New nicotinic acid-based 3,5-diphenylpyrazoles: design, synthesis and antihyperlipidemic activity with potential NPC1L1 inhibitory activity

Article abstract of DOI:10.1007/s11030-020-10039-9

Nicotinic acid hydrazide was incorporated into new 4,5-dihydro-5-hydroxy-3,5-diphenylpyrazol-1-yl derivatives. Compounds 6a–h were synthesized, and their antihyperlipidemic activity was evaluated in high cholesterol diet-fed rat model. Compounds 6e, 6f were found to decrease the levels of serum total cholesterol by 14–19% compared to control group. Total triglycerides were also reduced by 24–28% and LDL cholesterol by 16%. As expected from parent niacin, compounds 6e and 6f caused an elevation of HDL cholesterol by 33–41%. Docking study supported the ability of designed compounds to block NPC1L1 active site in a manner similar to that observed with ezetimibe.