发现有效、选择性和口服生物利用度的三芳基磺酰胺基 PTP1B 抑制剂。
Discovery of potent, selective and orally bioavailable triaryl-sulfonamide based PTP1B inhibitors.
机构信息
Zydus Research Centre, Sarkhej-Bavla, N.H. 8A Moraiya, Ahmedabad 382210, India; Department of Chemistry, Faculty of Science, M.S. University of Baroda, Vadodara 390002, India.
出版信息
Bioorg Med Chem Lett. 2012 Jan 15;22(2):1111-7. doi: 10.1016/j.bmcl.2011.11.122. Epub 2011 Dec 6.
A novel series of pTyr mimetics containing triaryl-sulfonamide derivatives (5a-r) are reported as potent and selective PTP1B inhibitors. Some of the test compounds (5o and 5p) showed excellent selectivity towards PTP1B over various PTPs, including TCPTP (in vitro). The lead compound 5o showed potent antidiabetic activity (in vivo), along with improved pharmacokinetic profile. These preliminary results confirm discovery of highly potent and selective PTP1B inhibitors for the treatment of T2DM.
报告了一系列新型的含三芳基磺酰胺衍生物的 pTyr 模拟物（5a-r），它们是有效的、选择性的 PTP1B 抑制剂。一些测试化合物（5o 和 5p）对 PTP1B 表现出优异的选择性，对各种 PTP （包括 TCPTP ）（体外）具有优异的选择性。先导化合物 5o 表现出有效的抗糖尿病活性（体内），同时改善了药代动力学特征。这些初步结果证实了用于治疗 T2DM 的高度有效和选择性的 PTP1B 抑制剂的发现。
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