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ID: ALA5247646
Journal: J Med Chem
Title: Discovery of 2-Aminopyrimidines as Potent Agonists for the Bitter Taste Receptor TAS2R14.
Authors: Waterloo L, Hübner H, Fierro F, Pfeiffer T, Brox R, Löber S, Weikert D, Niv MY, Gmeiner P.
Abstract: The bitter taste receptor TAS2R14 is a G protein-coupled receptor that is found on the tongue as well as in the human airway smooth muscle and other extraoral tissues. Because its activation causes bronchodilatation, TAS2R14 is a potential target for the treatment of asthma or chronic obstructive pulmonary disease. Structural variations of flufenamic acid, a nonsteroidal anti-inflammatory drug, led us to 2-aminopyridines showing considerable efficacy and potency in an IP1accumulation assay. In combination with an exchange of the carboxylic moiety by a tetrazole unit, a set of promising new TAS2R14 agonists was developed. The most potent ligand 28.1 (EC50 = 72 nM) revealed a six-fold higher potency than flufenamic acid and a maximum efficacy of 129%. Besides its unprecedented TAS2R14 activation, 28.1 revealed marked selectivity over a panel of 24 non-bitter taste human G protein-coupled receptors.
CiteXplore: 36847646