THIAZOLE AS A CARBONYL BIOISOSTERE - A NOVEL CLASS OF HIGHLY POTENT AND SELECTIVE 5-HT3 RECEPTOR ANTAGONISTS

被引：44

作者：

ROSEN, T ^{[1
]}

NAGEL, AA ^{[1
]}

RIZZI, JP ^{[1
]}

IVES, JL ^{[1
]}

DAFFEH, JB ^{[1
]}

GANONG, AH ^{[1
]}

GUARINO, K ^{[1
]}

HEYM, J ^{[1
]}

MCLEAN, S ^{[1
]}

NOWAKOWSKI, JT ^{[1
]}

SCHMIDT, AW ^{[1
]}

SEEGER, TF ^{[1
]}

SIOK, CJ ^{[1
]}

VINCENT, LA ^{[1
]}

机构：

[1] PFIZER INC,DEPT NEUROSCI,GROTON,CT 06340

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 10期

关键词：

D O I：

10.1021/jm00172a006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel structural class of highly potent and selective 5-HT3receptor 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-HT3receptor binding. © 1990, American Chemical Society. All rights reserved.

引用

页码：2715 / 2720

页数：6

共 20 条

[1]

BAGLEY JR, 1981, J HETEROCYCLIC CHEM, V19, P485

[2] 5-HT3 RECEPTORS MEDIATE INHIBITION OF ACETYLCHOLINE-RELEASE IN CORTICAL TISSUE [J].