Gupta Ramesh C, Chhipa Laxmikant, Mandhare Appaji B, Zambad Shitalkumar P, Chauthaiwale Vijay, Nadkarni Sunil S, Dutt Chaitanya
Medicinal Chemistry, Torrent Research Centre, Torrent Pharmaceuticals Ltd., Gandhinagar, Gujarat, India.
Bioorg Med Chem Lett. 2009 Sep 1;19(17):5021-5. doi: 10.1016/j.bmcl.2009.07.058. Epub 2009 Jul 12.
A novel class of N-substituted 4-hydrazino piperidine derivatives were designed, synthesized and evaluated for DPP IV inhibition. The SAR studies on the N-substituted piperidine led to the discovery of compound 22e as a potent DPP IV inhibitor (IC(50) 88nM), which is highly selective over other peptidases. In vivo efficacy indicates that compound 22e stimulates insulin release in response to glucose load and improves glucose tolerance in n5-STZ and Zucker Diabetic Fatty (ZDF) rats.
设计、合成并评估了一类新型的N-取代4-肼基哌啶衍生物对二肽基肽酶IV（DPP IV）的抑制作用。对N-取代哌啶的构效关系研究发现化合物22e是一种有效的DPP IV抑制剂（IC(50) 88 nM），对其他肽酶具有高度选择性。体内药效学研究表明，化合物22e能响应葡萄糖负荷刺激胰岛素释放，并改善链脲佐菌素诱导的糖尿病（n5-STZ）大鼠和Zucker糖尿病脂肪大鼠（ZDF）的糖耐量。
