N-aminocarbonyl or thiocarbonyl fused heterocyclic cpds. - useful for treating diseases of lipid metabolism

摘要

The use of urea derivs. of formula (I) for treating diseases of lipid metabolism is new (Y is R or the gp. Q. n1 and n2 are 3-9. l is 0 or 1. R is up to 20C aliphatic hydrocarbyl (linear, branched or cyclic opt. unsatd. opt. substd. by halo, hydroxy, alkoxy, alkoxycarbonyl or opt. substd. aryl). R1 is H or lower alkyl. R2 is lower alkyl. R3, R4 and R5 are each H, halo, hydroxy, cyano, alkyl, alkoxy, alkoxycarbonyl, alkylthio, alkylsulphonyl, alkylsulphinyl, alkylcarbonyl (all lower), or opt. substd. aryl or aryloxy. X is oxygen or sulphur. A is -CR'R"-, -CR'R"-CH2-, -CR'=CH- or -Z-CR'R". Z is O, N(R") or -S(O)m. R' and R" are each H or lower alkyl. R"' is lower alkyl. m is 0-2). Cpds. (I) are new when R1 and R2 are 1-2C alkyl; R3, R4 and R5 are each H, chloro bromo-triflyoromethyl, alkyl, alkylthio, or alkoxy (all 1-4C), phenoxy or chlorophenoxy; A is -CR'R"-, -CR'R"-CH2-, -O.CR'R"- or -S.CR'R"-, with R' and R" each H, methyl, or ethyl, X is oxygen and (a) R is 6-18C alkyl or alkenyl (linear, branched or cyclic) opt. substd. by chloro, fluoro, 1-4C alkoxy or phenyl, or (b) R is the gp. Q. Cpds. include N.n.dodecyl aminocarbonyl -2,2,4-trimethyl 1,2,3,4-tetrahydroquinoline. Some (I) are already known to have phytotoxic activity and some are used as antidotes for iron poisoning. They are now found to have a strongly inhibiting action on lipid absorption in humands and animals so can be used to treat hyperlipidaemia. The usual daily dose is 1-50 mg per kg.