HETEROARYL COMPOUNDS USEFUL AS INHIBITORS OF E1 ACTIVATING ENZYMES

摘要

Disclosed are heteroaryl sulphonamides as represented by the general formula (I), wherein Ring A is a 6-membered nitrogen-containing heteroaryl ring, optionally fused to a 5- or 6-membered aryl, heteroaryl, cycloaliphatic or heterocyclic ring, wherein either or both rings are optionally substituted and one ring nitrogen atom is optionally oxidized; W is CH2, CHF, CF2, CH(R1), CF(R1), NH, N(R1), O, S, or NHC(O); X is CH2, CHF, CF2, NH, or O; Y is O, S, or C(Rm)(Rn); and wherein the remaining substituents are as defined herein. Representative compounds as disclosed herein include [(1R,2R,3S,4R)-4-({ 6-[(1S)-2,3-dihydro-1H-inden-1-ylamino]pyrimidin-4-yl} amino)-2,3-dihydroxycyclopentyl]methyl sulfamate, [(1R,2R,3S,4R)-2,3-dihydroxy-4-(9H-purin-6-ylamino)cyclopentyl]methyl sulfamate and [(1R,2R,3S,4R)-4-({ 4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-1,3,5-triazin-2-yl} amino)-2,3-dihydroxycyclopentyl]methyl sulfamate. Further disclosed is a pharmaceutical composition, which comprises a compound as defined above and a pharmaceutically acceptable carrier for treating cancer, an immune response disorder or a vascular cell proliferation disorder.