Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, 61519, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sohag University, Sohâg, 82524, Egypt.
Mol Divers. 2021 May;25(2):673-686. doi: 10.1007/s11030-020-10039-9. Epub 2020 Feb 17.
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.
烟酰胺肼被引入到新的 4,5-二氢-5-羟基-3,5-二苯基吡唑-1-基衍生物中。合成了化合物 6a-h，并在高胆固醇饮食喂养的大鼠模型中评估了它们的抗高血脂活性。与对照组相比，化合物 6e 和 6f 可使血清总胆固醇水平降低 14-19%。总甘油三酯也降低了 24-28%，LDL 胆固醇降低了 16%。与烟酸母体一样，化合物 6e 和 6f 可使 HDL 胆固醇升高 33-41%。对接研究支持设计的化合物能够以类似于依折麦布观察到的方式阻断 NPC1L1 活性部位的能力。
