title: Exploring S1 plasticity and probing S1' subsite of mammalian aminopeptidase N/CD13 with highly potent and selective aminobenzosuberone inhibitors.
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.
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique, EA4566, Université de Haute Alsace, F-68093 Mulhouse Cedex, France.
authors.forename: Germain
authors.initials: G
authors.lastname: Revelant
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique, EA4566, Université de Haute Alsace, F-68093 Mulhouse Cedex, France.
authors.forename: Mira
authors.initials: M
authors.lastname: Al-Lakkis-Wehbe
authors.affiliation: Laboratoire de Chimie Moléculaire, CNRS-UMR7509, Université de Strasbourg, F-67037 Strasbourg Cedex2, France.
authors.forename: Marjorie
authors.initials: M
authors.lastname: Schmitt
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique, EA4566, Université de Haute Alsace, F-68093 Mulhouse Cedex, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Alavi
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique, EA4566, Université de Haute Alsace, F-68093 Mulhouse Cedex, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Schmitt
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique, EA4566, Université de Haute Alsace, F-68093 Mulhouse Cedex, France.
authors.forename: Lionel
authors.initials: L
authors.lastname: Roux
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique, EA4566, Université de Haute Alsace, F-68093 Mulhouse Cedex, France.
authors.forename: Mounir
authors.initials: M
authors.lastname: Al-Masri
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique, EA4566, Université de Haute Alsace, F-68093 Mulhouse Cedex, France.
authors.forename: Nadège
authors.initials: N
authors.lastname: Schifano-Faux
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique, EA4566, Université de Haute Alsace, F-68093 Mulhouse Cedex, France.
authors.forename: Carmen
authors.initials: C
authors.lastname: Maiereanu
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique, EA4566, Université de Haute Alsace, F-68093 Mulhouse Cedex, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Tarnus
authors.affiliation: Laboratoire de Chimie Organique et Bioorganique, EA4566, Université de Haute Alsace, F-68093 Mulhouse Cedex, France. Electronic address: sebastien.albrecht@uha.fr.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Albrecht
mesh_terms: D062365:Aminobenzoates / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D001567:Benzocycloheptenes / Q000138:chemical synthesis* / Q000737:chemistry; D018826:CD13 Antigens / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000302:isolation & purification; D007668:Kidney / Q000737:chemistry / Q000201:enzymology; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013552:Swine; D013816:Thermodynamics
chemical_list: D062365:Aminobenzoates; D001567:Benzocycloheptenes; D011480:Protease Inhibitors; D018826:CD13 Antigens
keywords: Aminopeptidase N inhibitors; Cancer; Racemic 1- or 4-substituted aminobenzocycloheptenone derivatives; Suzuki reaction