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
- Publication number
- 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
- Authority
- RU
- Russia
- Prior art keywords
- mmol
- methyl
- sulfonamide
- alkyl
- stirred
- Prior art date
Links
- 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
- UVVZJWAYADASDN-UHFFFAOYSA-N 1-(3-chloro-4-fluorophenyl)-4-cyclobutylpiperazine Chemical compound ClC=1C=C(C=CC=1F)N1CCN(CC1)C1CCC1 UVVZJWAYADASDN-UHFFFAOYSA-N 0.000 description 6
- 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
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 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
- 230000005855 radiation Effects 0.000 description 6
- 150000001243 acetic acids Chemical class 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 5
- NLWBJPPMPLPZIE-UHFFFAOYSA-N methyl 4-(bromomethyl)benzoate Chemical compound COC(=O)C1=CC=C(CBr)C=C1 NLWBJPPMPLPZIE-UHFFFAOYSA-N 0.000 description 5
- 201000001119 neuropathy Diseases 0.000 description 5
- 230000007823 neuropathy Effects 0.000 description 5
- 208000033808 peripheral neuropathy Diseases 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 150000003335 secondary amines Chemical class 0.000 description 5
- DFMBSQZAWARSBI-AOOOYVTPSA-N (3S,5R)-3,5-dimethyl-1-pyridin-3-ylpiperazine Chemical compound C[C@H]1CN(C[C@H](N1)C)C=1C=NC=CC=1 DFMBSQZAWARSBI-AOOOYVTPSA-N 0.000 description 4
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- BJBOWDALRUFJLC-UHFFFAOYSA-N N-[[2-fluoro-4-(hydrazinecarbonyl)phenyl]methyl]-4-(oxetan-3-yl)-N-phenylpiperazine-1-sulfonamide Chemical compound FC1=C(CN(S(=O)(=O)N2CCN(CC2)C2COC2)C2=CC=CC=C2)C=CC(=C1)C(=O)NN BJBOWDALRUFJLC-UHFFFAOYSA-N 0.000 description 4
- ZZYMXJMHXUUOIL-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-phenyl-2,7-diazaspiro[3.5]nonane-7-sulfonamide hydrochloride Chemical compound Cl.FC(F)c1nnc(o1)-c1ccc(CN(c2ccccc2)S(=O)(=O)N2CCC3(CNC3)CC2)cc1 ZZYMXJMHXUUOIL-UHFFFAOYSA-N 0.000 description 4
- TXDXMESLKFPIPG-UHFFFAOYSA-N N-[[5-(hydrazinecarbonyl)pyridin-2-yl]methyl]-4-(oxetan-3-yl)-N-phenylpiperazine-1-sulfonamide Chemical compound N(N)C(=O)C=1C=CC(=NC=1)CN(S(=O)(=O)N1CCN(CC1)C1COC1)C1=CC=CC=C1 TXDXMESLKFPIPG-UHFFFAOYSA-N 0.000 description 4
- 208000012902 Nervous system disease Diseases 0.000 description 4
- 208000025966 Neurological disease Diseases 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 125000006239 protecting group Chemical group 0.000 description 4
- 238000006268 reductive amination reaction Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
- 125000004434 sulfur atom Chemical group 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 230000004572 zinc-binding Effects 0.000 description 4
- 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
- KFYVGMJUWPJVKR-OKILXGFUSA-N (2S,6R)-2,6-dimethyl-4-phenyl-1-propylpiperazine Chemical compound C[C@H]1CN(C[C@H](N1CCC)C)C1=CC=CC=C1 KFYVGMJUWPJVKR-OKILXGFUSA-N 0.000 description 3
- UWFMKHYRFAMSRG-TXEJJXNPSA-N (2r,6s)-1,2,6-trimethyl-4-phenylpiperazine Chemical compound C1[C@@H](C)N(C)[C@@H](C)CN1C1=CC=CC=C1 UWFMKHYRFAMSRG-TXEJJXNPSA-N 0.000 description 3
- PPWCLGXCFRCCNO-CQSZACIVSA-N (3R)-N-(3-chlorophenyl)-N-[[5-(hydrazinecarbonyl)pyridin-2-yl]methyl]-3,4-dimethylpiperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1)N(S(=O)(=O)N1C[C@H](N(CC1)C)C)CC1=NC=C(C=C1)C(=O)NN PPWCLGXCFRCCNO-CQSZACIVSA-N 0.000 description 3
- HBPXHBOXPPFFLL-HDICACEKSA-N (3R,5S)-4-ethyl-N-[[4-(hydrazinecarbonyl)phenyl]methyl]-3,5-dimethyl-N-phenylpiperazine-1-sulfonamide Chemical compound C(C)N1[C@H](CN(C[C@H]1C)S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C=C1)C(=O)NN)C HBPXHBOXPPFFLL-HDICACEKSA-N 0.000 description 3
- PPWCLGXCFRCCNO-AWEZNQCLSA-N (3S)-N-(3-chlorophenyl)-N-[[5-(hydrazinecarbonyl)pyridin-2-yl]methyl]-3,4-dimethylpiperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1)N(S(=O)(=O)N1C[C@@H](N(CC1)C)C)CC1=NC=C(C=C1)C(=O)NN PPWCLGXCFRCCNO-AWEZNQCLSA-N 0.000 description 3
- NRNMQRZXSDAUNV-CALCHBBNSA-N (3S,5R)-4-acetyl-N-[[4-(hydrazinecarbonyl)phenyl]methyl]-3,5-dimethyl-N-phenylpiperazine-1-sulfonamide Chemical compound C(C)(=O)N1[C@H](CN(C[C@H]1C)S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C=C1)C(=O)NN)C NRNMQRZXSDAUNV-CALCHBBNSA-N 0.000 description 3
- XANKMFKGBYYKEO-IYBDPMFKSA-N (3S,5R)-4-acetyl-N-[[5-(hydrazinecarbonyl)pyridin-2-yl]methyl]-3,5-dimethyl-N-phenylpiperazine-1-sulfonamide Chemical compound C(C)(=O)N1[C@H](CN(C[C@H]1C)S(=O)(=O)N(C1=CC=CC=C1)CC1=NC=C(C=C1)C(=O)NN)C XANKMFKGBYYKEO-IYBDPMFKSA-N 0.000 description 3
- PGIDISFWNCCCQU-CALCHBBNSA-N (3S,5R)-4-ethyl-N-[[5-(hydrazinecarbonyl)pyridin-2-yl]methyl]-3,5-dimethyl-N-phenylpiperazine-1-sulfonamide Chemical compound C(C)N1[C@H](CN(C[C@H]1C)S(=O)(=O)N(C1=CC=CC=C1)CC1=NC=C(C=C1)C(=O)NN)C PGIDISFWNCCCQU-CALCHBBNSA-N 0.000 description 3
- GTKRJDLEJFQFSO-CALCHBBNSA-N (3S,5R)-N-[[4-(hydrazinecarbonyl)phenyl]methyl]-3,4,5-trimethyl-N-phenylpiperazine-1-sulfonamide Chemical compound N(N)C(=O)C1=CC=C(CN(S(=O)(=O)N2C[C@@H](N([C@@H](C2)C)C)C)C2=CC=CC=C2)C=C1 GTKRJDLEJFQFSO-CALCHBBNSA-N 0.000 description 3
- IVSXPSZVWKOGIV-KDURUIRLSA-N (3S,5R)-N-[[4-(hydrazinecarbonyl)phenyl]methyl]-3,5-dimethyl-N-phenyl-4-propylpiperazine-1-sulfonamide Chemical compound N(N)C(=O)C1=CC=C(CN(S(=O)(=O)N2C[C@@H](N([C@@H](C2)C)CCC)C)C2=CC=CC=C2)C=C1 IVSXPSZVWKOGIV-KDURUIRLSA-N 0.000 description 3
- ZKYIQAJCERVIED-IYBDPMFKSA-N (3S,5R)-N-[[4-(hydrazinecarbonyl)phenyl]methyl]-3,5-dimethyl-N-phenylpiperazine-1-sulfonamide Chemical compound N(N)C(=O)C1=CC=C(CN(S(=O)(=O)N2C[C@@H](N[C@@H](C2)C)C)C2=CC=CC=C2)C=C1 ZKYIQAJCERVIED-IYBDPMFKSA-N 0.000 description 3
- DMOAMYCSRCBVRO-UHFFFAOYSA-N 1-(3-chlorophenyl)-4-cyclobutylpiperazine Chemical compound ClC=1C=C(C=CC=1)N1CCN(CC1)C1CCC1 DMOAMYCSRCBVRO-UHFFFAOYSA-N 0.000 description 3
- FRKOAZXAWJHVIL-PHIMTYICSA-N 1-[(2S,6R)-2,6-dimethyl-4-pyridin-3-ylpiperazin-1-yl]ethanone Chemical compound C(C)(=O)N1[C@H](CN(C[C@H]1C)C=1C=NC=CC=1)C FRKOAZXAWJHVIL-PHIMTYICSA-N 0.000 description 3
- SUBIUPDHPUVLDD-UHFFFAOYSA-N 1-cyclobutyl-4-phenylpiperazine Chemical compound C1CCC1N1CCN(C=2C=CC=CC=2)CC1 SUBIUPDHPUVLDD-UHFFFAOYSA-N 0.000 description 3
- WQDDXVGJRSTLED-UHFFFAOYSA-N 1-methyl-4-phenylpiperazine Chemical compound C1CN(C)CCN1C1=CC=CC=C1 WQDDXVGJRSTLED-UHFFFAOYSA-N 0.000 description 3
- KRNQNTPUHRIZIE-UHFFFAOYSA-N 1-phenyl-4-propan-2-ylpiperazine Chemical compound C1CN(C(C)C)CCN1C1=CC=CC=C1 KRNQNTPUHRIZIE-UHFFFAOYSA-N 0.000 description 3
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-UHFFFAOYSA-N 0.000 description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 3
- ADPVULAMOJBHGF-UHFFFAOYSA-N 4-[(N-[2-(4-acetylpiperazin-1-yl)ethyl-methylsulfamoyl]anilino)methyl]benzohydrazide Chemical compound CN(S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C(=O)NN)C=C1)CCN1CCN(CC1)C(C)=O ADPVULAMOJBHGF-UHFFFAOYSA-N 0.000 description 3
- SBXSUPAFTJURQE-UHFFFAOYSA-N 4-[(N-[methyl-[2-(4-methylpiperazin-1-yl)ethyl]sulfamoyl]anilino)methyl]benzohydrazide Chemical compound CN(S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C(=O)NN)C=C1)CCN1CCN(CC1)C SBXSUPAFTJURQE-UHFFFAOYSA-N 0.000 description 3
- AGOLKFPMNFSBIE-UHFFFAOYSA-N 4-[(N-[methyl-[2-(4-methylsulfonylpiperazin-1-yl)ethyl]sulfamoyl]anilino)methyl]benzohydrazide Chemical compound CN(S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C(=O)NN)C=C1)CCN1CCN(CC1)S(=O)(=O)C AGOLKFPMNFSBIE-UHFFFAOYSA-N 0.000 description 3
