SYNTHESIS AND KAPPA-OPIOID ANTAGONIST SELECTIVITY OF A NORBINALTORPHIMINE CONGENER - IDENTIFICATION OF THE ADDRESS MOIETY REQUIRED FOR KAPPA-ANTAGONIST ACTIVITY

被引：35

作者：

LIN, CE

TAKEMORI, AE

PORTOGHESE, PS

机构：

[1] UNIV MINNESOTA,COLL PHARM,DEPT MED CHEM,MINNEAPOLIS,MN 55455

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 36卷 / 16期

关键词：

D O I：

10.1021/jm00068a020

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compound 2, which represents a structurally simplified congener of norbinaltorphimine 1a, was synthesized in order to evaluate the role of its second basic nitrogen-in conferring kappa-opioid receptor antagonist selectivity. Congener 2 was found to beat least twice as selective as 1a as a kappa antagonist, while its N-carbobenzoxy derivative (3) was inactive at kappa-receptors. This study establishes the importance of the second basic nitrogen of 1a for kappa-receptor recognition. It is proposed that this basic group.mimics the guanidinium moiety of Arg7, which may be the key kappa-address component of dynorphin.

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页码：2412 / 2415

页数：4

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