Mono- or Diphenylpyridazines Connected to N-(2,4-Difluorophenyl)-N'-heptylurea as Acyl-CoA:Cholesterol Acyltransferase Inhibitors

Mono- and diphenylpyridazine ureido derivs. I (R1 = Ph, R2 = Ph; R1 = H, R2 = Ph; R1 = Ph, R2 = H; X = S, SO, SO2, or NH), structurally related to DuP 128 (II), were synthesized and tested for their inhibitory activity against ACAT isolated from rat liver microsomes. Several compds. displayed ACAT inhibition in the micromolar range. The amino derivs. I (R1 = Ph, R2 = Ph; R1 = H, R2 = Ph; R1 = Ph, R2 = H; X = NH) were also tested against hACAT-1 and hACAT-2 isoforms. They retained the same trend shown in the previous assay. Modeling studies on representative terms were performed. Significant similarities between the geometrical features of the model DuP 128 and the most active pyridazine derivs. were obsd.