TWI694074B - 作為組蛋白去乙醯酶６抑制劑之１,３,４-㗁二唑磺醯胺衍生物及含彼之醫藥組合物 - Google Patents
作為組蛋白去乙醯酶６抑制劑之１,３,４-㗁二唑磺醯胺衍生物及含彼之醫藥組合物 Download PDFInfo
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- TWI694074B TWI694074B TW105123853A TW105123853A TWI694074B TW I694074 B TWI694074 B TW I694074B TW 105123853 A TW105123853 A TW 105123853A TW 105123853 A TW105123853 A TW 105123853A TW I694074 B TWI694074 B TW I694074B
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- methyl
- alkyl
- mmol
- sulfonamide
- reaction mixture
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 14
- -1 1,3,4-oxadiazole sulfamide derivative compounds Chemical class 0.000 title description 136
- 229940122617 Histone deacetylase 6 inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 238
- 150000003839 salts Chemical class 0.000 claims abstract description 56
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 48
- 201000010099 disease Diseases 0.000 claims abstract description 43
- 102000003964 Histone deacetylase Human genes 0.000 claims abstract description 22
- 108090000353 Histone deacetylase Proteins 0.000 claims abstract description 22
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 12
- 239000003814 drug Substances 0.000 claims abstract description 9
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 6
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 6
- 230000001404 mediated effect Effects 0.000 claims abstract description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims abstract description 4
- 206010008805 Chromosomal abnormalities Diseases 0.000 claims abstract description 4
- 208000031404 Chromosome Aberrations Diseases 0.000 claims abstract description 4
- 208000035473 Communicable disease Diseases 0.000 claims abstract description 4
- 206010010356 Congenital anomaly Diseases 0.000 claims abstract description 4
- 230000003542 behavioural effect Effects 0.000 claims abstract description 4
- 208000010643 digestive system disease Diseases 0.000 claims abstract description 4
- 208000016097 disease of metabolism Diseases 0.000 claims abstract description 4
- 230000002124 endocrine Effects 0.000 claims abstract description 4
- 208000030172 endocrine system disease Diseases 0.000 claims abstract description 4
- 230000036244 malformation Effects 0.000 claims abstract description 4
- 230000003340 mental effect Effects 0.000 claims abstract description 4
- 210000002346 musculoskeletal system Anatomy 0.000 claims abstract description 4
- 208000023504 respiratory system disease Diseases 0.000 claims abstract description 4
- 210000002808 connective tissue Anatomy 0.000 claims abstract 2
- 206010033675 panniculitis Diseases 0.000 claims abstract 2
- 210000004304 subcutaneous tissue Anatomy 0.000 claims abstract 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical class NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-UHFFFAOYSA-N 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 125000004434 sulfur atom Chemical group 0.000 claims description 5
- ZVXKYWHJBYIYNI-UHFFFAOYSA-N 1h-pyrazole-4-carboxamide Chemical class NC(=O)C=1C=NNC=1 ZVXKYWHJBYIYNI-UHFFFAOYSA-N 0.000 claims 6
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 239000000203 mixture Substances 0.000 abstract description 68
- 108010023925 Histone Deacetylase 6 Proteins 0.000 abstract description 32
- 238000000034 method Methods 0.000 abstract description 22
- 230000002401 inhibitory effect Effects 0.000 abstract description 11
- 238000002360 preparation method Methods 0.000 abstract description 8
