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ID: ALA3596108

Journal: Bioorg Med Chem

Title: Exploring S1 plasticity and probing S1' subsite of mammalian aminopeptidase N/CD13 with highly potent and selective aminobenzosuberone inhibitors.

Authors: Revelant G, Al-Lakkis-Wehbe M, Schmitt M, Alavi S, Schmitt C, Roux L, Al-Masri M, Schifano-Faux N, Maiereanu C, Tarnus C, Albrecht S.

Abstract: In order to probe the S1 and S1' mammalian aminopeptidase N subsites, racemic 1- or 4-substituted 7-aminobenzocyclohepten-6-one derivatives were synthesized and evaluated for their ability to inhibit mammalian aminopeptidase N. We focused on improving the physicochemical and ADME properties of this series by targeting lipophilicity and LELP score. Some 4-heteroaryl substituted analogues displayed reduced lipophilicity and enhanced inhibition potency with Ki values in the nanomolar range.

CiteXplore: 25982416

DOI: 10.1016/j.bmc.2015.04.066