纳曲酮和羟吗啡酮的7-螺茚满基衍生物作为δ阿片受体的选择性配体。

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

作者信息

Ohkawa S, DiGiacomo B, Larson D L, Takemori A E, Portoghese P S

机构信息

Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455, USA.

出版信息

J Med Chem. 1997 May 23;40(11):1720-5. doi: 10.1021/jm9700880.

DOI:10.1021/jm9700880

PMID:9171881

Abstract

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-Pen2,D-Pen5]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.

摘要

为了研究正交取向的“地址”对δ阿片受体的作用，合成了由纳曲酮和羟吗啡酮的螺茚满基（5-7）、苯并螺茚满基（8-10）和螺并萘基（11）衍生物组成的一系列化合物。所有配体在体外均表现出对δ受体的偏好。7-苯并螺茚满基衍生物8（BSINTX）是体外最具选择性的δ阿片受体拮抗剂。在小鼠中，BSINTX拮抗δ1选择性激动剂[D- Pen2，D- Pen5]脑啡肽，而不显著影响δ2、μ和κ激动剂的镇痛效力。本研究结果与有利于δ1活性的正交取向地址一致。