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PHENOLIC DERIVATIVES OF 1,2-METHANO-N,N-DIPROPYL-1,2,3,4-TETRAHYDRONAPHTH-2-YLAMINE - STRUCTURAL HYBRIDS OF 2-AMINOTETRALIN-DERIVED AND PHENYLCYCLOPROPYLAMINE-DERIVED 5-HT(1A)-RECEPTOR AGONISTS

被引：3
作者：
VALLGARDA, J
ARVIDSSON, LE
SVENSSON, BE
FOWLER, CJ
HACKSELL, U
机构：
[1] UNIV UPPSALA,CTR BIOMED,DEPT ORGAN PHARMACEUT CHEM,BOX 574,S-75123 UPPSALA,SWEDEN
[2] ASTRA ARCUS AB,CNS,PRECLIN RES & DEV,S-15185 SODERTALJE,SWEDEN
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 28卷 / 05期
关键词：
5-HT(1A)-RECEPTOR AGONISTS; 3-D MODELING; CYCLOPROPANATION;
D O I：
10.1016/0223-5234(93)90126-Y
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Three phenolic derivatives of 1,2-methano-N,N-dipropyl- 1,2,3,4-tetrahydronaphth-2-ylamine 6-8 were synthesized as structural hybrids of the potent 5-HT1A-receptor agonist 8-OH-DPAT 1 and 2 related phenolic phenylcyclopropylamines 4 and 5. The new compounds were assayed for 5-HT1A-receptor affinity and efficacy in vitro. Hybrids 6 and 7 were considered to be inactive but 8 had a K(i) value of 130 nM for [H-3]-8-OH-DPAT labelled 5-HT1A-receptors and produced an inhibition of the cAMP-production in the VIP-stimulated adenylyl cyclase assay. Thus, 8 is able to bind to and stimulate 5-HT1A-receptors. The results are discussed in relation to a previously described 3-D model for 5-HT1A-receptor agonists.
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收藏
页码：399 / 406
页数：8
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