Discovery and Development of S6821 and S7958 as Potent TAS2R8 Antagonists
Autor: | Lan Zhang, Hanghui Liu, Brett Weylan Ching, Guy Servant, Tanya Ditschun, Andrew Patron, Thomas Brady, Mark C. Williams, Melissa Arellano, Vincent Darmohusodo, Michael Saganich, Qing Chen, Timothy Davis, Catherine Tachdjian, Donald S. Karanewsky, Joseph R. Fotsing |
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Rok vydání: | 2020 |
Předmět: |
Receptors
Cell Surface Pharmacology 01 natural sciences Coffee Receptors G-Protein-Coupled 03 medical and health sciences Structure-Activity Relationship Nutraceutical stomatognathic system Sensory tests Drug Stability Drug Discovery Animals Humans 030304 developmental biology Active ingredient 0303 health sciences Molecular Structure Drug discovery Chemistry Hydantoins food and beverages Bitter taste 0104 chemical sciences Rats 010404 medicinal & biomolecular chemistry Taste Molecular Medicine Pyrazoles |
Zdroj: | Journal of medicinal chemistry. 63(9) |
ISSN: | 1520-4804 |
Popis: | In humans, bitter taste is mediated by 25 TAS2Rs. Many compounds, including certain active pharmaceutical ingredients, excipients, and nutraceuticals, impart their bitter taste (or in part) through TAS2R8 activation. However, effective TAS2R8 blockers that can either suppress or reduce the bitterness of these compounds have not been described. We are hereby reporting a series of novel 3-(pyrazol-4-yl) imidazolidine-2,4-diones as potent and selective TAS2R8 antagonists. In human sensory tests, S6821 and S7958, two of the most potent analogues from the series, demonstrated efficacy in blocking TAS2R8-mediated bitterness and were selected for development. Following data evaluation by expert panels of a number of national and multinational regulatory bodies, including the US, the EU, and Japan, S6821 and S7958 were approved as safe under conditions of intended use as bitter taste blockers. |
Databáze: | OpenAIRE |
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