Thiazole as a carbonyl bioisostere. A novel class of highly potent and selective 5-HT3 receptor antagonists.

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Rosen T, Nagel AA, Rizzi JP, Ives JL, Daffeh JB, Ganong AH, Guarino K, Heym J, McLean S, Nowakowski JT, et al.

Thiazole as a carbonyl bioisostere. A novel class of highly potent and selective 5-HT3 receptor antagonists.

J Med Chem. 1990 Oct;33(10):2715-20.

PubMed ID

2213824 [ View in PubMed

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Abstract

A novel structural class of highly potent and selective 5-HT3 receptor antagonists is described. The compounds in this new series contain a thiazole moiety linking an aromatic group and a nitrogen-containing basic region; the thiazole group appears to be acting as a carbonyl bioisostere in this system. An optimized member of this series, 4-(2-methoxyphenyl)-2-[[4(5)-methyl-5(4)-imidazolyl]methyl]thiazole (5), exhibits oral activity in the Bezold-Jarisch reflex paradigm comparable to or better than the standard agents ondansetron (1) and ICS-205-930 (2). Several of the structure-activity relationships are rationalized in terms of a computer pharmacophore model for 5-HT3 receptor binding.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Ondansetron	5-hydroxytryptamine receptor 3A	Ki (nM)	16	N/A	N/A	Details