Novel renin inhibitors containing (2S,3S,5S)-2-amino-1-cyclohexyl-6- methyl-3,5-heptanediol fragment as a transition-state mimic at the P1-P1' cleavage site

Article abstract of DOI:10.1248/cpb.45.1631

A series of renin inhibitors containing the (2S,3S,5S)-2-amino-1- cyclohexyl-6-methyl-3,5-heptanediol (2-amino-3,5-anti-diol) fragment as a novel transition-state mimic was synthesized, and their biological activities were evaluated. All of the synthesized compounds containing the 2-amino-3,5- anti-diol fragment at the P1-P1' position showed high in vitro renin- inhibitory activity with IC₅₀ values in the 10^-8-10^-10 M range, and most of them caused a reduction of blood pressure when administered orally to salt-depleted, conscious marmosets. The inhibitor (29) with the 4- hydroxypiperidine residue at the P4 position showed the highest activity in terms of both potency and duration of the blood pressure-lowering effect.

Full text of DOI:10.1248/cpb.45.1631

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