- LHMLTYHGTLLHLM-UHFFFAOYSA-N 4-[(N-[methyl-[2-[4-(oxetan-3-yl)piperazin-1-yl]ethyl]sulfamoyl]anilino)methyl]benzohydrazide Chemical compound CN(S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C(=O)NN)C=C1)CCN1CCN(CC1)C1COC1 LHMLTYHGTLLHLM-UHFFFAOYSA-N 0.000 description 3
- YALRMXKAJOCAOY-UHFFFAOYSA-N 4-cyclobutyl-N-[[4-(hydrazinecarbonyl)phenyl]methyl]-N-phenylpiperazine-1-sulfonamide Chemical compound C1(CCC1)N1CCN(CC1)S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C=C1)C(=O)NN YALRMXKAJOCAOY-UHFFFAOYSA-N 0.000 description 3
- CQXKCHQUVFFRFJ-UHFFFAOYSA-N 4-imidazol-1-ylsulfonyl-1,4-thiazinane 1,1-dioxide Chemical compound N1(C=NC=C1)S(=O)(=O)N1CCS(CC1)(=O)=O CQXKCHQUVFFRFJ-UHFFFAOYSA-N 0.000 description 3
- OLQHDKQJHKZUNN-UHFFFAOYSA-N 4-phenyl-1,4-thiazinane 1,1-dioxide Chemical compound C1CS(=O)(=O)CCN1C1=CC=CC=C1 OLQHDKQJHKZUNN-UHFFFAOYSA-N 0.000 description 3
- VWXHJCRMAHDCOE-UHFFFAOYSA-N ClC=1C=C(C=CC=1F)N1CCN(CC1)C Chemical compound ClC=1C=C(C=CC=1F)N1CCN(CC1)C VWXHJCRMAHDCOE-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- KBTBAVGKRMIBGG-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-1,1-dioxo-1,4-thiazinane-4-sulfonamide Chemical compound ClC=1C=C(C=CC=1F)NS(=O)(=O)N1CCS(CC1)(=O)=O KBTBAVGKRMIBGG-UHFFFAOYSA-N 0.000 description 3
- SCYXOMNNCFFUKR-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-N-[[4-(hydrazinecarbonyl)phenyl]methyl]-4-methylpiperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1F)N(S(=O)(=O)N1CCN(CC1)C)CC1=CC=C(C=C1)C(=O)NN SCYXOMNNCFFUKR-UHFFFAOYSA-N 0.000 description 3
- WUTBVTKGRISCEY-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-N-[[4-(hydrazinecarbonyl)phenyl]methyl]-4-propan-2-ylpiperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1F)N(S(=O)(=O)N1CCN(CC1)C(C)C)CC1=CC=C(C=C1)C(=O)NN WUTBVTKGRISCEY-UHFFFAOYSA-N 0.000 description 3
- BEESKMIESFQATF-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-N-[[5-(hydrazinecarbonyl)pyridin-2-yl]methyl]-4-propan-2-ylpiperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1F)N(S(=O)(=O)N1CCN(CC1)C(C)C)CC1=NC=C(C=C1)C(=O)NN BEESKMIESFQATF-UHFFFAOYSA-N 0.000 description 3
- XOKMXDBQCPAIAD-UHFFFAOYSA-N N-[[2-fluoro-4-[[(2,2,2-trifluoroacetyl)amino]carbamoyl]phenyl]methyl]-4-(oxetan-3-yl)-N-phenylpiperazine-1-sulfonamide Chemical compound FC1=C(CN(S(=O)(=O)N2CCN(CC2)C2COC2)C2=CC=CC=C2)C=CC(=C1)C(=O)NNC(C(F)(F)F)=O XOKMXDBQCPAIAD-UHFFFAOYSA-N 0.000 description 3
- MQKGWPGZGHLHIS-UHFFFAOYSA-N N-[[4-(hydrazinecarbonyl)phenyl]methyl]-4-(oxetan-3-yl)-N-phenylpiperazine-1-sulfonamide Chemical compound N(N)C(=O)C1=CC=C(CN(S(=O)(=O)N2CCN(CC2)C2COC2)C2=CC=CC=C2)C=C1 MQKGWPGZGHLHIS-UHFFFAOYSA-N 0.000 description 3
- FFIHKZARVLWSBF-UHFFFAOYSA-N N-[[4-(hydrazinecarbonyl)phenyl]methyl]-N-phenyl-4-propan-2-ylpiperazine-1-sulfonamide Chemical compound N(N)C(=O)C1=CC=C(CN(S(=O)(=O)N2CCN(CC2)C(C)C)C2=CC=CC=C2)C=C1 FFIHKZARVLWSBF-UHFFFAOYSA-N 0.000 description 3
- IHINKXGILMAZFH-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-4-methyl-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC(=C(CN(S(=O)(=O)N2CCN(CC2)C)C2=CC=CC=C2)C=C1)F)F IHINKXGILMAZFH-UHFFFAOYSA-N 0.000 description 3
- AINBCYKSGSHONS-UHFFFAOYSA-N N-[[4-[[(2,2-difluoroacetyl)amino]carbamoyl]-2-fluorophenyl]methyl]-4-(oxetan-3-yl)-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C(=O)NNC(=O)C1=CC(=C(CN(S(=O)(=O)N2CCN(CC2)C2COC2)C2=CC=CC=C2)C=C1)F)F AINBCYKSGSHONS-UHFFFAOYSA-N 0.000 description 3
- FOPLASVJJVASDO-UHFFFAOYSA-N N-[[5-(hydrazinecarbonyl)pyridin-2-yl]methyl]-1,1-dioxo-N-phenyl-1,4-thiazinane-4-sulfonamide Chemical compound N(N)C(=O)C=1C=CC(=NC=1)CN(S(=O)(=O)N1CCS(CC1)(=O)=O)C1=CC=CC=C1 FOPLASVJJVASDO-UHFFFAOYSA-N 0.000 description 3
- XDEVYCJFXACEHC-UHFFFAOYSA-N N-[[5-(hydrazinecarbonyl)pyridin-2-yl]methyl]-4-methyl-N-phenylpiperazine-1-sulfonamide Chemical compound N(N)C(=O)C=1C=CC(=NC=1)CN(S(=O)(=O)N1CCN(CC1)C)C1=CC=CC=C1 XDEVYCJFXACEHC-UHFFFAOYSA-N 0.000 description 3
- KICXPSMHEVWYGF-UHFFFAOYSA-N N-[[5-[[(2,2-difluoroacetyl)amino]carbamoyl]pyridin-2-yl]methyl]-1,1-dioxo-N-phenyl-1,4-thiazinane-4-sulfonamide Chemical compound FC(C(=O)NNC(=O)C=1C=CC(=NC=1)CN(S(=O)(=O)N1CCS(CC1)(=O)=O)C1=CC=CC=C1)F KICXPSMHEVWYGF-UHFFFAOYSA-N 0.000 description 3
- BNSGQDTZFBNXHD-UHFFFAOYSA-N N-[[5-[[(2,2-difluoroacetyl)amino]carbamoyl]pyridin-2-yl]methyl]-4-methyl-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C(=O)NNC(=O)C=1C=CC(=NC=1)CN(S(=O)(=O)N1CCN(CC1)C)C1=CC=CC=C1)F BNSGQDTZFBNXHD-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- MOBCWOUSSISGBJ-UHFFFAOYSA-N methyl 4-(anilinomethyl)benzoate Chemical compound C1=CC(C(=O)OC)=CC=C1CNC1=CC=CC=C1 MOBCWOUSSISGBJ-UHFFFAOYSA-N 0.000 description 3
- OJBQAHZJVDWSFD-UHFFFAOYSA-N methyl 4-(bromomethyl)-3-fluorobenzoate Chemical compound COC(=O)C1=CC=C(CBr)C(F)=C1 OJBQAHZJVDWSFD-UHFFFAOYSA-N 0.000 description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
- 201000006417 multiple sclerosis Diseases 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- NVBFHJWHLNUMCV-UHFFFAOYSA-N sulfamide Chemical group NS(N)(=O)=O NVBFHJWHLNUMCV-UHFFFAOYSA-N 0.000 description 3
- DNYNOAZZKBMKEY-QGZVFWFLSA-N tert-butyl (2R)-4-[(3-chlorophenyl)-[(5-methoxycarbonylpyridin-2-yl)methyl]sulfamoyl]-2-methylpiperazine-1-carboxylate Chemical compound ClC=1C=C(C=CC=1)N(S(=O)(=O)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)CC1=NC=C(C=C1)C(=O)OC DNYNOAZZKBMKEY-QGZVFWFLSA-N 0.000 description 3
- VTFFRINHSSWGGS-GFCCVEGCSA-N tert-butyl (2R)-4-[(3-chlorophenyl)sulfamoyl]-2-methylpiperazine-1-carboxylate Chemical compound ClC=1C=C(C=CC=1)NS(=O)(=O)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C VTFFRINHSSWGGS-GFCCVEGCSA-N 0.000 description 3
- DBKFFTQNQUMCCG-LJQANCHMSA-N tert-butyl (2R)-4-[(5-methoxycarbonylpyridin-2-yl)methyl-(3-methylphenyl)sulfamoyl]-2-methylpiperazine-1-carboxylate Chemical compound COC(=O)C=1C=CC(=NC=1)CN(S(=O)(=O)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C)C=1C=C(C=CC=1)C DBKFFTQNQUMCCG-LJQANCHMSA-N 0.000 description 3
- AZYSTQVBQRUVBG-LLVKDONJSA-N tert-butyl (2R)-4-imidazol-1-ylsulfonyl-2-methylpiperazine-1-carboxylate Chemical compound N1(C=NC=C1)S(=O)(=O)N1C[C@H](N(CC1)C(=O)OC(C)(C)C)C AZYSTQVBQRUVBG-LLVKDONJSA-N 0.000 description 3
- JXUODWWRSLAQRB-BGYRXZFFSA-N tert-butyl (2R,6S)-4-[(4-methoxycarbonylphenyl)methyl-phenylsulfamoyl]-2,6-dimethylpiperazine-1-carboxylate Chemical compound COC(=O)C1=CC=C(CN(S(=O)(=O)N2C[C@@H](N([C@@H](C2)C)C(=O)OC(C)(C)C)C)C2=CC=CC=C2)C=C1 JXUODWWRSLAQRB-BGYRXZFFSA-N 0.000 description 3
- CBOTWIPHDYJGCT-KDURUIRLSA-N tert-butyl (2R,6S)-4-[(4-methoxycarbonylphenyl)methyl-pyridin-3-ylsulfamoyl]-2,6-dimethylpiperazine-1-carboxylate Chemical compound COC(=O)C1=CC=C(CN(S(=O)(=O)N2C[C@@H](N([C@@H](C2)C)C(=O)OC(C)(C)C)C)C=2C=NC=CC=2)C=C1 CBOTWIPHDYJGCT-KDURUIRLSA-N 0.000 description 3
- GDHQMKXMTLIWIX-KDURUIRLSA-N tert-butyl (2R,6S)-4-[(5-methoxycarbonylpyridin-2-yl)methyl-phenylsulfamoyl]-2,6-dimethylpiperazine-1-carboxylate Chemical compound COC(=O)C=1C=CC(=NC=1)CN(S(=O)(=O)N1C[C@@H](N([C@@H](C1)C)C(=O)OC(C)(C)C)C)C1=CC=CC=C1 GDHQMKXMTLIWIX-KDURUIRLSA-N 0.000 description 3
- DNYNOAZZKBMKEY-KRWDZBQOSA-N tert-butyl (2S)-4-[(3-chlorophenyl)-[(5-methoxycarbonylpyridin-2-yl)methyl]sulfamoyl]-2-methylpiperazine-1-carboxylate Chemical compound ClC=1C=C(C=CC=1)N(S(=O)(=O)N1C[C@@H](N(CC1)C(=O)OC(C)(C)C)C)CC1=NC=C(C=C1)C(=O)OC DNYNOAZZKBMKEY-KRWDZBQOSA-N 0.000 description 3
- VTFFRINHSSWGGS-LBPRGKRZSA-N tert-butyl (2S)-4-[(3-chlorophenyl)sulfamoyl]-2-methylpiperazine-1-carboxylate Chemical compound ClC=1C=C(C=CC=1)NS(=O)(=O)N1C[C@@H](N(CC1)C(=O)OC(C)(C)C)C VTFFRINHSSWGGS-LBPRGKRZSA-N 0.000 description 3
