Discovery of 2-substituted benzoxazole carboxamides as 5-HT3 receptor antagonists.

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Yang Z, Fairfax DJ, Maeng JH, Masih L, Usyatinsky A, Hassler C, Isaacson S, Fitzpatrick K, DeOrazio RJ, Chen J, Harding JP, Isherwood M, Dobritsa S, Christensen KL, Wierschke JD, Bliss BI, Peterson LH, Beer CM, Cioffi C, Lynch M, Rennells WM, Richards JJ, Rust T, Khmelnitsky YL, Cohen ML, Manning DD

Discovery of 2-substituted benzoxazole carboxamides as 5-HT3 receptor antagonists.

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6538-41. doi: 10.1016/j.bmcl.2010.09.038. Epub 2010 Sep 16.

PubMed ID
20889341 [ View in PubMed
]
Abstract

A new class of 2-substituted benzoxazole carboxamides are presented as potent functional 5-HT(3) receptor antagonists. The chemical series possesses nanomolar in vitro activity against human 5-HT(3)A receptors. A chemistry optimization program was conducted and identified 2-aminobenzoxazoles as orally active 5-HT(3) 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-HT(3) receptor function, especially diarrhea predominant irritable bowel syndrome (IBS-D).

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
Alosetron5-hydroxytryptamine receptor 3AKi (nM)0.5N/AN/ADetails
AlosetronCytochrome P450 3A4IC 50 (nM)600N/AN/ADetails
Ondansetron5-hydroxytryptamine receptor 3AKi (nM)3.4N/AN/ADetails
OndansetronCytochrome P450 3A4IC 50 (nM)11000N/AN/ADetails