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Small‐molecule AT2 receptor agonists
Author(s) -
Hallberg Mathias,
Sumners Colin,
Steckelings U. Muscha,
Hallberg Anders
Publication year - 2018
Publication title -
medicinal research reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.868
H-Index - 130
eISSN - 1098-1128
pISSN - 0198-6325
DOI - 10.1002/med.21449
Subject(s) - agonist , chemistry , methylene , in vivo , imidazole , partial agonist , stereochemistry , in vitro , pharmacology , receptor , scaffold , derivative (finance) , small molecule , combinatorial chemistry , biochemistry , medicine , biology , medicinal chemistry , microbiology and biotechnology , financial economics , biomedical engineering , economics
The discovery of the first selective, small‐molecule ATR receptor (AT2R) agonist compound 21 (C21) ( 8 ) that is now extensively studied in a large variety of in vitro and in vivo models is described. The sulfonylcarbamate derivative 8 , encompassing a phenylthiofen scaffold is the drug‐like agonist with the highest affinity for the AT2R reported to date ( K i = 0.4 nM). Structure‐activity relationships (SAR), regarding different biaryl scaffolds and functional groups attached to these scaffolds and with a particular focus on the impact of various para substituents displacing the methylene imidazole group of 8 , are discussed. Furthermore, the consequences of migration of the methylene imidazole group and presumed structural requirements for ligands that are aimed as AT2R agonists (e.g. 8 ) or AT2R antagonists (e.g. 9 ), respectively, are briefly addressed. A summary of the pharmacological actions of C21 ( 8 ) is also presented.