| abstract |
Sulfonamide derivatives of formula (I) having a lipophilic moiety which are substantially soluble and are useful as pharmaceutically active compounds; pharmaceutical formulations containing such sulfonamide derivatives; and methods of their preparation are disclosed, wherein Ar1 is an aryl or heteroaryl groups; Ar2 is thienyl or a furanyl group; X is O or S, preferably O; R1 is hydrogen or a C1-C6-alkyl group, or R1 forms a substituted or unsubstituted 5-6-membered saturated or unsaturated ring with Ar1; n is an integer from 0 to 5, preferably between 1-3 and most preferred 1; Y is a 4-12-membered saturated cyclic or bicyclic alkyl containing at least one nitrogen atom, whereby one nitrogen atom within said ring is forming a bond with the sulfonyl group of formula (I), wherein the 4-12-membered saturated cyclic or bicyclic alkyl is substituted with at least one ionisable moiety NR3R3'; where at least one of R3 and R3' is not hydrogen, but a substituent selected from the group consisting of straight or branched C4-C18-alkyl, aryl-C1-C18-alkyl, heteroaryl-C2-C18-alkyl, C1-C18-alkyl substituted with a C3-C12-cycloalkyl or -bicyclo or -tricycloalkyl, and whereby the alkyl chain may contain 1-3 O or S atoms. These sulfonamide derivatives are efficient modulators of the JNK pathway, they are in particular efficient and selective inhibitors of JNK 2 and 3. |