DESIGN OF A POTENT 5-HT4 RECEPTOR AGONIST WITH NANOMOLAR AFFINITY

被引：32

作者：

LANGLOIS, M ^{[1
]}

ZHANG, L ^{[1
]}

YANG, D ^{[1
]}

BREMONT, B ^{[1
]}

SHEN, S ^{[1
]}

MANARA, L ^{[1
]}

CROCI, T ^{[1
]}

机构：

[1] SANOFI,I-20137 MILAN,ITALY

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1994年 / 4卷 / 12期

关键词：

D O I：

10.1016/S0960-894X(01)80508-4

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

It was demonstrated that potent and selective ligands for the 5-HT4 receptor devoid of 5-HT3 receptor antagonist properties could be designed from the esters of 4-amino-5-chloro-2-methoxybenzoic acid and the conformationally flexible piperidine framework derived from the locked structure of the quinuclidine ring of zacopride. The compounds were evaluated in binding essays with [H-3]-GR-113808 and [H-3]-BRL-43694 and fonctionally using electrically-evoked contractions in the guinea-pig ileum. Compound 7 exhibited nanomolar 5-HT4 receptor agonist activity.

引用

页码：1433 / 1436

页数：4

共 22 条

[1] BOCKAERT J, 1991, SEROTONIN : MOLECULAR BIOLOGY, RECEPTORS AND FUNCTIONAL EFFECTS, P220
[2] BUCHHEIT KH, 1992, N-S ARCH PHARMACOL, V345, P387
[3] CLARKE DE, 1991, SEROTONIN : MOLECULAR BIOLOGY, RECEPTORS AND FUNCTIONAL EFFECTS, P232
[4] COHEN ML, 1990, J PHARMACOL EXP THER, V254, P350
[5] CRAIG D A, 1989, British Journal of Pharmacology, V96, p247P
[6] DUMUIS A, 1988, MOL PHARMACOL, V34, P880
[7] RS-23597-190 - A POTENT AND SELECTIVE 5-HT4 RECEPTOR ANTAGONIST
EGLEN, RM
BLEY, K
BONHAUS, DW
CLARK, RD
HEGDE, SS
JOHNSON, LG
LEUNG, E
WONG, EHF
[J]. BRITISH JOURNAL OF PHARMACOLOGY, 1993, 110 (01) : 119 - 126
[8] THE ACTION OF SDZ 205,557 AT 5-HYDROXYTRYPTAMINE (5-HT3 AND 5-HT4) RECEPTORS
EGLEN, RM
ALVAREZ, R
JOHNSON, LG
LEUNG, E
WONG, EHF
[J]. BRITISH JOURNAL OF PHARMACOLOGY, 1993, 108 (02) : 376 - 382
[9] IDENTIFICATION OF PUTATIVE 5-HT4-RECEPTORS IN GUINEA-PIG ASCENDING COLON
ELSWOOD, CJ
BUNCE, KT
HUMPHREY, PPA
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 1991, 196 (02) : 149 - 155
[10] FLYNN DL, 1992, J MED CHEM, V35, P1489

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