Conversion of the potent δ-opioid agonist H-Dmt-Tic-NH-CH2-Bid into δ-opioid antagonists by N1-benzimidazole alkylation

被引：13

作者：

Balboni, G

Guerrini, R

Salvadori, S

Negri, L

Giannini, E

Bryant, SD

Jinsmaa, Y

Lazarus, LH ^{[1
]}

机构：

[1] Univ Cagliari, Dept Toxicol, I-09124 Cagliari, Italy

[2] Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy

[3] Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy

[4] Univ Roma La Sapienza, Dept Human Physiol & Pharmacol Vittorio Erspamer, I-00185 Rome, Italy

[5] NIEHS, Med Chem Grp, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 26期

关键词：

D O I：

10.1021/jm058259l

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

NI-Alkylation of 1H-benzimidizole of the delta agonist H-Dmt-Tic-NH-CH2-Bid with hydrophobic, aromatic, olefinic, acid, ethyl ester, or amide (1-6) became delta antagonists (pA(2) = 8.52-10.14). delta- and mu-Opioid receptor affinities were high (K-i delta = 0.12-0.36 nM and K-i mu = 0.44-1.42 nM). Only delta antagonism (pA(2) = 8.52-10.14) was observed; mu agonism (IC50 = 30-450 nM) was not correlated with changes in alkylating agent or delta antagonism, and some compounds yielded mixed delta antagonism/gamma agonism.

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页码：8112 / 8114

页数：3

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