Aryl sulfonamides active as 5-HT6 receptor antagonist or serotonin antagonist for the treatment of obesity

摘要

A method of treatment or prophylaxis of obesity, comprising administering to a patient in need of such treatment a therapeutically effective amount of an aryl sulfonamide compound of formula (I) or formula (II) wherein the substituents are as described in the specification in which E is -SO2NH- or -NHSO2. R2 is hydrogen, C1-6 alkyl or arylC1-6alkyl ; P is phenyl, naphthyl a bicyclic heterocyclic ring or is a 5-to 7-membered hererocyclic ring each containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur; A is a single bond, a C1-6 alkylene or a C1-6 alkenylene group; R1 is halogen, C1-6 alkyl, optionally substituted by one or more halogen atoms, C3-6 cycloalkyl, COC1-6 alkyl, C1-6 alkoxy, OCF3, hydroxy, hydroxy C1-6alkyl, hydroxy C1-6alkoxy, C1-6 alkoxy C1-6 alkoxy, C1-6 alkanoyl, acyl, nitro, amino, alkylamino or dialkylamino, cyano or SR11 where R11 is hydrogen or C1-6 alkyl or R1 is phenyl, benzyl, naphthyl, a bicyclic heterocyclic ring, or is a 5 to 7-membered heterocyclic ring, each containing 1 to 4 heteroatoms selected from oxygen, nitrogen or sulfur; n = 0, 1, 2, 3, 4, 5 or 6; R3 is a group R5 or together with R5 forms a group (CH2) or (CH2)3O or R3 is linked to R2 to form a group (CH2)2 or (CH2)3; R4 is-X (CH2)p-R6 where X is a single bond, CH2, O, NH or N-C1-6-alkyl and p = 0 to 6 and R6 is an optionally substituted 5-to 7-membered heterocyclic ring containing 1 to 3 heteroatoms selected from nitrogen, sulfur or oxygen, or R6 is NR7R8 where R7 and R8 are independently hydrogen, C1-6 alkyl or aryl C1-6 alkyl, or R4 is selected from a group of formula (i), (ii) or (iii) wherein in formula (i) R9 is C1-6alkyl, or C1-6alkyl substituted by one or more halogen atoms; m = 0, 1 or 2 ; q = 0, 1, 2, 3 or 4; in formula (ii) wherein R9, m and q are as defined in formula (i); in formula (iii) R9, m and q are as defined in formula (i) and R7 is hydrogen or C1-6alkyl; R5 is hydrogen, halogen, C1-6alkyl, C1-6alkoxy, optionally substituted with one or more fluorine atoms, C3-6 cycloalkyl, COC1-6 alkyl, C1-6 alkoxy, hydroxy, hydroxy C1-6alkyl, hydroxy C1-6alkoxy, C1-6alkoxyC1-6alkoxy, acyl, nitro, trifluoromethyl or together with R3 forms a group (CH2)2O or (CH2)3O, cyano or aryl; or pharmaceutically acceptable salts thereof are disclosed.