Rational design and synthesis of 4-substituted 2-pyridin-2-ylamides with inhibitory effects on SH2 domain-containing inositol 5′-phosphatase 2 (SHIP2)

…, K Sugimoto, Y Matsuya, T Sasaoka, N Toyooka

Index: Ichihara, Yoshinori; Fujimura, Ryohei; Tsuneki, Hiroshi; Wada, Tsutomu; Okamoto, Kentaro; Gouda, Hiroaki; Hirono, Shuichi; Sugimoto, Kenji; Matsuya, Yuji; Sasaoka, Toshiyasu; Toyooka, Naoki European Journal of Medicinal Chemistry, 2013 , vol. 62, p. 649 - 660

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Citation Number: 11

Abstract

Novel 4-substituted 2-pyridin-2-ylamides were developed using in-silico ligand-based drug design (LBDD) in an attempt to identify inhibitors of SH2-containing 5′-inositol phosphatase 2 (SHIP2), which is implicated in insulin-resistant type 2 diabetes. Among the compounds synthesized, N-[4-(4-chlorobenzyloxy) pyridin-2-yl]-2-(2, 6-difluorophenyl)- acetamide (CPDA, 4a) was identified as a potent SHIP2 inhibitor. CPDA was found to ...