Balboni Gianfranco, Guerrini Remo, Salvadori Severo, Negri Lucia, Giannini Elisa, Bryant Sharon D, Jinsmaa Yunden, Lazarus Lawrence H
Department of Toxicology, University of Cagliari, I-09124, Cagliari, Italy.
J Med Chem. 2005 Dec 29;48(26):8112-4. doi: 10.1021/jm058259l.
N(1)-Alkylation of 1H-benzimidizole of the delta agonist H-Dmt-Tic-NH-CH(2)-Bid with hydrophobic, aromatic, olefinic, acid, ethyl ester, or amide (1-6) became delta antagonists (pA(2)=8.52-10.14). delta- and micro-Opioid receptor affinities were high (K(i)delta=0.12-0.36 nM and K(i)micro=0.44-1.42 nM). Only delta antagonism (pA(2)=8.52-10.14) was observed; micro agonism (IC(50)=30-450 nM) was not correlated with changes in alkylating agent or delta antagonism, and some compounds yielded mixed delta antagonism/micro agonism.
δ 激动剂 H-Dmt-Tic-NH-CH(2)-Bid 的 1H-苯并咪唑的 N(1)-烷基化,与疏水、芳香、烯烃、酸、乙酯或酰胺(1-6)反应后成为 δ 拮抗剂(pA(2)=8.52-10.14)。对 δ 和 μ 阿片受体的亲和力较高(K(i)δ=0.12-0.36 nM,K(i)μ=0.44-1.42 nM)。仅观察到 δ 拮抗作用(pA(2)=8.52-10.14);μ 激动作用(IC(50)=30-450 nM)与烷基化剂的变化或 δ 拮抗作用无关,并且一些化合物产生了混合的 δ 拮抗作用/μ 激动作用。