Discovery of 2-Aminopyrimidines as Potent Agonists for the Bitter Taste Receptor TAS2R14

Waterloo L, Hübner H, Fierro F, Pfeiffer T, Brox R, Löber S, Weikert D, Niv MY, Gmeiner P (2023)

Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 66

Pages Range: 3499-3521

Journal Issue: 5

DOI: 10.1021/acs.jmedchem.2c01997

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.

Authors with CRIS profile

Involved external institutions

Hebrew University of Jerusalem Israel (IL)

How to cite

APA:

Waterloo, L., Hübner, H., Fierro, F., Pfeiffer, T., Brox, R., Löber, S.,... Gmeiner, P. (2023). Discovery of 2-Aminopyrimidines as Potent Agonists for the Bitter Taste Receptor TAS2R14. Journal of Medicinal Chemistry, 66(5), 3499-3521. https://dx.doi.org/10.1021/acs.jmedchem.2c01997

MLA:

Waterloo, Lukas, et al. "Discovery of 2-Aminopyrimidines as Potent Agonists for the Bitter Taste Receptor TAS2R14." Journal of Medicinal Chemistry 66.5 (2023): 3499-3521.

BibTeX: Download