ES2774510T3 - Derivados de 1,3,4-oxadiazol sulfamida como inhibidores de histona desacetilasa 6 y composición farmacéutica que comprende los mismos - Google Patents
Derivados de 1,3,4-oxadiazol sulfamida como inhibidores de histona desacetilasa 6 y composición farmacéutica que comprende los mismos Download PDFInfo
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- ES2774510T3 ES2774510T3 ES16830838T ES16830838T ES2774510T3 ES 2774510 T3 ES2774510 T3 ES 2774510T3 ES 16830838 T ES16830838 T ES 16830838T ES 16830838 T ES16830838 T ES 16830838T ES 2774510 T3 ES2774510 T3 ES 2774510T3
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- alkyl
- mmol
- methyl
- sulfonamide
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- 239000008194 pharmaceutical composition Substances 0.000 title claims description 14
- 108010023925 Histone Deacetylase 6 Proteins 0.000 title description 31
- UYJSDFHXPYMBBN-UHFFFAOYSA-N 1,3,4-oxadiazole sulfamide Chemical class NS(N)(=O)=O.c1nnco1 UYJSDFHXPYMBBN-UHFFFAOYSA-N 0.000 title description 9
- 239000003112 inhibitor Substances 0.000 title description 3
- 102000011427 Histone Deacetylase 6 Human genes 0.000 title 1
- -1 1,3,4-oxadiazole sulfamide derivative compound Chemical class 0.000 claims abstract description 236
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 144
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims abstract description 38
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 15
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 9
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 9
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 9
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims abstract description 3
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- 150000001875 compounds Chemical class 0.000 claims description 216
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- JFUIHGAGFMFNRD-UHFFFAOYSA-N fica Chemical compound FC1=CC=C2NC(C(=O)NCCS)=CC2=C1 JFUIHGAGFMFNRD-UHFFFAOYSA-N 0.000 claims 1
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- 125000006242 amine protecting group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 575
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 543
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 447
- 239000000243 solution Substances 0.000 description 350
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 288
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 242
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 226
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 212
- 229920006395 saturated elastomer Polymers 0.000 description 202
- 235000019439 ethyl acetate Nutrition 0.000 description 192
- 239000007787 solid Substances 0.000 description 152
- 238000000605 extraction Methods 0.000 description 150
- 239000012044 organic layer Substances 0.000 description 150
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 144
- 235000019341 magnesium sulphate Nutrition 0.000 description 144
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 141
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 140
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 125
- 239000011780 sodium chloride Substances 0.000 description 121
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 117
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- 229910052682 stishovite Inorganic materials 0.000 description 106
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- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 96
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 80
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 58
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 54
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 40
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 38
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
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- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 5
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