Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Feb 1;28(3):519-522.
doi: 10.1016/j.bmcl.2017.11.042. Epub 2017 Nov 24.

A convenient transesterification method for synthesis of AT2 receptor ligands with improved stability in human liver microsomes

Johan Wannberg  1 , Rebecka Isaksson  2 , Ulf Bremberg  1 , Maria Backlund  3 , Jonas Sävmarker  4 , Mathias Hallberg  5 , Mats Larhed  6
Affiliations

A convenient transesterification method for synthesis of AT2 receptor ligands with improved stability in human liver microsomes

Johan Wannberg et al. Bioorg Med Chem Lett. .

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.

Keywords: AT(2)R antagonists; Angiotensin II type 2 receptor antagonists; Liver microsomes; Sulfonyl carbamates; Transesterification.

PubMed Disclaimer

Publication types

LinkOut - more resources