SYNTHESIS AND DELTA-OPIOID RECEPTOR ANTAGONIST ACTIVITY OF A NALTRINDOLE ANALOG WITH A REGIOISOMERIC INDOLE MOIETY

被引：8

作者：

PORTOGHESE, PS ^{[1
]}

OHKAWA, S ^{[1
]}

MOE, ST ^{[1
]}

TAKEMORI, AE ^{[1
]}

机构：

[1] UNIV MINNESOTA,SCH MED,DEPT PHARMACOL,MINNEAPOLIS,MN 55455

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1994年 / 37卷 / 12期

关键词：

D O I：

10.1021/jm00038a019

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Indolomorphinans 2 and 3, in which the indole moiety is fused to the 7,8-position of the morphinan system, have been synthesized from dihydropseudocodeinone 4 and evaluated for antagonist activity on the mouse vas deferens (MVD) and guinea pig ileum (GPI) preparations. Indolomorphinan 2 was found to be similar to 1/60th as potent as naltrindole 1 in the MVD and an agonist in the GPI preparation. A comparable difference in affinity between 1 and 2 was observed. The methyl analogue 3 was inactive in both preparations. The results of this study support the idea that the regio orientation of the indolic benzene moiety of 1 is optimal for delta-opioid receptor antagonist activity. It is proposed that the proper alignment of the benzene moiety with an address subsite on the delta receptor is critical for potent delta antagonist activity.

引用

页码：1886 / 1888

页数：3

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