苯并咪唑（Bid）在δ-阿片受体激动剂假肽H-Dmt-Tic-NH-CH(2)-Bid（UFP-502）中的作用
Role of benzimidazole (Bid) in the delta-opioid agonist pseudopeptide H-Dmt-Tic-NH-CH(2)-Bid (UFP-502).
作者信息
Salvadori Severo, Fiorini Stella, Trapella Claudio, Porreca Frank, Davis Peg, Sasaki Yusuke, Ambo Akihiro, Marczak Ewa D, Lazarus Lawrence H, Balboni Gianfranco
机构信息
Department of Pharmaceutical Sciences and Biotechnology Center, University of Ferrara, I-44100 Ferrara, Italy.
出版信息
Bioorg Med Chem. 2008 Mar 15;16(6):3032-8. doi: 10.1016/j.bmc.2007.12.032. Epub 2007 Dec 23.
Abstract
H-Dmt-Tic-NH-CH(2)-Bid (UFP-502) was the first delta-opioid agonist prepared from the Dmt-Tic pharmacophore. It showed interesting pharmacological properties, such as stimulation of mRNA BDNF expression and antidepression. To evaluate the importance of 1H-benzimidazol-2-yl (Bid) in the induction of delta-agonism, it was substituted by similar heterocycles: The substitution of NH(1) by O or S transforms the reference delta-agonist into delta-antagonists. Phenyl ring of benzimidazole is not important for delta-agonism; in fact 1H-imidazole-2-yl retains delta-agonist activity.
摘要
H-Dmt-Tic-NH-CH(2)-Bid（UFP-502）是首个由Dmt-Tic药效基团制备的δ-阿片受体激动剂。它展现出了有趣的药理学特性，比如刺激脑源性神经营养因子（BDNF）mRNA的表达以及具有抗抑郁作用。为了评估1H-苯并咪唑-2-基（Bid）在诱导δ-激动效应中的重要性，将其用类似的杂环进行取代：用氧或硫取代NH(1)会将参比δ-激动剂转变为δ-拮抗剂。苯并咪唑的苯环对于δ-激动效应并不重要；实际上，1H-咪唑-2-基保留了δ-激动剂活性。
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