 239000011541 reaction mixture Substances 0.000 description 301
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 261
- 239000000243 solution Substances 0.000 description 246
- 229920006395 saturated elastomer Polymers 0.000 description 243
- 235000019439 ethyl acetate Nutrition 0.000 description 226
- 239000007787 solid Substances 0.000 description 196
- 238000000605 extraction Methods 0.000 description 191
- 239000012044 organic layer Substances 0.000 description 191
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 189
- 239000007864 aqueous solution Substances 0.000 description 167
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 166
- 229910004298 SiO 2 Inorganic materials 0.000 description 161
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 144
- 239000011780 sodium chloride Substances 0.000 description 131
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 130
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 123
- 238000006243 chemical reaction Methods 0.000 description 123
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 98
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 96
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 82
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 74
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 72
- 239000000203 mixture Substances 0.000 description 67
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 66
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 65
- 235000017557 sodium bicarbonate Nutrition 0.000 description 65
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
- 230000002829 reductive effect Effects 0.000 description 57
- 239000002904 solvent Substances 0.000 description 57
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 56
- 235000001968 nicotinic acid Nutrition 0.000 description 56
- 239000011664 nicotinic acid Substances 0.000 description 56
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 54
- 238000001914 filtration Methods 0.000 description 53
- 239000002244 precipitate Substances 0.000 description 53
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 49
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
- IYXUFOCLMOXQSL-UHFFFAOYSA-N (2,2-difluoroacetyl) 2,2-difluoroacetate Chemical compound FC(F)C(=O)OC(=O)C(F)F IYXUFOCLMOXQSL-UHFFFAOYSA-N 0.000 description 41
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 40
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 38
- 235000019270 ammonium chloride Nutrition 0.000 description 37
- 238000000746 purification Methods 0.000 description 37
- 239000012043 crude product Substances 0.000 description 32
- JXHYCCGOZUGBFD-UHFFFAOYSA-N benzoic acid;hydrochloride Chemical compound Cl.OC(=O)C1=CC=CC=C1 JXHYCCGOZUGBFD-UHFFFAOYSA-N 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
- 108010023925 Histone Deacetylase 6 Proteins 0.000 description 30
- 102100022537 Histone deacetylase 6 Human genes 0.000 description 30
- IBTWUVRCFHJPKN-UHFFFAOYSA-N hydron;pyridine-3-carboxylic acid;chloride Chemical compound Cl.OC(=O)C1=CC=CN=C1 IBTWUVRCFHJPKN-UHFFFAOYSA-N 0.000 description 29
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 24
- 239000000725 suspension Substances 0.000 description 24
- 239000007788 liquid Substances 0.000 description 23
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 21
