吡咯N-苄基化对选择性κ-阿片受体拮抗剂诺布啡宁的主要影响。

Major effect of pyrrolic N-benzylation in norbinaltorphimine, the selective kappa-opioid receptor antagonist.

作者信息

Chauvignac Cédric, Miller Carl N, Srivastava Sanjay K, Lewis John W, Husbands Stephen M, Traynor John R

机构信息

Department of Pharmacy and Pharmacology, University of Bath, Bath BA2 7AY, UK.

出版信息

J Med Chem. 2005 Mar 10;48(5):1676-9. doi: 10.1021/jm049172n.

DOI:10.1021/jm049172n

PMID:15743210

Abstract

Indolic N-benzylation of naltrindole reportedly extends the duration of delta-opioid receptor (DOR) antagonism. Similar modification of the kappa-opioid receptor (KOR) antagonist norBNI (1a) and its 17,17'-diNMe analogue (1d), a low potency mu-opioid receptor (MOR) partial agonist, was found to affect predominantly their MOR activity. When administered systemically in mouse antinociceptive assays, N-benzyl-norBNI (1b) had only MOR agonist activity of relatively short duration whereas on central administration it had only a KOR-antagonist action of extremely long duration.

摘要

据报道，纳曲吲哚的吲哚N-苄基化延长了δ-阿片受体（DOR）拮抗作用的持续时间。κ-阿片受体（KOR）拮抗剂norBNI（1a）及其17,17'-二甲基类似物（1d，一种低效μ-阿片受体（MOR）部分激动剂）的类似修饰被发现主要影响它们的MOR活性。在小鼠抗伤害感受试验中全身给药时，N-苄基-norBNI（1b）仅具有持续时间相对较短的MOR激动剂活性，而中枢给药时它仅具有持续时间极长的KOR拮抗作用。