- DBKFFTQNQUMCCG-IBGZPJMESA-N tert-butyl (2S)-4-[(5-methoxycarbonylpyridin-2-yl)methyl-(3-methylphenyl)sulfamoyl]-2-methylpiperazine-1-carboxylate Chemical compound COC(=O)C=1C=CC(=NC=1)CN(S(=O)(=O)N1C[C@@H](N(CC1)C(=O)OC(C)(C)C)C)C=1C=C(C=CC=1)C DBKFFTQNQUMCCG-IBGZPJMESA-N 0.000 description 3
- AZYSTQVBQRUVBG-NSHDSACASA-N tert-butyl (2S)-4-imidazol-1-ylsulfonyl-2-methylpiperazine-1-carboxylate Chemical compound N1(C=NC=C1)S(=O)(=O)N1C[C@@H](N(CC1)C(=O)OC(C)(C)C)C AZYSTQVBQRUVBG-NSHDSACASA-N 0.000 description 3
- OSJGNTQIRSHPHD-TXEJJXNPSA-N tert-butyl (2S,6R)-4-imidazol-1-ylsulfonyl-2,6-dimethylpiperazine-1-carboxylate Chemical compound N1(C=NC=C1)S(=O)(=O)N1C[C@@H](N([C@@H](C1)C)C(=O)OC(C)(C)C)C OSJGNTQIRSHPHD-TXEJJXNPSA-N 0.000 description 3
- VRXIOAYUQIITBU-UHFFFAOYSA-N tert-butyl 4-(2-hydroxyethyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(CCO)CC1 VRXIOAYUQIITBU-UHFFFAOYSA-N 0.000 description 3
- CDIHFTFPAMXLPR-UHFFFAOYSA-N tert-butyl 7-(phenylsulfamoyl)-2,7-diazaspiro[3.5]nonane-2-carboxylate Chemical compound C1(=CC=CC=C1)NS(=O)(=O)N1CCC2(CN(C2)C(=O)OC(C)(C)C)CC1 CDIHFTFPAMXLPR-UHFFFAOYSA-N 0.000 description 3
- DHIMTNJVFMCKTP-UHFFFAOYSA-N tert-butyl 7-[(4-methoxycarbonylphenyl)methyl-phenylsulfamoyl]-2,7-diazaspiro[3.5]nonane-2-carboxylate Chemical compound COC(=O)C1=CC=C(CN(S(=O)(=O)N2CCC3(CN(C3)C(=O)OC(C)(C)C)CC2)C2=CC=CC=C2)C=C1 DHIMTNJVFMCKTP-UHFFFAOYSA-N 0.000 description 3
- VTDREWHSMRBXRQ-UHFFFAOYSA-N tert-butyl 7-[[4-(hydrazinecarbonyl)phenyl]methyl-phenylsulfamoyl]-2,7-diazaspiro[3.5]nonane-2-carboxylate Chemical compound N(N)C(=O)C1=CC=C(CN(S(=O)(=O)N2CCC3(CN(C3)C(=O)OC(C)(C)C)CC2)C2=CC=CC=C2)C=C1 VTDREWHSMRBXRQ-UHFFFAOYSA-N 0.000 description 3
- BWHAQEBHTQZIRY-UHFFFAOYSA-N tert-butyl 7-imidazol-1-ylsulfonyl-2,7-diazaspiro[3.5]nonane-2-carboxylate Chemical compound N1(C=NC=C1)S(=O)(=O)N1CCC2(CN(C2)C(=O)OC(C)(C)C)CC1 BWHAQEBHTQZIRY-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- 239000011701 zinc Substances 0.000 description 3
- 229910052725 zinc Inorganic materials 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- JZHCKADNAOZCKV-CQSZACIVSA-N (3R)-N-(3-chlorophenyl)-N-[[5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]methyl]-3,4-dimethylpiperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1)N(S(=O)(=O)N1C[C@H](N(CC1)C)C)CC1=NC=C(C=C1)C=1OC(=NN=1)C(F)F JZHCKADNAOZCKV-CQSZACIVSA-N 0.000 description 2
- XBVNSJOPOYPPEM-IYBDPMFKSA-N (3R,5S)-4-(2,2-difluoroacetyl)-N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-3,5-dimethyl-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C(=O)N1[C@H](CN(C[C@H]1C)S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C=C1)C=1OC(=NN=1)C(F)F)C)F XBVNSJOPOYPPEM-IYBDPMFKSA-N 0.000 description 2
- MPQLERWNCCSZSP-CALCHBBNSA-N (3R,5S)-N-[[5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]methyl]-4-ethyl-3,5-dimethyl-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C=1C=CC(=NC=1)CN(S(=O)(=O)N1C[C@@H](N([C@@H](C1)C)CC)C)C1=CC=CC=C1)F MPQLERWNCCSZSP-CALCHBBNSA-N 0.000 description 2
- JZHCKADNAOZCKV-AWEZNQCLSA-N (3S)-N-(3-chlorophenyl)-N-[[5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]methyl]-3,4-dimethylpiperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1)N(S(=O)(=O)N1C[C@@H](N(CC1)C)C)CC1=NC=C(C=C1)C=1OC(=NN=1)C(F)F JZHCKADNAOZCKV-AWEZNQCLSA-N 0.000 description 2
- SIFPUGLXNQJRKW-IYBDPMFKSA-N (3S,5R)-4-acetyl-N-[[5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]methyl]-3,5-dimethyl-N-phenylpiperazine-1-sulfonamide Chemical compound C(C)(=O)N1[C@H](CN(C[C@H]1C)S(=O)(=O)N(C1=CC=CC=C1)CC1=NC=C(C=C1)C=1OC(=NN=1)C(F)F)C SIFPUGLXNQJRKW-IYBDPMFKSA-N 0.000 description 2
- SHWOZVSIKHTNSB-UHFFFAOYSA-N 1,1-dioxo-N-phenyl-1,4-thiazinane-4-sulfonamide Chemical compound C1(=CC=CC=C1)NS(=O)(=O)N1CCS(CC1)(=O)=O SHWOZVSIKHTNSB-UHFFFAOYSA-N 0.000 description 2
- TUPKOKWZZPSNQQ-UHFFFAOYSA-N 1-(3-chlorophenyl)-4-(oxetan-3-yl)piperazine Chemical compound ClC=1C=C(C=CC=1)N1CCN(CC1)C1COC1 TUPKOKWZZPSNQQ-UHFFFAOYSA-N 0.000 description 2
- VKCBXONEZGIOSP-UHFFFAOYSA-N 1-(4-methylphenyl)sulfonylazetidine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1CCC1 VKCBXONEZGIOSP-UHFFFAOYSA-N 0.000 description 2
- USPZDUMJHUANKM-UHFFFAOYSA-N 1-[4-[2-[[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl-phenylsulfamoyl]-methylamino]ethyl]piperazin-1-yl]ethanone Chemical compound CN(S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C=C1)C=1OC(=NN=1)C(F)F)CCN1CCN(CC1)C(C)=O USPZDUMJHUANKM-UHFFFAOYSA-N 0.000 description 2
- ZLKNPIVTWNMMMH-UHFFFAOYSA-N 1-imidazol-1-ylsulfonylimidazole Chemical compound C1=CN=CN1S(=O)(=O)N1C=CN=C1 ZLKNPIVTWNMMMH-UHFFFAOYSA-N 0.000 description 2
- NWWVDTMFZKRSME-UHFFFAOYSA-N 2-cyclobutyl-N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-phenyl-2,7-diazaspiro[3.5]nonane-7-sulfonamide Chemical compound C1(CCC1)N1CC2(C1)CCN(CC2)S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C=C1)C=1OC(=NN=1)C(F)F NWWVDTMFZKRSME-UHFFFAOYSA-N 0.000 description 2
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 2
- DGMOBVGABMBZSB-UHFFFAOYSA-N 2-methylpropanoyl chloride Chemical compound CC(C)C(Cl)=O DGMOBVGABMBZSB-UHFFFAOYSA-N 0.000 description 2
- CUYKNJBYIJFRCU-UHFFFAOYSA-N 3-aminopyridine Chemical compound NC1=CC=CN=C1 CUYKNJBYIJFRCU-UHFFFAOYSA-N 0.000 description 2
- YSEMCVGMNUUNRK-UHFFFAOYSA-N 3-chloro-4-fluoroaniline Chemical compound NC1=CC=C(F)C(Cl)=C1 YSEMCVGMNUUNRK-UHFFFAOYSA-N 0.000 description 2
- IRMXWQPVXSDKRJ-UHFFFAOYSA-N 4-acetyl-N-[[2-fluoro-4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-phenylpiperazine-1-sulfonamide Chemical compound C(C)(=O)N1CCN(CC1)S(=O)(=O)N(C1=CC=CC=C1)CC1=C(C=C(C=C1)C=1OC(=NN=1)C(F)(F)F)F IRMXWQPVXSDKRJ-UHFFFAOYSA-N 0.000 description 2
- KZVFDDQUTOBPRZ-UHFFFAOYSA-N 4-acetyl-N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-N-phenylpiperazine-1-sulfonamide Chemical compound C(C)(=O)N1CCN(CC1)S(=O)(=O)N(C1=CC=CC=C1)CC1=C(C=C(C=C1)C=1OC(=NN=1)C(F)F)F KZVFDDQUTOBPRZ-UHFFFAOYSA-N 0.000 description 2
- UQPZQERGYWSGSR-UHFFFAOYSA-N 4-cyclobutyl-N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-phenylpiperazine-1-sulfonamide Chemical compound C1(CCC1)N1CCN(CC1)S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C=C1)C=1OC(=NN=1)C(F)F UQPZQERGYWSGSR-UHFFFAOYSA-N 0.000 description 2
- LFMBBMBMQSXRJM-UHFFFAOYSA-N 4-ethyl-N-[[2-fluoro-4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-phenylpiperazine-1-sulfonamide Chemical compound C(C)N1CCN(CC1)S(=O)(=O)N(C1=CC=CC=C1)CC1=C(C=C(C=C1)C=1OC(=NN=1)C(F)(F)F)F LFMBBMBMQSXRJM-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 102000014461 Ataxins Human genes 0.000 description 2
- 108010078286 Ataxins Proteins 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 206010008025 Cerebellar ataxia Diseases 0.000 description 2
- 108010077544 Chromatin Proteins 0.000 description 2
- 206010008805 Chromosomal abnormalities Diseases 0.000 description 2
- 208000031404 Chromosome Aberrations Diseases 0.000 description 2
- 206010009944 Colon cancer Diseases 0.000 description 2
- 208000035473 Communicable disease Diseases 0.000 description 2
- 206010010356 Congenital anomaly Diseases 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- 208000030814 Eating disease Diseases 0.000 description 2
- 208000019454 Feeding and Eating disease Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 102100039869 Histone H2B type F-S Human genes 0.000 description 2