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
- YSHOWEKUVWPFNR-UHFFFAOYSA-N burgess reagent Chemical compound CC[N+](CC)(CC)S(=O)(=O)N=C([O-])OC YSHOWEKUVWPFNR-UHFFFAOYSA-N 0.000 description 18
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 18
- 239000012141 concentrate Substances 0.000 description 17
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 14
- 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 description 14
- 235000011054 acetic acid Nutrition 0.000 description 13
- 239000012230 colorless oil Substances 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 description 12
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 12
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
- 239000012312 sodium hydride Substances 0.000 description 12
- RADPVVIPUAGLPO-PHIMTYICSA-N (3r,5s)-3,5-dimethyl-1-phenylpiperazine Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=CC=CC=C1 RADPVVIPUAGLPO-PHIMTYICSA-N 0.000 description 11
- 206010028980 Neoplasm Diseases 0.000 description 11
- 239000003921 oil Substances 0.000 description 11
- DWXLVZSMXXCSMJ-UHFFFAOYSA-N piperazine-1-sulfonamide Chemical compound NS(=O)(=O)N1CCNCC1 DWXLVZSMXXCSMJ-UHFFFAOYSA-N 0.000 description 11
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 10
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 10
- IRQSKJQDKUAART-UHFFFAOYSA-N methyl 6-(bromomethyl)pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=C(CBr)N=C1 IRQSKJQDKUAART-UHFFFAOYSA-N 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- GMMLZJCPYIMGON-UHFFFAOYSA-N N-[[2-fluoro-4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-phenylpiperazine-1-sulfonamide hydrochloride Chemical compound Cl.Fc1cc(ccc1CN(c1ccccc1)S(=O)(=O)N1CCNCC1)-c1nnc(o1)C(F)(F)F GMMLZJCPYIMGON-UHFFFAOYSA-N 0.000 description 9
- FKRNPUPIHAVTJL-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-N-phenylpiperazine-1-sulfonamide hydrochloride Chemical compound Cl.FC(F)c1nnc(o1)-c1ccc(CN(c2ccccc2)S(=O)(=O)N2CCNCC2)c(F)c1 FKRNPUPIHAVTJL-UHFFFAOYSA-N 0.000 description 9
- SZTLIGHKSIXTGE-UHFFFAOYSA-N O1CC(C1)N1CCN(CC1)C1=CC=CC=C1 Chemical compound O1CC(C1)N1CCN(CC1)C1=CC=CC=C1 SZTLIGHKSIXTGE-UHFFFAOYSA-N 0.000 description 9
- 201000011510 cancer Diseases 0.000 description 9
- 125000001072 heteroaryl group Chemical group 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- GRBUTWWFTFQSMF-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-methylpiperazine Chemical compound C1CNC(C)CN1C1=CC=CC(Cl)=C1 GRBUTWWFTFQSMF-UHFFFAOYSA-N 0.000 description 8
- CXKADMFVIMIQMK-UHFFFAOYSA-N 3-methyl-1-(3-methylphenyl)piperazine Chemical compound C1CNC(C)CN1C1=CC=CC(C)=C1 CXKADMFVIMIQMK-UHFFFAOYSA-N 0.000 description 8
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 8
- 229930040373 Paraformaldehyde Natural products 0.000 description 8
- 229920002866 paraformaldehyde Polymers 0.000 description 8
- NHJFHAQBMGFFPV-UHFFFAOYSA-N 1,1-dioxo-1,4-thiazinane-4-sulfonamide Chemical compound NS(=O)(=O)N1CCS(=O)(=O)CC1 NHJFHAQBMGFFPV-UHFFFAOYSA-N 0.000 description 7
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 7
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 7
- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 7
- 229940124530 sulfonamide Drugs 0.000 description 7
- 230000002194 synthesizing effect Effects 0.000 description 7
