Cyclic enkephalin analogues with exceptional potency and selectivity for delta-opioid receptors

被引：34

作者：

Hruby, VJ ^{[1
]}

BartoszBechowski, H ^{[1
]}

Davis, P ^{[1
]}

Slaninova, J ^{[1
]}

Zalewska, T ^{[1
]}

Stropova, D ^{[1
]}

Porreca, F ^{[1
]}

Yamamura, HI ^{[1
]}

机构：

[1] UNIV ARIZONA,DEPT PHARMACOL,TUCSON,AZ 85721

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1997年 / 40卷 / 24期

关键词：

D O I：

10.1021/jm9704762

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Superpotent and highly delta-opioid receptor selective cyclic peptides of the general formula H-Tyr-c[D-Pen-Gly-Phe(p-X)-Pen]-Phe-OH (where X = hydrogen or halogen) have been synthesized. In the binding assays the most selective and most potent compound is the p-bromophenylalanine-4 analogue (IC50 value = 0.19 nM, selectivity ratio = 21 000 for delta vs mu). In the GPI and MVD bioassays the most selective and most potent analogue is the p-fluoro-substituted analogue Tyr-[D-Pen-Gly-Phe(p-F)-Pen]-Phe-OH. In the MVD assay it has an exceptionally low IC50 value of 0.016 nM and a delta vs mu selectivity ratio of 45 000.

引用

页码：3957 / 3962

页数：6

共 45 条

[1] CHARACTERIZATION OF [H-3][ 2-D-PENICILLAMINE, 5-D-PENICILLAMINE] ENKEPHALIN BINDING TO DELTA-OPIATE RECEPTORS IN THE RAT-BRAIN AND NEUROBLASTOMA-GLIOMA HYBRID CELL-LINE (NG-108-15) [J].