- 108010033040 Histones Proteins 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101001035372 Homo sapiens Histone H2B type F-S Proteins 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- XPMZKRDZZWCBDE-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-4-methylpiperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1F)N(S(=O)(=O)N1CCN(CC1)C)CC1=CC=C(C=C1)C=1OC(=NN=1)C(F)F XPMZKRDZZWCBDE-UHFFFAOYSA-N 0.000 description 2
- ZLUDPFYCVKEKJM-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-4-propan-2-ylpiperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1F)N(S(=O)(=O)N1CCN(CC1)C(C)C)CC1=CC=C(C=C1)C=1OC(=NN=1)C(F)F ZLUDPFYCVKEKJM-UHFFFAOYSA-N 0.000 description 2
- PDWGHKTZSKXPIH-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-N-[[5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]methyl]-4-propan-2-ylpiperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1F)N(S(=O)(=O)N1CCN(CC1)C(C)C)CC1=NC=C(C=C1)C=1OC(=NN=1)C(F)F PDWGHKTZSKXPIH-UHFFFAOYSA-N 0.000 description 2
- MVKSCNPSFAUQTD-UHFFFAOYSA-N N-(3-chlorophenyl)-4-cyclobutyl-N-[[5-(hydrazinecarbonyl)pyridin-2-yl]methyl]piperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1)N(S(=O)(=O)N1CCN(CC1)C1CCC1)CC1=NC=C(C=C1)C(=O)NN MVKSCNPSFAUQTD-UHFFFAOYSA-N 0.000 description 2
- SKERKVZQZGFZSS-UHFFFAOYSA-N N-(3-fluorophenyl)-N-[[2-fluoro-4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-4-methylpiperazine-1-sulfonamide Chemical compound FC1=C(CN(S(=O)(=O)N2CCN(CC2)C)C2=CC(=CC=C2)F)C=CC(=C1)C=1OC(=NN=1)C(F)(F)F SKERKVZQZGFZSS-UHFFFAOYSA-N 0.000 description 2
- YIMYMZMBPHDTOB-UHFFFAOYSA-N N-[[2-fluoro-4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-4-(2-methylpropanoyl)-N-phenylpiperazine-1-sulfonamide Chemical compound FC1=C(CN(S(=O)(=O)N2CCN(CC2)C(C(C)C)=O)C2=CC=CC=C2)C=CC(=C1)C=1OC(=NN=1)C(F)(F)F YIMYMZMBPHDTOB-UHFFFAOYSA-N 0.000 description 2
- STVRPRHLAJSSQQ-UHFFFAOYSA-N N-[[2-fluoro-4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-4-(oxetan-3-yl)-N-phenylpiperazine-1-sulfonamide Chemical compound FC1=C(CN(S(=O)(=O)N2CCN(CC2)C2COC2)C2=CC=CC=C2)C=CC(=C1)C=1OC(=NN=1)C(F)(F)F STVRPRHLAJSSQQ-UHFFFAOYSA-N 0.000 description 2
- RSBWQRJDIHARHV-UHFFFAOYSA-N N-[[2-fluoro-4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-4-methyl-N-phenylpiperazine-1-sulfonamide Chemical compound FC1=C(CN(S(=O)(=O)N2CCN(CC2)C)C2=CC=CC=C2)C=CC(=C1)C=1OC(=NN=1)C(F)(F)F RSBWQRJDIHARHV-UHFFFAOYSA-N 0.000 description 2
- LDFMJPBFTHEUSR-UHFFFAOYSA-N N-[[2-fluoro-4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-4-methylsulfonyl-N-phenylpiperazine-1-sulfonamide Chemical compound FC1=C(CN(S(=O)(=O)N2CCN(CC2)S(=O)(=O)C)C2=CC=CC=C2)C=CC(=C1)C=1OC(=NN=1)C(F)(F)F LDFMJPBFTHEUSR-UHFFFAOYSA-N 0.000 description 2
- KNLBCLIKFPBKPQ-UHFFFAOYSA-N N-[[2-fluoro-4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-phenyl-4-propan-2-ylpiperazine-1-sulfonamide Chemical compound FC1=C(CN(S(=O)(=O)N2CCN(CC2)C(C)C)C2=CC=CC=C2)C=CC(=C1)C=1OC(=NN=1)C(F)(F)F KNLBCLIKFPBKPQ-UHFFFAOYSA-N 0.000 description 2
- QEIVEKWJCSKAMJ-UHFFFAOYSA-N N-[[2-fluoro-4-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-phenyl-4-propanoylpiperazine-1-sulfonamide Chemical compound FC1=C(CN(S(=O)(=O)N2CCN(CC2)C(CC)=O)C2=CC=CC=C2)C=CC(=C1)C=1OC(=NN=1)C(F)(F)F QEIVEKWJCSKAMJ-UHFFFAOYSA-N 0.000 description 2
- PLKNQFMUAVGVMU-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-4-(2-methylpropanoyl)-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC(=C(CN(S(=O)(=O)N2CCN(CC2)C(C(C)C)=O)C2=CC=CC=C2)C=C1)F)F PLKNQFMUAVGVMU-UHFFFAOYSA-N 0.000 description 2
- PEKYQMGJZIOWPR-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-4-(oxetan-3-yl)-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC(=C(CN(S(=O)(=O)N2CCN(CC2)C2COC2)C2=CC=CC=C2)C=C1)F)F PEKYQMGJZIOWPR-UHFFFAOYSA-N 0.000 description 2
- ZHFGKNZMFFXOAB-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-4-ethyl-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC(=C(CN(S(=O)(=O)N2CCN(CC2)CC)C2=CC=CC=C2)C=C1)F)F ZHFGKNZMFFXOAB-UHFFFAOYSA-N 0.000 description 2
- OSYBUQRDBLHASQ-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-4-methyl-N-phenylpiperazine-1-sulfonamide hydrochloride Chemical compound Cl.CN1CCN(CC1)S(=O)(=O)N(Cc1ccc(cc1F)-c1nnc(o1)C(F)F)c1ccccc1 OSYBUQRDBLHASQ-UHFFFAOYSA-N 0.000 description 2
- FCYYFNJSDXLLIR-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-4-methylsulfonyl-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC(=C(CN(S(=O)(=O)N2CCN(CC2)S(=O)(=O)C)C2=CC=CC=C2)C=C1)F)F FCYYFNJSDXLLIR-UHFFFAOYSA-N 0.000 description 2
- XVWLGCIZTWYAEV-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-N-(3-fluorophenyl)-4-methylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC(=C(CN(S(=O)(=O)N2CCN(CC2)C)C2=CC(=CC=C2)F)C=C1)F)F XVWLGCIZTWYAEV-UHFFFAOYSA-N 0.000 description 2
- APCCFMPHZXCYBJ-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-N-phenyl-4-propan-2-ylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC(=C(CN(S(=O)(=O)N2CCN(CC2)C(C)C)C2=CC=CC=C2)C=C1)F)F APCCFMPHZXCYBJ-UHFFFAOYSA-N 0.000 description 2
- SHDRHSLLGSWURU-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]-2-fluorophenyl]methyl]-N-phenyl-4-propanoylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC(=C(CN(S(=O)(=O)N2CCN(CC2)C(CC)=O)C2=CC=CC=C2)C=C1)F)F SHDRHSLLGSWURU-UHFFFAOYSA-N 0.000 description 2
- IGRSBJKSBMNQFY-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-2-(oxetan-3-yl)-N-phenyl-2,7-diazaspiro[3.5]nonane-7-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC=C(CN(S(=O)(=O)N2CCC3(CN(C3)C3COC3)CC2)C2=CC=CC=C2)C=C1)F IGRSBJKSBMNQFY-UHFFFAOYSA-N 0.000 description 2
- WNYVMZOSZOMPAI-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-4-(oxetan-3-yl)-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC=C(CN(S(=O)(=O)N2CCN(CC2)C2COC2)C2=CC=CC=C2)C=C1)F WNYVMZOSZOMPAI-UHFFFAOYSA-N 0.000 description 2
- WYDDEFHNMHADMO-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-[methyl-[2-(4-methylpiperazin-1-yl)ethyl]sulfamoyl]aniline Chemical compound CN(S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C=C1)C=1OC(=NN=1)C(F)F)CCN1CCN(CC1)C WYDDEFHNMHADMO-UHFFFAOYSA-N 0.000 description 2
- UDHJWHNBAFNBAR-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-phenyl-4-propan-2-ylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC=C(CN(S(=O)(=O)N2CCN(CC2)C(C)C)C2=CC=CC=C2)C=C1)F UDHJWHNBAFNBAR-UHFFFAOYSA-N 0.000 description 2
- VMJMRSJTVNYKLJ-UHFFFAOYSA-N N-[[5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]methyl]-1,1-dioxo-N-phenyl-1,4-thiazinane-4-sulfonamide Chemical compound FC(C1=NN=C(O1)C=1C=CC(=NC=1)CN(S(=O)(=O)N1CCS(CC1)(=O)=O)C1=CC=CC=C1)F VMJMRSJTVNYKLJ-UHFFFAOYSA-N 0.000 description 2
- ZVXQLPNREXWDPB-UHFFFAOYSA-N N-[[5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]methyl]-4-(oxetan-3-yl)-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C=1C=CC(=NC=1)CN(S(=O)(=O)N1CCN(CC1)C1COC1)C1=CC=CC=C1)F ZVXQLPNREXWDPB-UHFFFAOYSA-N 0.000 description 2
- TZZYLOQLBZNTEZ-UHFFFAOYSA-N N-[[5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]methyl]-4-methyl-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C=1C=CC(=NC=1)CN(S(=O)(=O)N1CCN(CC1)C)C1=CC=CC=C1)F TZZYLOQLBZNTEZ-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 2
- 208000019498 Skin and subcutaneous tissue disease Diseases 0.000 description 2
