探索阿片受体与氮杂环烷氨基酸的相互作用。一种强效且选择性的孤啡肽受体1拮抗剂的合成。

Probing opioid receptor interactions with azacycloalkane amino acids. Synthesis of a potent and selective ORL1 antagonist.

作者信息

Halab Liliane, Becker Jérôme A J, Darula Zsuzsanna, Tourwé Dirk, Kieffer Brigitte L, Simonin Frédéric, Lubell William D

机构信息

Département de Chimie, Université de Montréal, C. P. 6128, Succursale Centre Ville, Montréal, Québec, Canada H3C 3J7.

出版信息

J Med Chem. 2002 Nov 21;45(24):5353-7. doi: 10.1021/jm020078l.

DOI:10.1021/jm020078l

PMID:12431062

Abstract

Azacycloalkane turn mimics 6-9 were used to explore the relationship between conformation and biological activity of peptide ligands to the opioid receptor-like (ORL1) receptor. Three azabicyclo[x.y.0]alkane amino acids and a 5-tBuPro type VI beta-turn mimic were introduced into peptides 10-13 by solid-phase synthesis on MBHA resin. Biological examination of peptides 10-13 showed two new antagonists (10 and 12) exhibiting increased selectivity for the ORL1 receptor.

摘要

氮杂环烷环翻转模拟物6 - 9被用于探究肽配体与阿片样受体（ORL1）的构象和生物活性之间的关系。通过在MBHA树脂上进行固相合成，将三种氮杂双环[x.y.0]烷氨基酸和一种5 - tBuPro VI型β - 转角模拟物引入到肽10 - 13中。对肽10 - 13的生物学检测显示，有两种新型拮抗剂（10和12）对ORL1受体表现出更高的选择性。