Aminopyrazole–Phenylalanine Based GPR142 Agonists: Discovery of Tool Compound and in Vivo Efficacy Studies

…, M Murakoshi, F Nara, K Oda, R Okuyama…

Index: Yu, Ming; Lizarzaburu, Mike; Motani, Alykhan; Fu, Zice; Du, Xiaohui; Liu, Jiwen; Jiao, Xianyun; Lai, Sujen; Fan, Peter; Fu, Angela; Liu, Qingxiang; Murakoshi, Michiko; Nara, Futoshi; Oda, Kozo; Okuyama, Ryo; Reagan, Jeff D.; Watanabe, Nobuaki; Yamazaki, Mami; Xiong, Yumei; Zhang, Ying; Zhuang, Run; Lin, Daniel C.-H.; Houze, Jonathan B.; Medina, Julio C.; Li, Leping ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 9 p. 829 - 834

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Citation Number: 6

Abstract

Herein, we report the lead optimization of amrinone–phenylalanine based GPR142 agonists. Structure–activity relationship studies led to the discovery of aminopyrazole– phenylalanine carboxylic acid 22, which exhibited good agonistic activity, high target selectivity, desirable pharmacokinetic properties, and no cytochrome P450 or hERG liability. Compound 22, together with its orally bioavailable ethyl ester prodrug 23, were found to ...