Discovery of novel pyrimidine and malonamide derivatives as TGR5 agonists
Takeda G-protein-coupled receptor 5 (TGR5) is a promising molecular target for metabolic diseases. A series of 4-(2,5-dichlorophenoxy)pyrimidine and cyclopropylmalonamide derivatives were synthesized as potent agonists of TGR5 based on a bioisosteric replacement strategy. Several compounds exhibited...
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Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2014-09, Vol.24 (17), p.4271-4275 |
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Hauptverfasser: | , , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
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Online-Zugang: | Volltext |
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Zusammenfassung: | Takeda G-protein-coupled receptor 5 (TGR5) is a promising molecular target for metabolic diseases. A series of 4-(2,5-dichlorophenoxy)pyrimidine and cyclopropylmalonamide derivatives were synthesized as potent agonists of TGR5 based on a bioisosteric replacement strategy. Several compounds exhibited improved potency, compared to a reference compound with a pyridine scaffold. The pharmacokinetic profile of the representative compound 18 was considered moderate. |
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ISSN: | 0960-894X 1464-3405 |
DOI: | 10.1016/j.bmcl.2014.07.026 |