School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi Nagar, Bhopal, MP 462036, India.
School of Pharmaceutical Sciences, Rajiv Gandhi Proudyogiki Vishwavidyalaya, Airport Bypass Road, Gandhi Nagar, Bhopal, MP 462036, India; Department of Pharmacy, Indira Gandhi National Tribal University, Lalpur, Amarkantak, MP 484887, India.
Bioorg Chem. 2019 Nov;92:103221. doi: 10.1016/j.bioorg.2019.103221. Epub 2019 Aug 30.
A series of ten N-(3-(1H-tetrazole-5-yl)phenyl)acetamide derivatives (NM-07 to NM-16) designed from a lead molecule identified previously in our laboratory were synthesized and evaluated for protein tyrosine phosphatase 1B (PTP1B) inhibitory activity. Among the synthesized molecules, NM-14, a 5-Cl substituted benzothiazole analogue elicited significant PTP1B inhibition with an IC of 1.88 µM against reference standard suramin (IC ≥ 10 µM). Furthermore, this molecule also showed good in vivo antidiabetic activity which was comparable to that of standard antidiabetic drugs metformin and glimepiride. Overall, the results of the study clearly reveal that the reported tetrazole derivatives especially NM-14 are valuable prototypes for the development of novel non-carboxylic inhibitors of PTP1B with antidiabetic potential.
我们实验室之前从一个先导分子出发设计了一系列十个 N-(3-(1H-四唑-5-基)苯基)乙酰胺衍生物（NM-07 到 NM-16），并对其进行了蛋白酪氨酸磷酸酶 1B（PTP1B）抑制活性评估。在所合成的分子中，NM-14，一种 5-Cl 取代的苯并噻唑类似物，对参考标准苏拉明（IC≥10µM）表现出显著的 PTP1B 抑制作用，IC 为 1.88µM。此外，该分子还表现出良好的体内抗糖尿病活性，与标准抗糖尿病药物二甲双胍和格列美脲相当。总的来说，研究结果清楚地表明，所报道的四唑衍生物，特别是 NM-14，是具有抗糖尿病潜力的新型非羧酸 PTP1B 抑制剂的有价值的原型。