- KGXZZTJAKXHMFS-BETUJISGSA-N (2R,6S)-1-ethyl-2,6-dimethyl-4-phenylpiperazine Chemical compound C(C)N1[C@H](CN(C[C@H]1C)C1=CC=CC=C1)C KGXZZTJAKXHMFS-BETUJISGSA-N 0.000 description 6
- VCGNHCJYGWZGMH-UHFFFAOYSA-N 1,2-dimethyl-4-(3-methylphenyl)piperazine Chemical compound CC1CN(CCN1C)C=1C=C(C=CC=1)C VCGNHCJYGWZGMH-UHFFFAOYSA-N 0.000 description 6
- VTVVNBWAQWOSKB-UHFFFAOYSA-N 1-(3-chloro-4-fluorophenyl)-4-(oxetan-3-yl)piperazine Chemical compound ClC=1C=C(C=CC=1F)N1CCN(CC1)C1COC1 VTVVNBWAQWOSKB-UHFFFAOYSA-N 0.000 description 6
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- MALBGOTVCYKCHP-UHFFFAOYSA-N 1-(3-chloro-4-fluorophenyl)-4-propan-2-ylpiperazine Chemical compound ClC=1C=C(C=CC=1F)N1CCN(CC1)C(C)C MALBGOTVCYKCHP-UHFFFAOYSA-N 0.000 description 6
- XVJGMMIQHDGDBM-TXEJJXNPSA-N 1-[(2R,6S)-2,6-dimethyl-4-phenylpiperazin-1-yl]ethanone Chemical compound C(C)(=O)N1[C@H](CN(C[C@H]1C)C1=CC=CC=C1)C XVJGMMIQHDGDBM-TXEJJXNPSA-N 0.000 description 6
- ILNDDBQCSMETGT-UHFFFAOYSA-N 2-methyl-4-(3-methylphenyl)-1-(oxetan-3-yl)piperazine Chemical compound CC1CN(CCN1C1COC1)C=1C=C(C=CC=1)C ILNDDBQCSMETGT-UHFFFAOYSA-N 0.000 description 6
- PMMFKLZNHANHKY-UHFFFAOYSA-N 4-(3-chlorophenyl)-1,2-dimethylpiperazine Chemical compound ClC=1C=C(C=CC=1)N1CC(N(CC1)C)C PMMFKLZNHANHKY-UHFFFAOYSA-N 0.000 description 6
- ZEZGEMKPVIDDHY-UHFFFAOYSA-N 4-(3-chlorophenyl)-2-methyl-1-(oxetan-3-yl)piperazine Chemical compound ClC=1C=C(C=CC=1)N1CC(N(CC1)C1COC1)C ZEZGEMKPVIDDHY-UHFFFAOYSA-N 0.000 description 6
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 6
- 239000012346 acetyl chloride Substances 0.000 description 6
- 239000012455 biphasic mixture Substances 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
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- RFIOZSIHFNEKFF-UHFFFAOYSA-M piperazine-1-carboxylate Chemical compound [O-]C(=O)N1CCNCC1 RFIOZSIHFNEKFF-UHFFFAOYSA-M 0.000 description 6
- 239000004033 plastic Substances 0.000 description 6
- KNBZBXCCUDRUIK-UHFFFAOYSA-N pyridine-3-carboxylic acid;dihydrochloride Chemical compound Cl.Cl.OC(=O)C1=CC=CN=C1 KNBZBXCCUDRUIK-UHFFFAOYSA-N 0.000 description 6
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- 125000006239 protecting group Chemical group 0.000 description 4
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- 125000001424 substituent group Chemical group 0.000 description 4
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- WEKGQNRDGWGPTP-PHIMTYICSA-N (2R,6S)-1,2,6-trimethyl-4-pyridin-3-ylpiperazine Chemical compound C[C@H]1CN(C[C@H](N1C)C)C=1C=NC=CC=1 WEKGQNRDGWGPTP-PHIMTYICSA-N 0.000 description 3
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- 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
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- C07D—HETEROCYCLIC COMPOUNDS
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- 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
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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| EP3291809B1 (en) | 2015-05-07 | 2021-08-25 | CHDI Foundation, Inc. | Histone deacetylase inhibitors and compositions and methods of use thereof |
| EP3291810B1 (en) | 2015-05-07 | 2022-08-10 | CHDI Foundation, Inc. | Histone deacetylase inhibitors and compositions and methods of use thereof |
| KR101799009B1 (ko) | 2015-07-27 | 2017-11-17 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 아마이드 유도체 화합물 및 이를 포함하는 약제학적 조성물 |
