Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1371600 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
A new class of 2-substituted benzoxazole carboxamides are presented as potent functional 5-HT3 receptor antagonists. The chemical series possesses nanomolar in vitro activity against human 5-HT3A receptors. A chemistry optimization program was conducted and identified 2-aminobenzoxazoles as orally active 5-HT3 receptor antagonists with good metabolic stability. These novel analogues possess drug-like characteristics and have potential utility for the treatment of diseases attributable to improper 5-HT3 receptor function, especially diarrhea predominant irritable bowel syndrome (IBS-D).
Graphical abstractThe discovery of a novel series of benzoxazole-4-carboxamides is described. A structure–activity relationship study resulted in the identification of 2-amino benzoxazoles 41 and 48 as selective, orally bioavailable 5-HT3 receptor antagonists.Figure optionsDownload full-size imageDownload as PowerPoint slide