N-Aryl Isoleucine Derivatives as Angiotensin II AT2 Receptor Ligands
Article first published online: 13 MAR 2014
© 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Volume 3, Issue 2, pages 65–75, April 2014
How to Cite
Behrends, M., Wallinder, C., Wieckowska, A., Guimond, M.-O., Hallberg, A., Gallo-Payet, N. and Larhed, M. (2014), N-Aryl Isoleucine Derivatives as Angiotensin II AT2 Receptor Ligands. ChemistryOpen, 3: 65–75. doi: 10.1002/open.201300040
- Issue published online: 19 APR 2014
- Article first published online: 13 MAR 2014
- Manuscript Received: 18 NOV 2013
- Swedish Research Council
- Canadian Diabetes Association. Grant Number: OG-3–10–3021-NG
- Alzheimer Society of Canada. Grant Number: #1136
- AT2 receptor;
- medicinal chemistry;
- palladium catalysis;
- peptide mimics
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 Ki 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.