Ureidopyridazine derivatives as acyl-CoA:cholesterol acyltransferase inhibitors

Abstract

A series of N-(2,4-difluorophenyl)-N′-heptyl-N′-{4- [(substituted)-pyridazin-3-yl)thio]pentyl}urea derivatives having a phenyl ring at positions 5 and/or at position 6 of the heterocycle, as well as the corresponding sulfones, were synthesized. Their inhibitory activity against acyl-CoA:cholesterol acyltransferase (ACAT) was tested on the enzyme prepared from rat liver microsomes. Theoretical studies were performed to correlate their activity to their structural features.