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 201000004562 autosomal dominant cerebellar ataxia Diseases 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- WRJWRGBVPUUDLA-UHFFFAOYSA-N chlorosulfonyl isocyanate Chemical compound ClS(=O)(=O)N=C=O WRJWRGBVPUUDLA-UHFFFAOYSA-N 0.000 description 2
- 210000003483 chromatin Anatomy 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 210000002808 connective tissue Anatomy 0.000 description 2
- 238000003381 deacetylation reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 235000014632 disordered eating Nutrition 0.000 description 2
- 208000030172 endocrine system disease Diseases 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 238000007429 general method Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- 230000036244 malformation Effects 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 208000030159 metabolic disease Diseases 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 210000002346 musculoskeletal system Anatomy 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 208000023504 respiratory system disease Diseases 0.000 description 2
- 208000017520 skin disease Diseases 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 208000002320 spinal muscular atrophy Diseases 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- XSBOTWUEDYMRKM-UHFFFAOYSA-N tert-butyl 4-(2-methylsulfonyloxyethyl)piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCN(CCOS(C)(=O)=O)CC1 XSBOTWUEDYMRKM-UHFFFAOYSA-N 0.000 description 2
- MBTADYPUSOMXMY-UHFFFAOYSA-N tert-butyl 7-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl-phenylsulfamoyl]-2,7-diazaspiro[3.5]nonane-2-carboxylate Chemical compound FC(C1=NN=C(O1)C1=CC=C(CN(S(=O)(=O)N2CCC3(CN(C3)C(=O)OC(C)(C)C)CC2)C2=CC=CC=C2)C=C1)F MBTADYPUSOMXMY-UHFFFAOYSA-N 0.000 description 2
- 229940126585 therapeutic drug Drugs 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- WAEXFXRVDQXREF-UHFFFAOYSA-N vorinostat Chemical compound ONC(=O)CCCCCCC(=O)NC1=CC=CC=C1 WAEXFXRVDQXREF-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- GMUDVKDHPFXAED-CALCHBBNSA-N (3S,5R)-4-acetyl-N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-3,5-dimethyl-N-phenylpiperazine-1-sulfonamide Chemical compound C(C)(=O)N1[C@H](CN(C[C@H]1C)S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C=C1)C=1OC(=NN=1)C(F)F)C GMUDVKDHPFXAED-CALCHBBNSA-N 0.000 description 1
- MCDAIVIQTVDVHH-CALCHBBNSA-N (3S,5R)-N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-3,4,5-trimethyl-N-phenylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC=C(CN(S(=O)(=O)N2C[C@@H](N([C@@H](C2)C)C)C)C2=CC=CC=C2)C=C1)F MCDAIVIQTVDVHH-CALCHBBNSA-N 0.000 description 1
- GNPTWAQNSHKVRV-KDURUIRLSA-N (3S,5R)-N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-3,5-dimethyl-N-phenyl-4-propylpiperazine-1-sulfonamide Chemical compound FC(C1=NN=C(O1)C1=CC=C(CN(S(=O)(=O)N2C[C@@H](N([C@@H](C2)C)CCC)C)C2=CC=CC=C2)C=C1)F GNPTWAQNSHKVRV-KDURUIRLSA-N 0.000 description 1
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- KUSYIGBGHPOWEL-UHFFFAOYSA-N 2-methyl nonaoic acid Chemical compound CCCCCCCC(C)C(O)=O KUSYIGBGHPOWEL-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 1
- QZVQQUVWFIZUBQ-UHFFFAOYSA-N 3-fluoroaniline Chemical compound NC1=CC=CC(F)=C1 QZVQQUVWFIZUBQ-UHFFFAOYSA-N 0.000 description 1
- RUCVFOIOCBMGFY-UHFFFAOYSA-N 4-(oxetan-3-yl)-N-phenyl-N-[[5-[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]methyl]piperazine-1-sulfonamide Chemical compound O1CC(C1)N1CCN(CC1)S(=O)(=O)N(CC1=NC=C(C=C1)C=1OC(=NN=1)C(F)(F)F)C1=CC=CC=C1 RUCVFOIOCBMGFY-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 208000022309 Alcoholic Liver disease Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003658 Atrial Fibrillation Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000010061 Autosomal Dominant Polycystic Kidney Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- QBOXDBZSPAEFNL-UHFFFAOYSA-N CC(C)(C)N(CC1)CCN1S(N(CC(C=CC(C(NNC(C(F)(F)F)=O)=O)=C1)=C1F)C1=CC(F)=CC=C1)(=O)=O Chemical compound CC(C)(C)N(CC1)CCN1S(N(CC(C=CC(C(NNC(C(F)(F)F)=O)=O)=C1)=C1F)C1=CC(F)=CC=C1)(=O)=O QBOXDBZSPAEFNL-UHFFFAOYSA-N 0.000 description 1
- GOSPDTSQSOJPSR-UHFFFAOYSA-N CC(C)(C)N(CC1)CCN1S(N(CC(C=CC(C1=NN=C(C(F)(F)F)O1)=C1)=C1F)C1=CC=CN=C1)(=O)=O Chemical compound CC(C)(C)N(CC1)CCN1S(N(CC(C=CC(C1=NN=C(C(F)(F)F)O1)=C1)=C1F)C1=CC=CN=C1)(=O)=O GOSPDTSQSOJPSR-UHFFFAOYSA-N 0.000 description 1
- IBJDMIAFCHZOTJ-UHFFFAOYSA-N CC(C)(C)N(CC1)CCN1S(N(CC(C=CC(C1=NN=C(C(F)F)O1)=C1)=C1F)C1=CC(F)=CC=C1)(=O)=O Chemical compound CC(C)(C)N(CC1)CCN1S(N(CC(C=CC(C1=NN=C(C(F)F)O1)=C1)=C1F)C1=CC(F)=CC=C1)(=O)=O IBJDMIAFCHZOTJ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
- 102000010958 Cortactin Human genes 0.000 description 1
- 108010037663 Cortactin Proteins 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 208000032612 Glial tumor Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 101710113864 Heat shock protein 90 Proteins 0.000 description 1
- 102100034051 Heat shock protein HSP 90-alpha Human genes 0.000 description 1
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 1
- 102100039996 Histone deacetylase 1 Human genes 0.000 description 1
- 102100021454 Histone deacetylase 4 Human genes 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 101001035024 Homo sapiens Histone deacetylase 1 Proteins 0.000 description 1
- 101000899259 Homo sapiens Histone deacetylase 4 Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- JLVVSXFLKOJNIY-UHFFFAOYSA-N Magnesium ion Chemical compound [Mg+2] JLVVSXFLKOJNIY-UHFFFAOYSA-N 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 208000003445 Mouth Neoplasms Diseases 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 208000034578 Multiple myelomas Diseases 0.000 description 1
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 1
- IIBMRSXNBKZXTI-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-4-cyclobutyl-N-[[5-(hydrazinecarbonyl)pyridin-2-yl]methyl]piperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1F)N(S(=O)(=O)N1CCN(CC1)C1CCC1)CC1=NC=C(C=C1)C(=O)NN IIBMRSXNBKZXTI-UHFFFAOYSA-N 0.000 description 1
- FIAZVYIQRLPOGX-UHFFFAOYSA-N N-(3-chlorophenyl)-4-cyclobutyl-N-[[5-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]pyridin-2-yl]methyl]piperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1)N(S(=O)(=O)N1CCN(CC1)C1CCC1)CC1=NC=C(C=C1)C=1OC(=NN=1)C(F)F FIAZVYIQRLPOGX-UHFFFAOYSA-N 0.000 description 1
- GDXILYBAPQUGED-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-[methyl-[2-(4-methylsulfonylpiperazin-1-yl)ethyl]sulfamoyl]aniline Chemical compound CN(S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C=C1)C=1OC(=NN=1)C(F)F)CCN1CCN(CC1)S(=O)(=O)C GDXILYBAPQUGED-UHFFFAOYSA-N 0.000 description 1
- USJBGOJTWAOTTB-UHFFFAOYSA-N N-[[4-[5-(difluoromethyl)-1,3,4-oxadiazol-2-yl]phenyl]methyl]-N-[methyl-[2-[4-(oxetan-3-yl)piperazin-1-yl]ethyl]sulfamoyl]aniline Chemical compound CN(S(=O)(=O)N(C1=CC=CC=C1)CC1=CC=C(C=C1)C=1OC(=NN=1)C(F)F)CCN1CCN(CC1)C1COC1 USJBGOJTWAOTTB-UHFFFAOYSA-N 0.000 description 1
- FUMHCSLIXZRMJU-UHFFFAOYSA-N N-phenylthiomorpholine-4-sulfonamide Chemical compound C1(=CC=CC=C1)NS(=O)(=O)N1CCSCC1 FUMHCSLIXZRMJU-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 206010035226 Plasma cell myeloma Diseases 0.000 description 1
- 102100039388 Polyamine deacetylase HDAC10 Human genes 0.000 description 1
- 101710107444 Polyamine deacetylase HDAC10 Proteins 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 208000006289 Rett Syndrome Diseases 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 102000011990 Sirtuin Human genes 0.000 description 1
