卡格列净的发现：一种强效和长效的二肽基肽酶-4 抑制剂，用于治疗 2 型糖尿病。
Discovery of carmegliptin: a potent and long-acting dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes.
机构信息
F Hoffmann-La Roche Ltd, Pharma Research, CH-4070 Basel, Switzerland.
出版信息
Bioorg Med Chem Lett. 2010 Feb 1;20(3):1109-13. doi: 10.1016/j.bmcl.2009.12.024. Epub 2009 Dec 6.
PMID:20031405
Abstract
Design, synthesis, and SAR are described for a class of DPP-IV inhibitors based on aminobenzo[a]quinolizines with non-aromatic substituents in the S1 specificity pocket. One representative thereof, carmegliptin (8p), was chosen for clinical development. Its X-ray structure in complex with the enzyme and early efficacy data in animal models of type 2 diabetes are also presented.
摘要
本文描述了一类基于氨基苯并[a]喹啉并的 DPP-IV 抑制剂的设计、合成和 SAR 研究，该抑制剂在 S1 特异性口袋中具有非芳族取代基。其中一个代表性化合物是 carmegliptin（8p），已被选择用于临床开发。本文还介绍了其与酶的 X 射线结构以及在 2 型糖尿病动物模型中的早期疗效数据。
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