Synthesis and optimization of novel (3S, 5R)-5-(2, 2-dimethyl-5-oxo-4-phenylpiperazin-1-yl) piperidine-3-carboxamides as orally active renin inhibitors

…, A Mochizuki, Y Nakamura, T Fujimoto, C Sugita…

Index: Mori, Yutaka; Ogawa, Yasuyuki; Mochizuki, Akiyoshi; Nakamura, Yuji; Fujimoto, Teppei; Sugita, Chie; Miyazaki, Shojiro; Tamaki, Kazuhiko; Nagayama, Takahiro; Nagai, Yoko; Inoue, Shin-Ichi; Chiba, Katsuyoshi; Nishi, Takahide Bioorganic and Medicinal Chemistry, 2013 , vol. 21, # 18 p. 5907 - 5922

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Citation Number: 5

Abstract

Abstract We report synthesis and optimization of a series of (3S, 5R)-5-(2, 2-dimethyl-5-oxo- 4-phenylpiperazin-1-yl) piperidine-3-carboxamides as renin inhibitors. Chemical modification of P 1′ P 1′, P 2′ P 2′ and P 3 portions led to a promising 3, 5- disubstituted piperidine 32o showing high renin inhibitory activity and favorable oral exposure in both rats and cynomolgus monkeys with acceptable CYP and hERG current ...