- 230000002265 prevention Effects 0.000 abstract description 4
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 102000011427 Histone Deacetylase 6 Human genes 0.000 abstract 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 708
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 680
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 495
- 239000000243 solution Substances 0.000 description 386
- 239000011541 reaction mixture Substances 0.000 description 305
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 262
- 229920006395 saturated elastomer Polymers 0.000 description 241
- 235000019439 ethyl acetate Nutrition 0.000 description 227
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 214
- 238000000605 extraction Methods 0.000 description 192
- 239000012044 organic layer Substances 0.000 description 192
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 189
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 174
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 169
- 229910004298 SiO 2 Inorganic materials 0.000 description 161
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 147
- 239000007787 solid Substances 0.000 description 135
- 239000011780 sodium chloride Substances 0.000 description 131
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 126
- 238000004587 chromatography analysis Methods 0.000 description 123
- YNBADRVTZLEFNH-UHFFFAOYSA-N methyl nicotinate Chemical compound COC(=O)C1=CC=CN=C1 YNBADRVTZLEFNH-UHFFFAOYSA-N 0.000 description 122
- 238000006243 chemical reaction Methods 0.000 description 119
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 100
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine hydrate Chemical compound O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 description 84
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 83
- 235000017557 sodium bicarbonate Nutrition 0.000 description 83
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 78
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 77
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 74
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 68
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 64
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 60
- 230000002829 reductive effect Effects 0.000 description 56
- 239000002904 solvent Substances 0.000 description 56
- DWXLVZSMXXCSMJ-UHFFFAOYSA-N piperazine-1-sulfonamide Chemical compound NS(=O)(=O)N1CCNCC1 DWXLVZSMXXCSMJ-UHFFFAOYSA-N 0.000 description 55
- 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
- 229940124530 sulfonamide Drugs 0.000 description 53
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 50
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 48
- 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 46
- CWXPZXBSDSIRCS-UHFFFAOYSA-N tert-butyl piperazine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCNCC1 CWXPZXBSDSIRCS-UHFFFAOYSA-N 0.000 description 46
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 39
- 238000000746 purification Methods 0.000 description 38
- 235000019270 ammonium chloride Nutrition 0.000 description 37
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 33
- 150000001335 aliphatic alkanes Chemical class 0.000 description 32
- 239000012043 crude product Substances 0.000 description 32
- 102100022537 Histone deacetylase 6 Human genes 0.000 description 29
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 28
