New cinnamoylaminoalkyl-substituted benzenesulfonamide derivatives, are ATP-sensitive potassium channel inhibitors and vagal nervous system stimulants useful for treating cardiovascular disorders

摘要

N-(Cinnamoylaminoalkyl-substituted benzenesulfonyl) carbamate, urea or cyanoguanidine derivatives (I) are new. Benzenesulfonamide derivatives of formula (I), including stereoisomers, stereoisomer mixtures and salts, are new. X = O, S or N-CN; Y = (CHR5)n; Z' = NH or O; A1-A3 = H, halo, alkyl, alkoxy, OCH2O, CHO or CF3; R1 = alkyl; alkoxy (optionally substituted by -E1-alkyl-D1; 4-7 membered heterocyclyl containing 1 or 2 O as heteroatom(s); or Ph'); 2-4C alkenyloxy; OPh'; phenyl (optionally substituted by 1 or 2 of halo, alkyl, alkoxy, S(O)m-alkyl, Ph, NH2, OH, NO2, CF3, CN, COOH, CONH2, alkoxycarbonyl or CHO); 2-5C alkenyl (optionally substituted by Ph, CN, COOH or alkoxycarbonyl); 2-5C alkynyl (optionally substituted by Ph or alkoxy); mono- or bicyclic heterocyclyl containing 1 or 2 of O, S and N as heteroatom(s); -S(O)m-Ph'; or S(O)m-alkyl; D1 = H or E2-alkyl-D2; D2 = H or E3-alkyl; E1-E3 = O, S or NH; R2 = H, 1-6C alkyl or 3-7C cycloalkyl (but not H if Z' = O); R3, R4 = Ph', H or alkyl; R5 = H or 1-3C alkyl; m = 0-2; n = 1-4; Ph' = phenyl (optionally substituted by 1 or 2 of halo, alkyl, alkoxy and CF3); Compounds (I; X = O; Z' = NH; R1 = halo, alkyl or alkoxy; R2 = 2-6C alkyl or 5-7C cycloalkyl) (i.e. (I')) are excluded; alkyl moieties have 1-4C unless specified otherwise. Independent claims are included for the following: (1) the preparation of (I); (2) (I) or (I') (including stereoisomers, stereoisomer mixtures and salts) as agents for inhibiting ATP-sensitive potassium channels or stimulating the vagal nervous system; and (3) some of (I') (including stereoisomers, stereoisomer mixtures and salts) as new compounds, i.e. (I'; R1 = alkoxy; R3, R4 = H or alkyl).