NOVEL GLUTAMIC-ACID DERIVED CHOLECYSTOKININ RECEPTOR LIGANDS

被引:21
作者
FREIDINGER, RM
WHITTER, WL
GOULD, NP
HOLLOWAY, MK
CHANG, RSL
LOTTI, VJ
机构
[1] Merck Sharp & Dohme Research Laboratories, West Point
关键词
D O I
10.1021/jm00164a020
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Novel aryl amide analogues of glutamic acid dialkylamide have been synthesized to test for a possible structural analogy between glutamic acid and benzodiazepine CCK antagonists such as compounds 2 and 24 (lorglumide and MK-329, respectively). In support of the structural model, certain of these hybrid compounds are more potent in pancreas CCK radioligand binding assays than corresponding lorglumide-type reference compounds. Modifications previously found in the benzodiazepine antagonists to result in brain CCK/gastrin receptor selectivity were also incorporated to produce an aryl urea series of glutamic acid analogues. None of these compounds were brain CCK/gastrin selective; however, one was potent and selective in the pancreas binding assay. The model appears to be most useful in the design of selective ligands for the pancreas type CCK receptor. © 1990, American Chemical Society. All rights reserved.
引用
收藏
页码:591 / 595
页数:5
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