N-取代八氢-4a-(3-羟基苯基)-10a-甲基苯并[g]异喹啉类是阿片受体纯拮抗剂。

N-substituted octahydro-4a-(3-hydroxyphenyl)-10a-methyl-benzo[g]isoquinolines are opioid receptor pure antagonists.

作者信息

Thomas J B, Mascarella S W, Burgess J P, Xu H, McCullough K B, Rothman R B, Flippen-Anderson J L, George C F, Cantrell B E, Zimmerman D M, Carroll F I

机构信息

Chemistry and Life Sciences, Research Triangle Institute, North Carolina 27709, USA.

出版信息

Bioorg Med Chem Lett. 1998 Nov 17;8(22):3149-52. doi: 10.1016/s0960-894x(98)00576-9.

DOI:10.1016/s0960-894x(98)00576-9

PMID:9873693

Abstract

N-Methyl- and N-phenylethyl-(+/-)-1,2,3,4,4a,5,10,10a- octahydro-4a-(3-hydroxyphenyl)-10a-methyl-benzo[g]isoquinolines (4 and 5, respectively) were found to be pure opioid antagonists. These compounds were shown to share many of the characteristics identified with the N-methyl- and N-phenylethyl trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine (1 and 2, respectively) including N-substituent mediated potency and a lack of N-substituent mediated antagonism. These data suggest that compounds 4 and 5 and the N-substituted trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidines (1 and 2) may interact with opioid receptors similarly.

摘要

已发现 N-甲基-和 N-苯乙基-(±)-1,2,3,4,4a,5,10,10a-八氢-4a-(3-羟基苯基)-10a-甲基苯并[g]异喹啉（分别为 4 和 5）是纯阿片样物质拮抗剂。这些化合物表现出与 N-甲基-和 N-苯乙基反式-3,4-二甲基-4-(3-羟基苯基)哌啶（分别为 1 和 2）相同的许多特性，包括 N-取代基介导的效力以及缺乏 N-取代基介导的拮抗作用。这些数据表明，化合物 4 和 5 与 N-取代的反式-3,4-二甲基-4-(3-羟基苯基)哌啶（1 和 2）可能以相似的方式与阿片样物质受体相互作用。