Influence of the Side Chain Next to C-Terminal Benzimidazole in Opioid Pseudopeptides Containing the Dmt-Tic Pharmacophore
Influence of the Side Chain Next to C-Terminal Benzimidazole in Opioid Pseudopeptides Containing the Dmt-Tic Pharmacophore
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DOI：
10.1021/jm900686q
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发表时间：
2009-09-10
影响因子：
7.3
通讯作者：
Salvadori, Severo
中科院分区：
文献类型：
--
作者：
Balboni, Gianfranco;Trapella, Claudio;Salvadori, Severo
为改进先导化合物6-羟甲基-二氢-噻-天冬氨酸（H-Dmt-Tic-Asp*-Bid）的构效关系研究，我们合成并表征了一系列1H-苯并咪唑-2-基（Bid）侧链被不同化学性质取代的类似物。获得了有趣的结果：（1）只有Gly、Ala和Asp产生δ激动作用，（2）Phe产生δ拮抗作用，（3）除Glu（无任何活性）外的所有其它残基产生μ激动作用。
To improve the structure-activity studies of the lead 6 opioid agonist H-Dmt-Tic-Asp*-Bid, we synthesized and pharmacologically characterized a series of analogues in which the side chain next to 1H-benzimidazole-2-yl (Bid) was substituted by those endowed with different chemical properties. Interesting results were obtained: (1) only Gly, Ala, and Asp resulted in delta agonism, (2) Phe yielded delta antagonism, (3) and all other residues except Glu (devoid of any activity) gave mu agonism.