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

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.

Automated summary

The new synthesized compounds showed significant effects on reducing cholesterol and triglyceride levels in rats, while also increasing HDL cholesterol levels. Similar to ezetimibe, these compounds achieve their effects by blocking the NPC1L1 active site.