title: Interconversion of Functional Activity by Minor Structural Alterations in Nonpeptide AT2 Receptor Ligands.
abstract: Migration of the methylene imidazole side chain in the first reported selective drug-like AT2 receptor agonist C21/M024 (1) delivered the AT2 receptor antagonist C38/M132 (2). We now report that the AT2 receptor antagonist compound 4, a biphenyl derivative that is structurally related to 2, is transformed to the agonist 6 by migration of the isobutyl group. The importance of the relative position of the methylene imidazole and the isobutyl substituent is highlighted herein.
authors.affiliation: Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, BMC, Uppsala University , SE-751 23 Uppsala, Sweden.
authors.forename: Charlotta
authors.initials: C
authors.lastname: Wallinder
authors.affiliation: Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, BMC, Uppsala University , SE-751 23 Uppsala, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Sköld
authors.affiliation: Beijer Laboratory, Department of Pharmaceutical Biosciences, BMC, Uppsala University SE-751 23 Uppsala, Sweden.
authors.forename: Milad
authors.initials: M
authors.lastname: Botros
authors.affiliation: Service of Endocrinology, Faculty of Medicine and Heath Sciences, University of Sherbrooke , Sherbrooke J1H 5N4, Quebec, Canada.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Guimond
authors.affiliation: Beijer Laboratory, Department of Pharmaceutical Biosciences, BMC, Uppsala University SE-751 23 Uppsala, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Hallberg
authors.affiliation: Service of Endocrinology, Faculty of Medicine and Heath Sciences, University of Sherbrooke , Sherbrooke J1H 5N4, Quebec, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Gallo-Payet
authors.affiliation: Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, BMC, Uppsala University , SE-751 23 Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Karlén
authors.affiliation: Organic Pharmaceutical Chemistry, Department of Medicinal Chemistry, BMC, Uppsala University , SE-751 23 Uppsala, Sweden.
authors.forename: Mathias
authors.initials: M
authors.lastname: Alterman
keywords: AT2 receptor; C21/M024; C38/M132; agonist; antagonist; nonpeptide ligands