Synthesis and biological activity of N-methylated analogs of endomorphin-2

被引：30

作者：

Kruszynski, R

Fichna, J

Do-Rego, JC

Janecki, T

Kosson, P

Pakulska, W

Costentin, J

Janecka, A ^{[1
]}

机构：

[1] Med Univ Lodz, Dept Med Chem, Lodz, Poland

[2] Tech Univ Lodz, Inst Gen & Ecol Chem, PL-90924 Lodz, Poland

[3] Univ Rouen, CNRS, Lab Neuropsychopharmacol Expt, Rouen, France

[4] Tech Univ Lodz, Inst Organ Chem, PL-90924 Lodz, Poland

[5] Polish Acad Sci, Med Res Ctr, Warsaw, Poland

[6] Med Univ Lodz, Dept Pharmacodynam, Lodz, Poland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2005年 / 13卷 / 24期

关键词：

antinociceptive activity; binding studies; mu-opioid receptor agonists;

D O I：

10.1016/j.bmc.2005.07.051

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In this paper, we describe the synthesis of a series of endomorphin-2 analogs containing N-methylated amino acids, consecutively in each position. The mu-opioid receptor binding affinities of the new analogs were determined in the displacement experiments. Their in vivo antinociceptive activity was assessed in the hot-plate test in mice after central (icv) and peripheral (ip) administration. [Sar(2)]endomorphin-2, which had the highest mu-receptor affinity, also showed the strongest analgesic effect when administered centrally and was the only analog that retained activity after peripheral injection. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：6713 / 6717

页数：5

共 28 条

[1] Stability against enzymatic hydrolysis of endomorphin-1 analogues containing β-proline [J].