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 24
- 238000003756 stirring Methods 0.000 description 22
- 230000008859 change Effects 0.000 description 21
- 230000000694 effects Effects 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- 238000010992 reflux Methods 0.000 description 20
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 18
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-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
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 16
- 239000002253 acid Substances 0.000 description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 13
- 150000002148 esters Chemical class 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- 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
- 239000002002 slurry Substances 0.000 description 11
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 11
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-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
- 229940095102 methyl benzoate Drugs 0.000 description 10
- NYTDLUUDHUJBJW-UHFFFAOYSA-N piperazine-1-sulfonamide;hydrochloride Chemical compound Cl.NS(=O)(=O)N1CCNCC1 NYTDLUUDHUJBJW-UHFFFAOYSA-N 0.000 description 10
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 9
- WARCRYXKINZHGQ-UHFFFAOYSA-N benzohydrazide Chemical compound NNC(=O)C1=CC=CC=C1 WARCRYXKINZHGQ-UHFFFAOYSA-N 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 239000012230 colorless oil Substances 0.000 description 9
- 239000007788 liquid Substances 0.000 description 9
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 9
- 235000001968 nicotinic acid Nutrition 0.000 description 9
- 239000011664 nicotinic acid Substances 0.000 description 9
- 229960003512 nicotinic acid Drugs 0.000 description 9
- 229910000027 potassium carbonate Inorganic materials 0.000 description 9
- ROADCYAOHVSOLQ-UHFFFAOYSA-N 3-oxetanone Chemical compound O=C1COC1 ROADCYAOHVSOLQ-UHFFFAOYSA-N 0.000 description 8
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 8
- 239000005711 Benzoic acid Substances 0.000 description 8
- 229930040373 Paraformaldehyde Natural products 0.000 description 8
- 150000001412 amines Chemical class 0.000 description 8
- 235000010233 benzoic acid Nutrition 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 8
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 8
- 229920002866 paraformaldehyde Polymers 0.000 description 8
- UTPSYBWCOVZREX-UHFFFAOYSA-N piperazine-1-sulfonamide dihydrochloride Chemical compound Cl.Cl.N1(CCNCC1)S(=O)(=O)N UTPSYBWCOVZREX-UHFFFAOYSA-N 0.000 description 8
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 8
- 239000003276 histone deacetylase inhibitor Substances 0.000 description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N hydrazine group Chemical group NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 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
- WNPFDMGMNSMOMD-UHFFFAOYSA-M 1-imidazol-1-ylsulfonyl-3-methylimidazol-3-ium;trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C1=[N+](C)C=CN1S(=O)(=O)N1C=NC=C1 WNPFDMGMNSMOMD-UHFFFAOYSA-M 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
- 125000000217 alkyl group Chemical group 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
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000004033 plastic Substances 0.000 description 6
- 230000002194 synthesizing effect Effects 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- SHQSVMDWKBRBGB-UHFFFAOYSA-N cyclobutanone Chemical compound O=C1CCC1 SHQSVMDWKBRBGB-UHFFFAOYSA-N 0.000 description 5
