title: N-Aryl Isoleucine Derivatives as Angiotensin II AT2 Receptor Ligands.
abstract: A novel series of ligands for the recombinant human AT2 receptor has been synthesized utilizing a fast and efficient palladium-catalyzed procedure for aminocarbonylation as the key reaction. Molybdenum hexacarbonyl [Mo(CO)6] was employed as the carbon monoxide source, and controlled microwave heating was applied. The prepared N-aryl isoleucine derivatives, encompassing a variety of amide groups attached to the aromatic system, exhibit binding affinities at best with K i values in the low micromolar range versus the recombinant human AT2 receptor. Some of the new nonpeptidic isoleucine derivatives may serve as starting points for further structural optimization. The presented data emphasize the importance of using human receptors in drug discovery programs.
authors.affiliation: Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University P.O. Box 574, SE-751 23 Uppsala (Sweden).
authors.forename: Malte
authors.initials: M
authors.lastname: Behrends
authors.affiliation: Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University P.O. Box 574, SE-751 23 Uppsala (Sweden).
authors.forename: Charlotta
authors.initials: C
authors.lastname: Wallinder
authors.affiliation: Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University P.O. Box 574, SE-751 23 Uppsala (Sweden).
authors.forename: Anna
authors.initials: A
authors.lastname: Wieckowska
authors.affiliation: Service of Endocrinology and Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke Sherbrooke, QC J1H 5N4 (Canada).
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Guimond
authors.affiliation: Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University P.O. Box 574, SE-751 23 Uppsala (Sweden).
authors.forename: Anders
authors.initials: A
authors.lastname: Hallberg
authors.affiliation: Service of Endocrinology and Department of Physiology and Biophysics, Faculty of Medicine, University of Sherbrooke Sherbrooke, QC J1H 5N4 (Canada).
authors.forename: Nicole
authors.initials: N
authors.lastname: Gallo-Payet
authors.affiliation: Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University P.O. Box 574, SE-751 23 Uppsala (Sweden).
authors.forename: Mats
authors.initials: M
authors.lastname: Larhed
keywords: AT2 receptor; aminocarbonylation; medicinal chemistry; palladium catalysis; peptide mimics