STRUCTURAL-ANALYSIS OF 5-HT(3) RECEPTOR ANTAGONISTS - SYNTHESIS AND PHARMACOLOGICAL ACTIVITY OF VARIOUS AROMATIC ESTERS OR AMIDES DERIVED FROM TROPANE AND 1,2,6-TRISUBSTITUTED PIPERIDINE

被引：23

作者：

LANGLOIS, M ^{[1
]}

SOULIER, JL ^{[1
]}

YANG, D ^{[1
]}

BREMONT, B ^{[1
]}

FLORAC, C ^{[1
]}

RAMPILLON, V ^{[1
]}

GIUDICE, A ^{[1
]}

机构：

[1] SANOFI, CTR RECH, I-20137 MILAN, ITALY

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 28卷 / 11期

关键词：

SEROTONIN; 5-HT3; ANTAGONISTS; SAR; 1,2,6-TRISUBSTITUTED PIPERIDINES;

D O I：

10.1016/0223-5234(93)90039-H

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Preliminary results of a structure-activity relationship in the field of 5-HT3 receptor antagonists on the influence of the aromatic ring and steric hindrance around the basic nitrogen atom are reported. The favorable role of the naphthalene moiety substituted by a carbonyl function in position 1 was demonstrated by measuring the biological activity using the inhibition of the specific binding of [H-3]BRL 43694 and the inhibition of the Bezold-Jarisch reflex. Several esters and amides of 1,2,6-trisubstituted piperidine derivatives with a suitable fit with the antagonist reference compounds were synthesized. The lack of biological activity of these compounds emphasizes the importance of steric hindrance for binding with the anionic receptor site. These data confirm the major role of the tropane and quinuclidine frameworks in the potency of a number of 5-HT3 antagonists.

引用

页码：869 / 880

页数：12

共 43 条

[1] 5-HT3 ANTAGONISTS AND LIGANDS FOR DOPAMINE D1-RECEPTOR AND AUTORECEPTORS OFFER NEW LEADS FOR ANTIPSYCHOTIC-DRUGS [J].