Exploring S1 plasticity and probing S1′ subsite of mammalian aminopeptidase N/CD13 with highly potent and selective aminobenzosuberone inhibitors

被引：14
作者：
Revelant, Germain [1 ]
Al-Lakkis-Wehbe, Mira [1 ]
Schmitt, Marjorie [2 ]
Alavi, Sarah [1 ]
Schmitt, Celine [1 ]
Roux, Lionel [1 ]
Al-Masri, Mounir [1 ]
Schifano-Faux, Nadege [1 ]
Maiereanu, Carmen [1 ]
Tarnus, Celine [1 ]
Albrecht, Sebastien [1 ]
机构：
[1] Univ Haute Alsace, Lab Chim Organ & Bioorgan, EA4566, F-68093 Mulhouse, France
[2] Univ Strasbourg, Lab Chim Mol, CNRS UMR7509, F-67037 Strasbourg 2, France
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2015年 / 23卷 / 13期
关键词：
Cancer; Aminopeptidase N inhibitors; Racemic 1-or 4-substituted aminobenzocycloheptenone derivatives; Suzuki reaction; N APN/CD13; ANGIOGENESIS; CHEMISTRY; CD13/APN; TARGET; CELLS;
D O I：
10.1016/j.bmc.2015.04.066
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
In order to probe the S1 and S10 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 K-i values in the nanomolar range. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：3192 / 3207
页数：16
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