- 108050002485 Sirtuin Proteins 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 208000031673 T-Cell Cutaneous Lymphoma Diseases 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- 102000004243 Tubulin Human genes 0.000 description 1
- 108090000704 Tubulin Proteins 0.000 description 1
- 108010005705 Ubiquitinated Proteins Proteins 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 208000018839 Wilson disease Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- IAJILQKETJEXLJ-RSJOWCBRSA-N aldehydo-D-galacturonic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-RSJOWCBRSA-N 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 206010002022 amyloidosis Diseases 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 208000022185 autosomal dominant polycystic kidney disease Diseases 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000003936 benzamides Chemical class 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 1
- 210000004899 c-terminal region Anatomy 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 108020001778 catalytic domains Proteins 0.000 description 1
- 230000025084 cell cycle arrest Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 201000007241 cutaneous T cell lymphoma Diseases 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 230000006196 deacetylation Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000009088 enzymatic function Effects 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 238000012226 gene silencing method Methods 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- QFWPJPIVLCBXFJ-UHFFFAOYSA-N glymidine Chemical compound N1=CC(OCCOC)=CN=C1NS(=O)(=O)C1=CC=CC=C1 QFWPJPIVLCBXFJ-UHFFFAOYSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000006195 histone acetylation Effects 0.000 description 1
- 230000006197 histone deacetylation Effects 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229910001410 inorganic ion Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 1
- 201000007270 liver cancer Diseases 0.000 description 1
- 208000014018 liver neoplasm Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 201000005202 lung cancer Diseases 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- 229910001425 magnesium ion Inorganic materials 0.000 description 1
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 201000005962 mycosis fungoides Diseases 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 230000014399 negative regulation of angiogenesis Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012740 non-selective inhibitor Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 201000002528 pancreatic cancer Diseases 0.000 description 1
- 208000008443 pancreatic carcinoma Diseases 0.000 description 1
- 208000011906 peptic ulcer disease Diseases 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 230000004481 post-translational protein modification Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910001414 potassium ion Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 208000025638 primary cutaneous T-cell non-Hodgkin lymphoma Diseases 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 235000004252 protein component Nutrition 0.000 description 1
- YQUVCSBJEUQKSH-UHFFFAOYSA-N protochatechuic acid Natural products OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- OHRURASPPZQGQM-GCCNXGTGSA-N romidepsin Chemical compound O1C(=O)[C@H](C(C)C)NC(=O)C(=C/C)/NC(=O)[C@H]2CSSCC\C=C\[C@@H]1CC(=O)N[C@H](C(C)C)C(=O)N2 OHRURASPPZQGQM-GCCNXGTGSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- DATRVIMZZZVHMP-MRVPVSSYSA-N tert-butyl (2r)-2-methylpiperazine-1-carboxylate Chemical compound C[C@@H]1CNCCN1C(=O)OC(C)(C)C DATRVIMZZZVHMP-MRVPVSSYSA-N 0.000 description 1
- DATRVIMZZZVHMP-QMMMGPOBSA-N tert-butyl (2s)-2-methylpiperazine-1-carboxylate Chemical compound C[C@H]1CNCCN1C(=O)OC(C)(C)C DATRVIMZZZVHMP-QMMMGPOBSA-N 0.000 description 1
- RBOGBIZGALIITO-DTORHVGOSA-N tert-butyl (2s,6r)-2,6-dimethylpiperazine-1-carboxylate Chemical compound C[C@H]1CNC[C@@H](C)N1C(=O)OC(C)(C)C RBOGBIZGALIITO-DTORHVGOSA-N 0.000 description 1
- HWLNKJXLGQVMJH-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[3.5]nonane-2-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CC21CCNCC2 HWLNKJXLGQVMJH-UHFFFAOYSA-N 0.000 description 1
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- ASRHZFWROABGOC-UHFFFAOYSA-N thiomorpholine-4-sulfonamide Chemical compound NS(=O)(=O)N1CCSCC1 ASRHZFWROABGOC-UHFFFAOYSA-N 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
- 206010044412 transitional cell carcinoma Diseases 0.000 description 1
- 208000023747 urothelial carcinoma Diseases 0.000 description 1
- WKOLLVMJNQIZCI-UHFFFAOYSA-N vanillic acid Chemical compound COC1=CC(C(O)=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-N 0.000 description 1
- TUUBOHWZSQXCSW-UHFFFAOYSA-N vanillic acid Natural products COC1=CC(O)=CC(C(O)=O)=C1 TUUBOHWZSQXCSW-UHFFFAOYSA-N 0.000 description 1
- 229960000237 vorinostat Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/18—Sulfonamides
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D471/10—Spiro-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Obesity (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurology (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR10-2015-0106177 | 2015-07-27 | ||
| KR20150106177 | 2015-07-27 | ||
| PCT/KR2016/008218 WO2017018805A1 (en) | 2015-07-27 | 2016-07-27 | 1,3,4-oxadiazole sulfamide derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2695227C1 RU2695227C1 (ru) | 2019-07-22 |
| RU2695227C9 true RU2695227C9 (ru) | 2020-03-04 |
Family
ID=57885712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018106904A RU2695227C9 (ru) | 2015-07-27 | 2016-07-27 | Производные 1,3,4-оксадиазолсульфамида в качестве ингибитора гистондеацетилазы 6 и содержащая их фармацевтическая композиция |
Country Status (21)
| Country | Link |
|---|---|
| US (1) | US10464911B2 (enExample) |
| EP (1) | EP3328844B1 (enExample) |
| JP (1) | JP6538266B2 (enExample) |
| KR (1) | KR101799005B1 (enExample) |
| CN (1) | CN107980040B (enExample) |
| AU (1) | AU2016299486B2 (enExample) |
| BR (1) | BR112017027798B1 (enExample) |
| CA (1) | CA2987570C (enExample) |
| DK (1) | DK3328844T3 (enExample) |
| ES (1) | ES2774510T3 (enExample) |
| HR (1) | HRP20200280T1 (enExample) |
| HU (1) | HUE048534T2 (enExample) |
| MX (1) | MX376585B (enExample) |
| MY (1) | MY194018A (enExample) |
| NZ (1) | NZ736432A (enExample) |
| PH (1) | PH12017501939B1 (enExample) |
| PL (1) | PL3328844T3 (enExample) |
| PT (1) | PT3328844T (enExample) |
| RU (1) | RU2695227C9 (enExample) |
| TW (1) | TWI694074B (enExample) |
| WO (1) | WO2017018805A1 (enExample) |
Families Citing this family (35)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3291809B1 (en) | 2015-05-07 | 2021-08-25 | CHDI Foundation, Inc. | Histone deacetylase inhibitors and compositions and methods of use thereof |
| WO2016179554A1 (en) | 2015-05-07 | 2016-11-10 | Chdi Foundation, Inc. | Histone deacetylase inhibitors and compositions and methods of use thereof |
| PL3328843T3 (pl) | 2015-07-27 | 2023-02-27 | Chong Kun Dang Pharmaceutical Corp. | Związki będące pochodnymi 1,3,4 oksadiazolosulfonamidów jako inhibitor deacetylazy histonowej 6, oraz kompozycja farmaceutyczna je zawierająca |
| RU2695227C9 (ru) | 2015-07-27 | 2020-03-04 | Чонг Кун Данг Фармасьютикал Корп. | Производные 1,3,4-оксадиазолсульфамида в качестве ингибитора гистондеацетилазы 6 и содержащая их фармацевтическая композиция |
