Discovery of novel series of benzoic acid derivatives containing biphenyl ether moiety as potent and selective human beta(3)-adrenergic receptor agonists: Part IV.

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Nakajima Y, Imanishi M, Itou S, Hamashima H, Tomishima Y, Washizuka K, Sakurai M, Matsui S, Imamura E, Ueshima K, Yamamoto T, Yamamoto N, Ishikawa H, Nakano K, Unami N, Hamada K, Hattori K

Discovery of novel series of benzoic acid derivatives containing biphenyl ether moiety as potent and selective human beta(3)-adrenergic receptor agonists: Part IV.

Bioorg Med Chem Lett. 2008 Sep 15;18(18):5037-40. doi: 10.1016/j.bmcl.2008.08.009. Epub 2008 Aug 7.

PubMed ID
18752946 [ View in PubMed
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Abstract

Identification and SAR study of novel series of beta(3)-AR agonists with benzoic acid are described. Conversion of ether linkage position of phenoxybenzoic acid derivative 2b led to compound 7b with moderate beta(3)-AR activity. Further modification in right, center and left parts of compound 7b was investigated to improve the beta(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 beta(3)-AR agonists. In addition, in vivo efficacy of compounds 7g and 7k was exhibited on dog OAB model.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
IsoprenalineBeta-1 adrenergic receptorEC 50 (nM)0.084N/AN/ADetails
IsoprenalineBeta-3 adrenergic receptorEC 50 (nM)0.97N/AN/ADetails