- LVYSVCVDBBEQEB-UHFFFAOYSA-N methyl 4-[(3-chloro-4-fluoro-N-piperazin-1-ylsulfonylanilino)methyl]benzoate hydrochloride Chemical compound Cl.COC(=O)c1ccc(CN(c2ccc(F)c(Cl)c2)S(=O)(=O)N2CCNCC2)cc1 LVYSVCVDBBEQEB-UHFFFAOYSA-N 0.000 description 5
- YRQCLNOYFTTWJY-UHFFFAOYSA-N methyl 4-[(N-[methyl(2-piperazin-1-ylethyl)sulfamoyl]anilino)methyl]benzoate Chemical class COC(=O)C1=CC=C(CN(C2=CC=CC=C2)S(=O)(=O)N(C)CCN2CCNCC2)C=C1 YRQCLNOYFTTWJY-UHFFFAOYSA-N 0.000 description 5
- QAFDOZLXNKUWCI-UHFFFAOYSA-N methyl 4-[(N-piperazin-1-ylsulfonylanilino)methyl]benzoate hydrochloride Chemical compound Cl.COC(=O)c1ccc(CN(c2ccccc2)S(=O)(=O)N2CCNCC2)cc1 QAFDOZLXNKUWCI-UHFFFAOYSA-N 0.000 description 5
- USBPOEAFLLEEHP-UHFFFAOYSA-N methyl 6-[(3-chloro-4-fluoro-N-piperazin-1-ylsulfonylanilino)methyl]pyridine-3-carboxylate hydrochloride Chemical compound Cl.COC(=O)c1ccc(CN(c2ccc(F)c(Cl)c2)S(=O)(=O)N2CCNCC2)nc1 USBPOEAFLLEEHP-UHFFFAOYSA-N 0.000 description 5
- 229940050176 methyl chloride Drugs 0.000 description 5
- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 5
- 150000003335 secondary amines Chemical class 0.000 description 5
- 150000003456 sulfonamides Chemical class 0.000 description 5
- ASRHZFWROABGOC-UHFFFAOYSA-N thiomorpholine-4-sulfonamide Chemical compound NS(=O)(=O)N1CCSCC1 ASRHZFWROABGOC-UHFFFAOYSA-N 0.000 description 5
- 108010033040 Histones Proteins 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 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
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 4
- QSNWHKSIIWBAFP-UHFFFAOYSA-N methyl 6-[(3-chloro-N-piperazin-1-ylsulfonylanilino)methyl]pyridine-3-carboxylate hydrochloride Chemical compound Cl.COC(=O)c1ccc(CN(c2cccc(Cl)c2)S(=O)(=O)N2CCNCC2)nc1 QSNWHKSIIWBAFP-UHFFFAOYSA-N 0.000 description 4
- XPZLXLGSSXJCGG-UHFFFAOYSA-N methyl 6-[(N-piperazin-1-ylsulfonylanilino)methyl]pyridine-3-carboxylate dihydrochloride Chemical compound Cl.Cl.COC(=O)c1ccc(CN(c2ccccc2)S(=O)(=O)N2CCNCC2)nc1 XPZLXLGSSXJCGG-UHFFFAOYSA-N 0.000 description 4
- 201000001119 neuropathy Diseases 0.000 description 4
- 230000007823 neuropathy Effects 0.000 description 4
- 208000033808 peripheral neuropathy Diseases 0.000 description 4
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 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
- FWVSUNGWEKSBQM-UHFFFAOYSA-M tert-butyl 4-(3-methylimidazol-3-ium-1-yl)sulfonylpiperazine-1-carboxylate trifluoromethanesulfonate Chemical compound [O-]S(=O)(=O)C(F)(F)F.C[n+]1ccn(c1)S(=O)(=O)N1CCN(CC1)C(=O)OC(C)(C)C FWVSUNGWEKSBQM-UHFFFAOYSA-M 0.000 description 4
- 230000004572 zinc-binding Effects 0.000 description 4
- PNPCRKVUWYDDST-UHFFFAOYSA-N 3-chloroaniline Chemical compound NC1=CC=CC(Cl)=C1 PNPCRKVUWYDDST-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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- NEVUTCKQFWCPDN-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-4-cyclobutyl-N-[[4-(hydrazinecarbonyl)phenyl]methyl]piperazine-1-sulfonamide Chemical compound ClC=1C=C(C=CC=1F)N(S(=O)(=O)N1CCN(CC1)C1CCC1)CC1=CC=C(C=C1)C(=O)NN NEVUTCKQFWCPDN-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
- FIPORMSJLVMZAQ-UHFFFAOYSA-N N-(3-chloro-4-fluorophenyl)-N-[[5-(hydrazinecarbonyl)pyridin-2-yl]methyl]-1,1-dioxo-1,4-thiazinane-4-sulfonamide Chemical compound ClC=1C=C(C=CC=1F)N(S(=O)(=O)N1CCS(CC1)(=O)=O)CC1=NC=C(C=C1)C(=O)NN FIPORMSJLVMZAQ-UHFFFAOYSA-N 0.000 description 3
