Lovett J A, Portoghese P S
J Med Chem. 1987 Jul;30(7):1144-9. doi: 10.1021/jm00390a005.
A series of N,N-dialkylated leucine enkephalins were prepared in order to study the effect of substitution on antagonist activity at the delta opioid receptor. The target peptides 1-7 were evaluated in the mouse vas deferens (MVD) and guinea pig ileum (GPI) at 1 microM. All of the compounds except [N,N-di-2-phenethyl,Leu5]enkephalin (7) showed antagonist activity in the MVD against the delta receptor agonist [D-Ala2,D-Leu5]enkephalin. The most potent congener, [N,N-dibenzyl,Leu5]enkephalin (3), was 2.5-fold more potent than [N,N-diallyl,Leu5]enkephalin (1). None of the compounds at 1 microM showed any antagonist activity against agonists for other receptor types. The N,N-di-2-phenethyl (7) and N,N-dioctyl (6) analogues showed significant agonist activity at 1 microM in the MVD.
为了研究取代基对δ阿片受体拮抗剂活性的影响，制备了一系列N，N-二烷基化亮氨酸脑啡肽。在小鼠输精管（MVD）和豚鼠回肠（GPI）中以1μM的浓度对目标肽1-7进行了评估。除了[N，N-二-2-苯乙基，Leu5]脑啡肽（7）之外，所有化合物在MVD中对δ受体激动剂[D-Ala2，D-Leu5]脑啡肽均表现出拮抗剂活性。最有效的同系物[N，N-二苄基，Leu5]脑啡肽（3）的效力比[N，N-二烯丙基，Leu5]脑啡肽（1）高2.5倍。在1μM浓度下，没有一种化合物对其他受体类型的激动剂表现出任何拮抗剂活性。N，N-二-2-苯乙基（7）和N，N-二辛基（6）类似物在MVD中以1μM的浓度表现出显著的激动剂活性。