| NZ739211A (en) | 2015-07-27 | 2019-05-31 | Chong Kun Dang Pharmaceutical Corp | 1,3,4-oxadiazole amide derivative compound as histone deacetylase 6 inhibitor, and pharmaceutical composition containing same |
| PT3331864T (pt) | 2015-08-04 | 2022-01-18 | Chong Kun Dang Pharmaceutical Corp | Compostos derivados de 1,3,4-oxadiazol como inibidor de histona desacetilase 6 e a composição farmacêutica compreendendo os mesmos |
| CA3001666C (en) | 2015-10-12 | 2021-03-30 | 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 |
| EP3661931A1 (en) | 2017-07-31 | 2020-06-10 | Takeda Pharmaceutical Company Limited | 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 |
| JP7470058B2 (ja) * | 2019-01-30 | 2024-04-17 | 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 |
| MY207444A (en) | 2019-05-31 | 2025-02-27 | Chong Kun Dang Pharmaceutical Corp | 1,3,4-oxadiazole homophthalimide derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same |
| BR112021026334A2 (pt) | 2019-06-27 | 2022-05-10 | Medstar Health | Macrófagos ativados por hdac6, composições, e usos dos mesmos |
| WO2021021979A2 (en) | 2019-07-30 | 2021-02-04 | Eikonizo Therapapeutics, Inc. | Hdac6 inhibitors and uses thereof |
| AU2020353984B2 (en) | 2019-09-27 | 2025-09-25 | Takeda Pharmaceutical Company Limited | 2-isoindol-1,3,4-oxadiazole derivatives useful as HDAC6 inhibitors |
| CN114980887A (zh) | 2019-12-20 | 2022-08-30 | 特纳亚治疗股份有限公司 | 氟代烷基-噁二唑及其用途 |
| 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 |
| KR102537615B1 (ko) | 2020-02-25 | 2023-05-30 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이를 포함하는 약제학적 조성물 |
| WO2022013728A1 (en) * | 2020-07-14 | 2022-01-20 | Chong Kun Dang Pharmaceutical Corp. | Novel compounds as histone deacetylase 6 inhibitor, and pharmaceutical composition comprising the same |
| PE20231744A1 (es) | 2020-08-07 | 2023-10-31 | Italfarmaco Spa | Nuevos inhibidores selectivos de hdac6 basados en oxadiazol |
| KR102685058B1 (ko) | 2020-09-02 | 2024-07-15 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 새로운 구조의 화합물 및 이를 포함하는 약제학적 조성물 |
| KR102905373B1 (ko) * | 2021-04-08 | 2025-12-29 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 싸이오카보닐 화합물 및 이를 포함하는 약제학적 조성물 |
| IL307883A (en) | 2021-04-23 | 2023-12-01 | Tenaya Therapeutics Inc | HDAC6 inhibitors for use in the treatment of dilated myocardial disease |
| WO2022235842A1 (en) * | 2021-05-04 | 2022-11-10 | Tenaya Therapeutics, Inc. | 2-fluoroalkyl-1,3,4-oxadiazol-5-yl-thiazol, hdac6 inhibitors for use in the treatment of metabolic disease and hfpef |
| EP4475845A4 (en) * | 2022-02-08 | 2025-12-31 | Univ Georgetown | A1H-BENZO[C][1,2]THIADIAZINE-2,2-DIOXIDES BEARING HETEROCYCLIC BONDS AS SELECTIVE HISTONE DEACETYLASE INHIBITORS 6 |
| KR102904231B1 (ko) * | 2022-04-07 | 2025-12-29 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이의 용도 |
| EP4504190A4 (en) | 2022-04-08 | 2026-03-25 | Eikonizo Therapeutics Inc | OXADIAZOLE HDAC6 INHIBITORS AND THEIR USES |
| 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 |
| WO2024033293A1 (en) | 2022-08-08 | 2024-02-15 | Italfarmaco S.P.A. | Difluoro- and trifluoro-acetyl hydrazides as selective hdac6 inhibitors |
| KR20240035172A (ko) * | 2022-09-08 | 2024-03-15 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이의 용도 |
| 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 |
| WO2025215092A1 (en) | 2024-04-10 | 2025-10-16 | Institut National de la Santé et de la Recherche Médicale | Selective hdac6 inhibitors for use in the treatment of myotonic dystrophy type 1 |
| WO2026018065A1 (en) * | 2024-07-18 | 2026-01-22 | Eurofarma Laboratórios S.A. | Hdac-6 inhibiting compounds and treatment of diseases with the same |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070293530A1 (en) * | 2006-06-14 | 2007-12-20 | Methylgene Inc. | Sulfamide and sulfamate derivatives as histone deacetylase inhibitors |
| US20120289495A1 (en) * | 2010-01-13 | 2012-11-15 | Tempero Pharmaceuticals Inc. | Compounds and methods |
| RU2515611C2 (ru) * | 2008-07-23 | 2014-05-20 | Президент Энд Феллоуз Оф Гарвард Колледж | Ингибиторы деацетилазы и их применение |
Family Cites Families (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0276432A3 (de) | 1986-12-12 | 1988-10-26 | Ciba-Geigy Ag | Schädlingsbekämpfungsmittel |
| KR100265385B1 (ko) | 1998-02-27 | 2000-11-01 | 윤여표 | 순환기 질환의 예방 및 치료 효능을 갖는 홍경천 추출물 |
| US7868204B2 (en) | 2001-09-14 | 2011-01-11 | Methylgene Inc. | Inhibitors of histone deacetylase |
| US6897220B2 (en) | 2001-09-14 | 2005-05-24 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| JP2005509606A (ja) | 2001-10-03 | 2005-04-14 | ファルマシア・コーポレーション | 凝血カスケードを選択的に阻害するのに有用な置換された多環式化合物のプロドラッグ |
| ES2325205T3 (es) | 2001-12-20 | 2009-08-28 | Bristol-Myers Squibb Company | Derivados de alfa-(n-sulfonamido)acetamida como inhibidores beta-amiloides. |
| ZA200800901B (en) | 2005-07-14 | 2010-05-26 | Takeda San Diego Inc | Histone deacetylase inhibitors |
| EP1909910A1 (en) | 2005-08-04 | 2008-04-16 | Sirtris Pharmaceuticals, Inc. | Benzimidazole derivatives as sirtuin modulators |
| WO2007032445A1 (ja) | 2005-09-16 | 2007-03-22 | Kyowa Hakko Kogyo Co., Ltd. | タンパク質キナーゼ阻害剤 |
| WO2007107758A1 (en) | 2006-03-23 | 2007-09-27 | Prolysis Ltd | Antibacterial agents |
| EP1878730A1 (en) | 2006-07-12 | 2008-01-16 | Bayer Schering Pharma Aktiengesellschaft | Substituted isoxazolines, pharmaceutical compositions containing the same, methods of preparing the same, and uses of the same |
| WO2008073509A2 (en) | 2006-12-11 | 2008-06-19 | Genentech, Inc. | Compositions and methods for treating a neoplasm |
| WO2009010479A2 (en) | 2007-07-13 | 2009-01-22 | Euroscreen S.A. | Heterocyclic methylene piperidine derivatives and their use |
| KR100903743B1 (ko) | 2007-08-28 | 2009-06-19 | 전병태 | 소화기계 질환개선 및 예방용 식품 조성물 |
| RU2010122324A (ru) | 2007-11-02 | 2011-12-10 | Момента Фармасьютикалз, Инк. (Us) | Полисахаридные композиции, не обладающие антикоагулянтными свойствами |
| BRPI0817897A2 (pt) | 2007-11-02 | 2019-09-24 | Methylgene Inc | composto, composição, e, métodos de inibição da atividade hdac, e de tratamento de uma doença responsiva a um inibidor de atividade hdac |
| US20120136003A1 (en) | 2009-04-20 | 2012-05-31 | Institute For Oneworld Health | Compounds, compositions and methods comprising 1,3,4-oxadiazole derivatives |
| WO2010126002A1 (ja) | 2009-04-28 | 2010-11-04 | 塩野義製薬株式会社 | ヘテロ環スルホンアミド化合物を含有する医薬 |
| JP2011008205A (ja) | 2009-05-27 | 2011-01-13 | Fujifilm Corp | 二軸性光学異方性膜を作製するための組成物 |
| US8431538B2 (en) | 2009-07-22 | 2013-04-30 | The Board Of Trustees Of The University Of Illinois | HDAC inhibitors and therapeutic methods of using same |
| KR101781663B1 (ko) | 2010-01-13 | 2017-09-25 | 템페로 파마슈티칼즈, 인크. | 히스톤 데아세틸라제 효소를 억제하기 위한 화합물 및 이를 제조하는 방법 |
| NZ601655A (en) | 2010-01-22 | 2014-10-31 | Acetylon Pharmaceuticals Inc | Reverse amide compounds as protein deacetylase inhibitors and methods of use thereof |
| CN103108867A (zh) | 2010-02-25 | 2013-05-15 | 皮拉马尔企业有限公司 | 噁二唑化合物及其制备和用途 |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| AU2011253025A1 (en) | 2010-05-12 | 2012-11-29 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| US8697739B2 (en) | 2010-07-29 | 2014-04-15 | Novartis Ag | Bicyclic acetyl-CoA carboxylase inhibitors and uses thereof |
| EP3216798A3 (en) | 2010-12-09 | 2017-10-25 | Wockhardt Limited | Ketolide compounds |
| KR101262870B1 (ko) | 2011-01-28 | 2013-05-09 | 환인제약 주식회사 | 호장근 추출물을 함유하는 호흡기 질환의 예방 또는 치료용 조성물 |