- CQQDVYKFQAQZNJ-UHFFFAOYSA-N N-(4-fluorophenyl)-N-[[4-(hydrazinecarbonyl)phenyl]methyl]morpholine-4-sulfonamide Chemical compound FC1=CC=C(C=C1)N(S(=O)(=O)N1CCOCC1)CC1=CC=C(C=C1)C(=O)NN CQQDVYKFQAQZNJ-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
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
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- C—CHEMISTRY; METALLURGY
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Families Citing this family (36)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA035592B1 (ru) | 2015-05-07 | 2020-07-13 | Сиэйчдиай Фаундэйшн, Инк. | Ингибиторы деацетилаз гистонов и композиции и способы их применения |
| CA2984618C (en) | 2015-05-07 | 2024-01-09 | Chdi Foundation, Inc. | Histone deacetylase inhibitors and compositions and methods of use thereof |
| 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 |
| HRP20230052T1 (hr) | 2015-07-27 | 2023-03-03 | Chong Kun Dang Pharmaceutical Corp. | Spojevi derivata 1,3,4-oksadiazol sulfonamida kao inhibitori histonske deacetilaze 6, i farmaceutski pripravak koji ih sadrži |
| BR112017027798B1 (pt) | 2015-07-27 | 2023-12-19 | Chong Kun Dang Pharmaceutical Corp | Compostos de derivado de 1,3,4-oxadiazol sulfamida como inibidor de histona desacetilase 6 e a composição farmacêutica que compreende os mesmos |
| HRP20220003T1 (hr) | 2015-08-04 | 2022-04-01 | Chong Kun Dang Pharmaceutical Corp. | Spojevi derivata 1,3,4-oksadiazola kao inhibitori histonske deacetilaze 6, i farmaceutski pripravak koji ih sadrži |
| FI3362445T3 (fi) | 2015-10-12 | 2023-03-21 | Chong Kun Dang Pharmaceutical Corp | Oksadiatsoliamiinijohdannaisyhdisteitä histonideasetylaasi 6:n inhibiittoreina ja niitä käsittävä farmaseuttinen koostumus |
| US10357493B2 (en) | 2017-03-10 | 2019-07-23 | Selenity Therapeutics (Bermuda), Ltd. | Metalloenzyme inhibitor compounds |
| US10435399B2 (en) | 2017-07-31 | 2019-10-08 | Takeda Pharmaceutical Company Limited | HDAC6 inhibitory heterocyclic compound |
| KR102059027B1 (ko) * | 2018-01-12 | 2019-12-24 | 주식회사 비엔에이치리서치 | Hdac6 억제제를 유효성분으로 포함하는 가려움증 예방 또는 치료용 약제학적 조성물 |
| KR102316234B1 (ko) * | 2018-07-26 | 2021-10-22 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 유도체 화합물 및 이를 포함하는 약제학적 조성물 |
| EP3919055A4 (en) * | 2019-01-30 | 2022-11-09 | Takeda Pharmaceutical Company Limited | HETEROCYCLIC COMPOUND |
| AU2020259100B2 (en) * | 2019-04-17 | 2024-12-12 | Fundación Kertor | 1,3,4-oxadiazole derivatives as histone deacetylase inhibitors |
| CN113874369B (zh) | 2019-05-31 | 2024-08-27 | 株式会社钟根堂 | 作为组蛋白脱乙酰酶6抑制剂的1,3,4-噁二唑高邻苯二甲酰亚胺衍生化合物及包含其的药物组合物 |
| CN115443329A (zh) | 2019-06-27 | 2022-12-06 | 乔治华盛顿大学国会特许非营利公司 | Hdac6激活的巨噬细胞、其组合物及用途 |
| CN114727974A (zh) | 2019-07-30 | 2022-07-08 | 艾科尼佐治疗股份有限公司 | Hdac6抑制剂及其用途 |
| CN114846012B (zh) | 2019-09-27 | 2024-01-26 | 武田药品工业株式会社 | 可用作hdac6抑制剂的2-异吲哚-1,3,4-噁二唑衍生物 |
| KR20220119653A (ko) | 2019-12-20 | 2022-08-30 | 테나야 테라퓨틱스, 인코포레이티드 | 플루오로알킬-옥사디아졸 및 이의 용도 |
| 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 |
| 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 |
| KR102504830B1 (ko) * | 2020-07-14 | 2023-03-02 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 새로운 구조의 화합물 및 이를 포함하는 약제학적 조성물 |
| CA3189738A1 (en) | 2020-08-07 | 2022-02-10 | Italfarmaco S.P.A. | Novel oxadiazole-based selective hdac6 inhibitors |
| KR102685058B1 (ko) | 2020-09-02 | 2024-07-15 | 주식회사 종근당 | 히스톤 탈아세틸화효소 6 억제제로서의 새로운 구조의 화합물 및 이를 포함하는 약제학적 조성물 |
| WO2022169985A1 (en) | 2021-02-03 | 2022-08-11 | Eikonizo Therapeutics, Inc. | Hdac6 inhibitors and uses thereof |
