ORL1 receptor ligands:: Structure-activity relationships of 8-cycloalkyl-1-phenyl-1,3,8-triaza-spiro[4.5]decan-4-ones

被引：27
|
作者：
Röver, S [1 ]
Wichmann, J [1 ]
Jenck, F [1 ]
Adam, G [1 ]
Cesura, AM [1 ]
机构：
[1] F Hoffmann La Roche Ltd, PRBC, Div Pharma, CH-4070 Basel, Switzerland
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 08期
关键词：
D O I：
10.1016/S0960-894X(00)00111-6
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
We have investigated 5-cycloalkyl-1-phenyl-1,3,8-triaza-spirol4.5ldecan-4-ones as ligands for the ORL1 receptor. These unsophisticated, achiral compounds show remarkable affinity for the ORL1 receptor. Optimizing for selectivity we show that the maximum of affinity and selectivity versus the other opioid receptors is achieved for 8-cyclodecyl-1-phenyl-1,3,8-triaza-spiro-[4.5] decan-4-one 2e and 8-(cis-4-isopropyl-cyclohexyl)-1-phenyl- 1,3,8 -triaza-spiro[4.5]decan-4-one 2q. The identified compounds (2e, 2q) are more or less equipotent to the natural ligand itself, both in the binding assay and in the functional GTP gamma S assay. (C) 2000 Elsevier Science Ltd. All rights reserved.
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页码：831 / 834
页数：4
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