| CN103764635B (zh) | 2011-07-08 | 2016-01-20 | 诺华股份有限公司 | 新的三氟甲基-噁二唑衍生物及其在疾病治疗中的用途 |
| JP6169076B2 (ja) | 2011-07-20 | 2017-07-26 | ザ ジェネラル ホスピタル コーポレイション | 骨疾患の処置のためのヒストン脱アセチル化酵素６選択的阻害剤 |
| WO2013041407A1 (en) | 2011-09-19 | 2013-03-28 | Cellzome Ag | Hydroxamic acids as hdac6 inhibitors |
| CA2850757A1 (en) | 2011-10-03 | 2013-04-11 | The Trustees Of Columbia University In The City Of New York | Novel molecules that selectively inhibit histone deacetylase 6 relative to histone deacetylase 1 |
| WO2013066835A2 (en) | 2011-10-31 | 2013-05-10 | Glaxosmithkline Llc | Compounds and methods |
| WO2013066833A1 (en) | 2011-10-31 | 2013-05-10 | Glaxosmithkline Llc | Compounds and methods to inhibit histone deacetylase (hdac) enzymes |
| WO2013066839A2 (en) | 2011-10-31 | 2013-05-10 | Glaxosmithkline Llc | Compounds and methods |
| WO2013066838A1 (en) | 2011-10-31 | 2013-05-10 | Glaxosmithkline Llc | Compounds and methods |
| EP2785713B1 (en) | 2011-11-28 | 2016-09-07 | Novartis AG | Novel trifluoromethyl-oxadiazole derivatives and their use in the treatment of disease |
| CN103974956B (zh) | 2011-11-29 | 2016-07-06 | 南京奥昭生物科技有限公司 | 作为hdac6抑制剂和用作抗肿瘤剂的杂环酰胺化合物 |
| CA2866707A1 (en) | 2012-03-07 | 2013-09-12 | H. Lee Moffitt Cancer Center And Research Institute, Inc. | Selective histone deactylase 6 inhibitors |
| EP3385257A1 (en) | 2013-09-06 | 2018-10-10 | Aurigene Discovery Technologies Limited | 1,3,4-oxadiazole and 1,3,4-thiadiazole derivatives as immunomodulators |
| EP3080125B1 (en) | 2013-12-12 | 2018-10-10 | Chong Kun Dang Pharmaceutical Corp. | Novel azaindole derivatives as selective histone deacetylase (hdac) inhibitors and pharmaceutical compositions comprising the same |
| CN104744446B (zh) | 2013-12-30 | 2019-06-25 | 广东东阳光药业有限公司 | 杂芳化合物及其在药物中的应用 |
| CN107108593B (zh) | 2014-11-24 | 2020-03-24 | 美迪福伦Dbt有限公司 | 作为类香草素受体配体ii的基于取代的恶唑和噻唑的羧酰胺和脲衍生物 |
| CN106349451B (zh) | 2015-07-14 | 2020-11-13 | 罗门哈斯公司 | 用于制备疏水改性环氧烷氨基甲酸酯聚合物的方法 |
| RU2695227C9 (ru) | 2015-07-27 | 2020-03-04 | Чонг Кун Данг Фармасьютикал Корп. | Производные 1,3,4-оксадиазолсульфамида в качестве ингибитора гистондеацетилазы 6 и содержащая их фармацевтическая композиция |
| NZ739211A (en) | 2015-07-27 | 2019-05-31 | Chong Kun Dang Pharmaceutical Corp | 1,3,4-oxadiazole amide derivative compound as histone deacetylase 6 inhibitor, and pharmaceutical composition containing same |
| PL3328843T3 (pl) * | 2015-07-27 | 2023-02-27 | Chong Kun Dang Pharmaceutical Corp. | Związki będące pochodnymi 1,3,4 oksadiazolosulfonamidów jako inhibitor deacetylazy histonowej 6, oraz kompozycja farmaceutyczna je zawierająca |
| PT3331864T (pt) | 2015-08-04 | 2022-01-18 | Chong Kun Dang Pharmaceutical Corp | Compostos derivados de 1,3,4-oxadiazol como inibidor de histona desacetilase 6 e a composição farmacêutica compreendendo os mesmos |
| CA3001666C (en) | 2015-10-12 | 2021-03-30 | Chong Kun Dang Pharmaceutical Corp. | Oxadiazole amine derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same |
-
2016
- 2016-07-27 RU RU2018106904A patent/RU2695227C9/ru active
- 2016-07-27 WO PCT/KR2016/008218 patent/WO2017018805A1/en not_active Ceased
- 2016-07-27 AU AU2016299486A patent/AU2016299486B2/en active Active
- 2016-07-27 KR KR1020160095326A patent/KR101799005B1/ko active Active
- 2016-07-27 JP JP2018504096A patent/JP6538266B2/ja active Active
- 2016-07-27 MY MYPI2017703935A patent/MY194018A/en unknown
- 2016-07-27 ES ES16830838T patent/ES2774510T3/es active Active
- 2016-07-27 BR BR112017027798-0A patent/BR112017027798B1/pt active IP Right Grant
- 2016-07-27 HR HRP20200280TT patent/HRP20200280T1/hr unknown
- 2016-07-27 CN CN201680025249.5A patent/CN107980040B/zh active Active
- 2016-07-27 TW TW105123853A patent/TWI694074B/zh active
- 2016-07-27 DK DK16830838.5T patent/DK3328844T3/da active
- 2016-07-27 PL PL16830838T patent/PL3328844T3/pl unknown
- 2016-07-27 MX MX2017017090A patent/MX376585B/es active IP Right Grant
- 2016-07-27 CA CA2987570A patent/CA2987570C/en active Active
- 2016-07-27 US US15/747,850 patent/US10464911B2/en active Active
- 2016-07-27 HU HUE16830838A patent/HUE048534T2/hu unknown
- 2016-07-27 EP EP16830838.5A patent/EP3328844B1/en active Active
- 2016-07-27 NZ NZ736432A patent/NZ736432A/en unknown
- 2016-07-27 PT PT168308385T patent/PT3328844T/pt unknown
-
2017
- 2017-10-24 PH PH12017501939A patent/PH12017501939B1/en unknown
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070293530A1 (en) * | 2006-06-14 | 2007-12-20 | Methylgene Inc. | Sulfamide and sulfamate derivatives as histone deacetylase inhibitors |
| RU2515611C2 (ru) * | 2008-07-23 | 2014-05-20 | Президент Энд Феллоуз Оф Гарвард Колледж | Ингибиторы деацетилазы и их применение |
| US20120289495A1 (en) * | 2010-01-13 | 2012-11-15 | Tempero Pharmaceuticals Inc. | Compounds and methods |
Non-Patent Citations (3)
| Title |
|---|
| Manku S. et al. Synthesis and evaluation of lysine derived sulfamides as histone deacetylase inhibitors, Bioorganic & Medicinal Chemistry Letters, 19, 7, стр. 1866-1870, 2009. * |
| Manku S. et al. Synthesis and evaluation of lysine derived sulfamides as histone deacetylase inhibitors, Bioorganic & Medicinal Chemistry Letters, 19, 7, стр. 1866-1870, 2009. Pal, Dilipkumar, Hydroxamic acid - A novel molecule for anticancer therapy, Journal of Advanced Pharmaceutical Technology & Research, 3, 2, стр. 92-99, 2012. * |
| Pal, Dilipkumar, Hydroxamic acid - A novel molecule for anticancer therapy, Journal of Advanced Pharmaceutical Technology & Research, 3, 2, стр. 92-99, 2012. * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2695227C1 (ru) | Производные 1,3,4-оксадиазолсульфамида в качестве ингибитора гистондеацетилазы 6 и содержащая их фармацевтическая композиция | |
| US10584117B2 (en) | 1,3,4-oxadiazole amide derivative compound as histone deacetylase 6 inhibitor, and pharmaceutical composition containing same | |
| US10538498B2 (en) | 1,3,4-oxadiazole sulfonamide derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same | |
| US10287255B2 (en) | Compounds as histone deacetylase 6 inhibitors and pharmaceutical compositions comprising the same | |
| RU2709207C2 (ru) | 1,3,4-оксадиазольные производные соединения в качестве ингибитора гистондеацетилазы 6 и фармацевтическая композиция, содержащая их | |
| US12522601B2 (en) | 1,3,4-oxadiazole derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same | |
| US12466827B2 (en) | 1,3,4-oxadiazole derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same | |
| CN115427406B (zh) | 作为组蛋白脱乙酰酶6抑制剂的1,3,4-噁二唑衍生物化合物以及包含其的药物组合物 | |
| JP7642859B2 (ja) | ヒストン脱アセチル化酵素６阻害剤としての１，３，４－オキサジアゾールチオカルボニル化合物およびこれを含む薬剤学的組成物 | |
| KR20250033306A (ko) | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 트리아졸 화합물 및 이를 포함하는 약제학적 조성물 | |
| RU2858542C2 (ru) | Соединения 1,3,4-оксадиазолтриазола в качестве ингибитора гистондеацетилазы 6 и фармацевтическая композиция, содержащая их | |
| RU2810081C1 (ru) | Производные 1,3,4-оксадиазола в качестве ингибитора гистондеацетилазы 6 и содержащая их фармацевтическая композиция | |
| CA3174319C (en) | 1,3,4-oxadiazole derivative compounds as histone deacetylase 6 inhibitor, and the pharmaceutical composition comprising the same | |
| RU2822624C1 (ru) | Производные 1,3,4-оксадиазола в качестве ингибитора гистондеацетилазы 6 и содержащая их фармацевтическая композиция |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| TH4A | Reissue of patent specification |