| 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 |
| EP4326263A1 (en) | 2021-04-23 | 2024-02-28 | Tenaya Therapeutics, Inc. | Hdac6 inhibitors for use in the treatment of dilated cardiomyopathy |
| US20240252502A1 (en) | 2021-05-04 | 2024-08-01 | Tenaya Therapeutics, Inc. | Hdac6 inhibitors for treatment of metabolic disease and hfpef |
| CA3243781A1 (en) * | 2022-02-08 | 2023-08-17 | Georgetown University | 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 |
| AU2023250964A1 (en) | 2022-04-08 | 2024-11-07 | Eikonizo Therapeutics, Inc. | Oxadiazole hdac6 inhibitors and uses thereof |
| 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 |
| EP4584263A4 (en) * | 2022-09-08 | 2026-06-17 | Chong Kun Dang Pharmaceutical Corp | 1,3,4-OXADIAZOLE DERIVATIVES USED AS HISTONE DEACETYLASE 6 INHIBITORS AND THEIR USES |
| JP2025533206A (ja) * | 2022-10-14 | 2025-10-03 | チョン クン ダン ファーマシューティカル コーポレイション | ヒストンデアセチラーゼ６阻害剤としてのスルホキシイミン化合物及びそれを含む医薬組成物 |
| 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 |
Family Cites Families (52)
| 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 |
| US6897220B2 (en) | 2001-09-14 | 2005-05-24 | Methylgene, Inc. | Inhibitors of histone deacetylase |
| US7868204B2 (en) | 2001-09-14 | 2011-01-11 | Methylgene Inc. | Inhibitors of histone deacetylase |
| MXPA04003169A (es) | 2001-10-03 | 2004-07-08 | Pharmacia Corp | Profarmacos de compuestos policiclicos sustituidos utiles para inhibicion selectiva de la cascada de coagulacion. |
| DK1465861T3 (da) | 2001-12-20 | 2009-08-31 | Bristol Myers Squibb Co | Alpha-(N-sulfonamid)acetamidderivater som beta-amyloidhæmmere |
| CA2615105A1 (en) | 2005-07-14 | 2007-01-25 | Takeda San Diego, Inc. | Histone deacetylase inhibitors |
| US7345178B2 (en) | 2005-08-04 | 2008-03-18 | Sirtris Pharmaceuticals, Inc. | Sirtuin modulating compounds |
| 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 |
| PL1996180T3 (pl) | 2006-03-23 | 2012-05-31 | Biota Scient Management Pty Ltd | Pochodne benzamidu i pirydyloamidu jako czynniki antybakteryjne |
| US20070293530A1 (en) * | 2006-06-14 | 2007-12-20 | Methylgene Inc. | Sulfamide and sulfamate derivatives as histone deacetylase inhibitors |
| 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 |
| JP2010512407A (ja) | 2006-12-11 | 2010-04-22 | ジェネンテック インコーポレイテッド | 新生物を処置するための組成物および方法 |
| 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 |
| 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 |
| SG185925A1 (en) | 2007-11-02 | 2012-12-28 | Momenta Pharmaceuticals Inc | Non-anticoagulant polysaccharide compositions |
| EP2321264B1 (en) | 2008-07-23 | 2016-05-04 | President and Fellows of Harvard College | Deacetylase inhibitors and uses thereof |
| WO2010123933A1 (en) | 2009-04-20 | 2010-10-28 | 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 |
| JP5838157B2 (ja) | 2009-07-22 | 2015-12-24 | ザ・ボード・オブ・トラスティーズ・オブ・ザ・ユニバーシティ・オブ・イリノイＴｈｅ Ｂｏａｒｄ Ｏｆ Ｔｒｕｓｔｅｅｓ Ｏｆ Ｔｈｅ Ｕｎｉｖｅｒｓｉｔｙ Ｏｆ Ｉｌｌｉｎｏｉｓ | Ｈｄａｃ阻害剤およびそれを用いる治療法 |
| KR101781663B1 (ko) | 2010-01-13 | 2017-09-25 | 템페로 파마슈티칼즈, 인크. | 히스톤 데아세틸라제 효소를 억제하기 위한 화합물 및 이를 제조하는 방법 |
| EP2523664A4 (en) * | 2010-01-13 | 2013-06-26 | Tempero Pharmaceuticals Inc | COMPOUNDS AND METHODS |
| PL2526093T3 (pl) | 2010-01-22 | 2017-02-28 | Acetylon Pharmaceuticals, Inc. | Odwrócone związki amidowe jako inhibitory deacetylazy białkowej oraz sposoby ich stosowania |
