A-RING ORTHO-DISUBSTITUTED APORPHINE DERIVATIVES AS POTENTIAL AGONISTS OR ANTAGONISTS AT SEROTONERGIC 5-HT1A RECEPTORS

被引：16

作者：

CANNON, JG ^{[1
]}

FLAHERTY, PT ^{[1
]}

OZKUTLU, U ^{[1
]}

LONG, JP ^{[1
]}

机构：

[1] UNIV IOWA,COLL MED,DEPT PHARMACOL,IOWA CITY,IA 52246

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 11期

关键词：

D O I：

10.1021/jm00011a002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

(R)- And (S)-11-hydroxy-10-methylaporphine 1 and 2 are, respectively, a potent, highly specific serotonergic (5-HT1A) agonist and antagonist. In an ongoing structure-activity study, racemates of the positional isomers 8-hydroxy-9-methyl- and 8-methyl-9-hydroxyaporphine were prepared by modifications of literature methods and were resolved. The methyl ethers of the target compounds were also evaluated pharmacologically. All of the free phenolic derivatives [(+)- and (-)-8 and 10] were inert in an assay for 5-HT1A receptor activity. All of the methyl ethers [(+)- and (-)-9 and 11] demonstrated quantitatively similar low potency stimulant effect at 5-HT1A receptors. The agonist or antagonist activity exhibited by 1 and 2 reflects the high degree of structural specificity required of aporphine derivatives for action at 5-HT1A receptors.

引用

页码：1841 / 1845

页数：5

共 14 条

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