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Bioorg Med Chem. 2013 Sep 15;21(18):5907-22. doi: 10.1016/j.bmc.2013.06.057. Epub 2013 Jul 2.

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.

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  • 1New Modality Research Laboratories, Daiichi Sankyo Co., Ltd, Shinagawa-ku, Tokyo, Japan. mori.yutaka.c7@daiichisankyo.co.jp


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 P1', P2' and P3 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 inhibition. Compound 32o exhibited a significant blood pressure lowering effect by oral administration in two hypertensive animal models, double transgenic rats and furosemide pretreated cynomolgus monkeys.

Copyright © 2013 Elsevier Ltd. All rights reserved.


Hypertension; Ketopiperazine; Piperidine; Renin

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