| RU2697665C1 (ru) | 2015-07-27 | 2019-08-16 | Чонг Кун Данг Фармасьютикал Корп. | Производные 1,3,4-оксадиазолсульфонамида в качестве ингибиторов деацетилазы гистонов 6 и фармацевтическая композиция, содержащая их |
| MY194018A (en) | 2015-07-27 | 2022-11-08 | Chong Kun Dang Pharmaceutical Corp | 1,3,4-oxadiazole sulfamide derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same |
| EP3331864B1 (en) | 2015-08-04 | 2021-11-03 | Chong Kun Dang Pharmaceutical Corp. | 1,3,4-oxadiazole derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same |
| AU2016338118B2 (en) | 2015-10-12 | 2019-03-14 | Chong Kun Dang Pharmaceutical Corp. | Oxadiazole amine derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same |
| WO2018165520A1 (en) | 2017-03-10 | 2018-09-13 | Vps-3, Inc. | Metalloenzyme inhibitor compounds |
| US10435399B2 (en) | 2017-07-31 | 2019-10-08 | Takeda Pharmaceutical Company Limited | HDAC6 inhibitory heterocyclic compound |
| KR102059027B1 (ko) * | 2018-01-12 | 2019-12-24 | 주식회사 비엔에이치리서치 | Hdac6 억제제를 유효성분으로 포함하는 가려움증 예방 또는 치료용 약제학적 조성물 |
| KR102316234B1 (ko) * | 2018-07-26 | 2021-10-22 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이를 포함하는 약제학적 조성물 |
| WO2020158762A1 (ja) | 2019-01-30 | 2020-08-06 | 武田薬品工業株式会社 | 複素環化合物 |
| ES2984772T3 (es) | 2019-04-17 | 2024-10-31 | Quimatryx S L | Derivados de 1,3,4-oxadiazol como inhibidores de histona desacetilasas |
| JP7451569B2 (ja) | 2019-05-31 | 2024-03-18 | チョン クン ダン ファーマシューティカル コーポレーション | ヒストン脱アセチル化酵素６阻害剤としての１，３，４－オキサジアゾールホモフタルイミド誘導体化合物、およびそれを含む薬剤学的組成物 |
| AU2020302928A1 (en) | 2019-06-27 | 2022-02-03 | Medstar Health, Inc. | HDAC6-activated macrophages, compositions, and uses thereof |
| TWI882012B (zh) * | 2019-09-27 | 2025-05-01 | 日商武田藥品工業股份有限公司 | 雜環化合物 |
| WO2021127643A1 (en) | 2019-12-20 | 2021-06-24 | Tenaya Therapeutics, Inc. | Fluoroalkyl-oxadiazoles and uses thereof |
| KR102537616B1 (ko) * | 2020-02-25 | 2023-05-26 | 주식회사 종근당 | 히스톤 탈아세틸화 효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이를 포함하는 약제학적 조성물 |
| JP7571276B2 (ja) * | 2020-07-14 | 2024-10-22 | チョン クン ダン ファーマシューティカル コーポレイション | ヒストン脱アセチル化酵素６阻害剤としての新規な構造の化合物およびこれを含む薬剤学的組成物 |
| CA3189738A1 (en) | 2020-08-07 | 2022-02-10 | Italfarmaco S.P.A. | Novel oxadiazole-based selective hdac6 inhibitors |
| CA3211625A1 (en) * | 2021-04-08 | 2022-10-13 | Chang Sik Lee | 1,3,4-oxadiazole thiocarbonyl compounds as histone deacetylase 6 inhibitor, and pharmaceutical composition comprising the same |
| JP2024514356A (ja) | 2021-04-23 | 2024-04-01 | テナヤ セラピューティクス， インコーポレイテッド | 拡張型心筋症の治療に使用するためのｈｄａｃ６阻害剤 |
| KR20240016950A (ko) * | 2021-05-04 | 2024-02-06 | 테나야 테라퓨틱스, 인코포레이티드 | 대사 질환 및 hfpef의 치료에 사용하기 위한 2-플루오로알킬-1,3,4-옥사디아졸-5-일-티아졸, hdac6 억제제 |
| US20250171433A1 (en) * | 2022-02-08 | 2025-05-29 | Georgetown University | A1h-benzo[c][1,2]thiadiazine-2,2-dioxides bearing heterocyclic linkers as selective histone deacetylase 6 inhibitors |
| TW202412772A (zh) | 2022-07-19 | 2024-04-01 | 義大利商義大利藥品股份有限公司 | 作為選擇性組蛋白去乙醯酶６抑制劑之１，３，４－㗁二唑衍生物 |
| IL318498A (en) | 2022-08-08 | 2025-03-01 | Italfarmaco Spa | Difluoro- and trifluoroacetyl hydrazides as selective HDAC6 inhibitors |
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| TW202426439A (zh) * | 2022-10-14 | 2024-07-01 | 韓商鐘根堂股份有限公司 | 作為組蛋白去乙醯酶6抑制劑之磺醯亞胺化合物以及含彼之醫藥組合物 |
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