Abstract
Identification and SAR study of novel series of β 3-AR agonists with benzoic acid are described. Conversion of ether linkage position of phenoxybenzoic acid derivative 2b led to compound 7b with moderate β 3-AR activity. Further modification in right, center and left parts of compound 7b was investigated to improve the β 3-AR potency and selectivity. Compounds 7g and 7k, with the bulky aliphatic-substituted group at 2-position of benzoic acid moiety, were identified as potent and selective β 3-AR agonists. In addition, in vivo efficacy of compounds 7g and 7k was exhibited on dog OAB model.
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