7-spiroindanyl derivatives of naltrexone and oxymorphone as selective ligands for delta opioid receptors

被引：20

作者：

Ohkawa, S

DiGiacomo, B

Larson, DL

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 | 1997年 / 40卷 / 11期

关键词：

D O I：

10.1021/jm9700880

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series consisting of spiroindanyl (5-7), benzospiroindanyl (8-10), and spiroperinaphthyl (11) derivatives of naltrexone and oxymorphone were synthesized in order to investigate the role of an orthogonal-oriented ''address'' for delta opioid receptors. All of the ligands exhibited a preference for delta receptors in vitro. The 7-benzospiroindanyl derivative 8 (BSINTX) was the most selective delta opioid receptor antagonist in vitro. In mice BSINTX antagonized the delta(1)-selective agonist, [D-Pen(2),D-Pen(5)]enkephalin without significantly affecting the antinociceptive potency of delta(2), mu, and kappa agonists. The results of this study are consistent with an orthogonally-oriented address favoring delta(1) activity.

引用

页码：1720 / 1725

页数：6