Open AccessN ‐Aryl Isoleucine Derivatives as Angiotensin II AT 2 Receptor Ligands
Author(s) -
Behrends Malte,
Wallinder Charlotta,
Wieckowska Anna,
Guimond Marie-Odile,
Hallberg Anders,
Gallo-Payet Nicole,
Larhed Mats
Publication year - 2014
Publication title -
chemistryopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.644
H-Index - 29
ISSN - 2191-1363
DOI - 10.1002/open.201300040
Subject(s) - chemistry , aryl , isoleucine , amide , combinatorial chemistry , palladium , stereochemistry , carbon monoxide , organic chemistry , catalysis , amino acid , biochemistry , alkyl , leucine
A novel series of ligands for the recombinant human AT 2 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 AT 2 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.