Thiazole as a Carbonyl Bioisostere. A Novel Class of Highly Potent and Selective 5-HT3 Receptor Antagonists
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-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.
Rosen, Terry,Nagel, Arthur A.,Rizzi, James P.,Ives, Jeffrey L.,Daffeh, June B.,et al.
p. 2715 - 2720
(2007/10/02)
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