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Indexed by:期刊论文

Date of Publication:2014-09-01

Journal:BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Included Journals:SCIE、PubMed、Scopus

Volume:24

Issue:17

Page Number:4125-4128

ISSN No.:0960-894X

Key Words:Thiadiazole amides; Cdc25B; PTP1B; Cancer; Type-2 diabetes and obesity

Abstract:A series of novel thiadiazole amide derivatives have been synthesized and evaluated for inhibitory activities against Cdc25B and PTP1B. Most of them showed inhibitory activities against Cdc25B (IC50 = 1.18-8.01 mu g/mL) and PTP1B (IC50 = 0.85-8.75 mu g/mL), respectively. Moreover, compounds 5b and 4l were most potent with IC50 values of 1.18 and 0.85 mu g/mL for Cdc25B and PTP1B, respectively, compared with reference drugs Na3VO4 (IC50 = 0.93 mu g/mL) and oleanolic acid (IC50 = 0.85 mu g/mL). The results of selectivity experiments showed that the target compounds were selective inhibitors against PTP1B and Cdc25B. Enzyme kinetic experiments demonstrated that compound 5k was a specific inhibitor with the typical characteristics of a mixed inhibitor. (C) 2014 Elsevier Ltd. All rights reserved.