Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, United States.
J Med Chem. 2011 Jan 13;54(1):382-6. doi: 10.1021/jm100982d. Epub 2010 Dec 3.
An SAR study on the Dmt-substituted enkephalin-like tetrapeptide with a N-phenyl-N-piperidin-4-ylpropionamide moiety at the C-terminal was performed and has resulted in highly potent ligands at μ and δ opioid receptors. In general, ligands with the substitution of D-Nle(2) and halogenation of the aromatic ring of Phe(4) showed highly increased opioid activities. Ligand 6 with good biological activities in vitro demonstrated potent in vivo antihyperalgesic and antiallodynic effects in the tail-flick assay.
对在 C 末端具有 N- 苯基-N- 哌啶-4- 基丙酰胺部分的 Dmt 取代的脑啡肽样四肽进行了 SAR 研究,结果得到了在 μ 和 δ 阿片受体上具有高活性的配体。一般来说,具有 D-Nle(2)取代和苯环卤化的配体显示出高度增加的阿片活性。在体外具有良好生物活性的配体 6 在尾部闪烁试验中表现出有效的体内抗痛觉过敏和抗触觉异常作用。