Antihyperlipidemic and anti-atherosclerotic trisubstituted urea compounds.

摘要

Compounds of the formula <CHEM> wherein A is each independently CH or N; R1, R2, and R3 are each independently hydrogen, alkyl of one to six carbon atoms, halogen or alkoxy of one to six carbon atoms; R4 is alkyl of four to ten carbon atoms, cycloalkyl of three to seven carbon atoms, benzyl or benzyl substituted by alkyl of one to six carbon atoms, alkoxy of one to six carbon atoms, halogen COOR min where R min is H, alkyl, NR min _1R min _2 where R min _1 and R min _2 are each independently hydrogen, alkyl or cycloalkyl of three to seven carbon atoms; and R5 is selected from the group of the formulae <CHEM> wherein n is zero, 1 or 2; n min is 2 to 6; n sec is zero or 1; Ar is phenyl, naphthyl, pyridyl, thienyl or furanyl, or phenyl, naphthyl, pyridyl, thienyl or furanyl substituted by alkyl of one to six carbon atoms, hydroxy, alkoxy of one to six carbon atoms, benzyloxy, fluorine, chlorine, bromine, nitro, trifluoromethyl, -NHCOCH3, -CONH2, -COOH, -COO-alkyl, -CH2COOH, -CH2CONH2 or NR min _1R min _2; X is -CH2, O, S, SO, or SO2; R6 and R7 are each independently alkyl of one to six carbon atoms, hydroxy, alkoxy of one to six carbon atoms, benzyloxy, halogen, nitro, trifluoromethyl, -COOH, -CONH2, -COO-alkyl, or NR min _1R min _2; with the proviso that when R5 is <CHEM> Ar cannot be naphthyl; or pharmaceutically acceptable acid addition or base salts thereof, useful as potent inhibitors of the enzyme acyl-CoA:cholesterol acyltransferase, their method of manufacture, pharmaceutical compositions containing such compounds as well as methods of inhibiting the interstitial absorption of cholesterol and lowering blood plasma cholesterol with such compounds are described.