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Updated: Feb 16, 2026

A BW Reporter System for Studying Receptor-Ligand Interactions
Published on: January 7, 2019
A convenient transesterification method for synthesis of AT2 receptor ligands with improved stability in human liver
Johan Wannberg1, Rebecka Isaksson2, Ulf Bremberg1
1Department of Medicinal Chemistry, Science for Life Laboratory, BMC, Uppsala University, P.O. Box 574, SE-751 23 Uppsala, Sweden.
Abstract:
A series of AT2R ligands have been synthesized applying a quick, simple, and safe transesterification-type reaction whereby the sulfonyl carbamate alkyl tail of the selective AT2R antagonist C38 was varied. Furthermore, a limited number of compounds where acyl sulfonamides and sulfonyl ureas served as carboxylic acid bioisosteres were synthesized and evaluated. By reducing the size of the alkyl chain of the sulfonyl carbamates, ligands 7a and 7b were identified with significantly improved in vitro metabolic stability in both human and mouse liver microsomes as compared to C38 while retaining the AT2R binding affinity and AT2R/AT1R selectivity. Eight of the compounds synthesized exhibit an improved stability in human microsomes as compared to C38.
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