| BR112012021476A2 (pt) | 2010-02-25 | 2019-09-24 | Piramal Entpr Ltd | composto, processo para preparação do composto, composição farmacêutica compreendendo uma quantidade terapeuticamente eficaz do composto e emprego de tal composto |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| JP5836367B2 (ja) | 2010-05-12 | 2015-12-24 | バーテックス ファーマシューティカルズ インコーポレイテッドＶｅｒｔｅｘ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃｏｒｐｏｒａｔｅｄ | Ａｔｒキナーゼ阻害剤として有用な化合物 |
| US8697739B2 (en) | 2010-07-29 | 2014-04-15 | Novartis Ag | Bicyclic acetyl-CoA carboxylase inhibitors and uses thereof |
| RU2601550C2 (ru) | 2010-12-09 | 2016-11-10 | Вокхардт Лимитед | Кетолидные соединения |
| KR101262870B1 (ko) | 2011-01-28 | 2013-05-09 | 환인제약 주식회사 | 호장근 추출물을 함유하는 호흡기 질환의 예방 또는 치료용 조성물 |
| EA201490228A1 (ru) | 2011-07-08 | 2014-08-29 | Новартис Аг | Новые производные трифторметилоксадиазола и их применение для лечения заболевания |
| EP2734500A4 (en) | 2011-07-20 | 2015-04-08 | Gen Hospital Corp | SELECTIVE HISTONDEACETYLASE-6 INHIBITORS FOR THE TREATMENT OF BONE DISORDERS |
| WO2013041407A1 (en) | 2011-09-19 | 2013-03-28 | Cellzome Ag | Hydroxamic acids as hdac6 inhibitors |
| WO2013052110A1 (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 |
| WO2013066838A1 (en) | 2011-10-31 | 2013-05-10 | Glaxosmithkline Llc | Compounds and methods |
| WO2013066835A2 (en) | 2011-10-31 | 2013-05-10 | Glaxosmithkline Llc | Compounds and methods |
| WO2013066839A2 (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 |
| CA2856334A1 (en) | 2011-11-28 | 2013-06-06 | Christina Hebach | Novel trifluoromethyl-oxadiazole derivatives and their use in the treatment of disease |
| EP2785720B1 (en) | 2011-11-29 | 2017-08-09 | Nanjing Allgen Pharma Co. Ltd. | Heterocyclic amides compounds which are hdac6 inhibitors and used as anti-tumoral agents |
| EP2822926A4 (en) | 2012-03-07 | 2015-11-04 | H Lee Moffitt Cancer Ct & Res | SELECTIVE HISTON DEACTY LASE-6 HEMMER |
| TR201811077T4 (tr) | 2013-09-06 | 2018-08-27 | Aurigene Discovery Tech Ltd | İmmünomodülatörler olarak 1,3,4-oksadiazol ve 1,3,4-tiyadiyazol türevleri. |
| HRP20181965T1 (hr) * | 2013-12-12 | 2019-02-08 | Chong Kun Dang Pharmaceutical Corp. | Novi derivati azaindola kao selektivni inhibitori histonske deacetilaze (hdac) i farmaceutski pripravci koji ih sadrže |
| 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 |
| ES2713700T3 (es) * | 2014-11-24 | 2019-05-23 | Medifron Dbt Inc | Derivados de carboxamida y urea a base de oxazol y tiazol sustituidos como ligandos del receptor de vainilloide II |
| 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 |
| BR112017027798B1 (pt) | 2015-07-27 | 2023-12-19 | Chong Kun Dang Pharmaceutical Corp | Compostos de derivado de 1,3,4-oxadiazol sulfamida como inibidor de histona desacetilase 6 e a composição farmacêutica que compreende os mesmos |
| HRP20230052T1 (hr) * | 2015-07-27 | 2023-03-03 | Chong Kun Dang Pharmaceutical Corp. | Spojevi derivata 1,3,4-oksadiazol sulfonamida kao inhibitori histonske deacetilaze 6, i farmaceutski pripravak koji ih sadrži |
| 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 |
| HRP20220003T1 (hr) | 2015-08-04 | 2022-04-01 | Chong Kun Dang Pharmaceutical Corp. | Spojevi derivata 1,3,4-oksadiazola kao inhibitori histonske deacetilaze 6, i farmaceutski pripravak koji ih sadrži |
| FI3362445T3 (fi) | 2015-10-12 | 2023-03-21 | Chong Kun Dang Pharmaceutical Corp | Oksadiatsoliamiinijohdannaisyhdisteitä histonideasetylaasi 6:n inhibiittoreina ja niitä käsittävä farmaseuttinen koostumus |
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