University of Eastern Finland, Kuopio, Finland.
Bioorg Med Chem. 2011 Jan 15;19(2):939-50. doi: 10.1016/j.bmc.2010.11.059. Epub 2010 Dec 9.
Quinoline, isoquinoline, quinoxaline, and quinazoline derivatives were synthesized using microwave-assisted synthesis and their CB1/CB2 receptor activities were determined using the [³⁵S]GTPγS binding assay. Most of the prepared quinoline, isoquinoline, and quinoxalinyl phenyl amines showed low-potency partial CB2 receptor agonists activity. The most potent CB2 ligand was the 4-morpholinylmethanone derivative (compound 40e) (-log EC₅₀ = 7.8; E(max) = 75%). The isoquinolin-1-yl(3-trifluoromethyl-phenyl)amine (compound 26c) was a high efficacy CB2 agonist (-log EC₅₀ = 5.8; E(max) = 128%). No significant CB1 receptor activation or inactivation was shown in these studies, except 40e, which showed weak CB1 agonist activity (CB1 -log EC₅₀ = 5.0). These ligands serve as novel templates for the development of selective CB2 receptor agonist.
喹啉、异喹啉、喹喔啉和喹唑啉衍生物采用微波辅助合成法合成，并通过[³⁵S]GTPγS 结合测定法测定它们对 CB1/CB2 受体的活性。大多数合成的喹啉、异喹啉和喹喔啉基苯甲胺表现出低效力的部分 CB2 受体激动剂活性。最有效的 CB2 配体是 4-吗啉基甲酮衍生物（化合物 40e）（-log EC₅₀ = 7.8；E(max) = 75%）。异喹啉-1-基（3-三氟甲基-苯基）胺（化合物 26c）是一种高效 CB2 激动剂（-log EC₅₀ = 5.8；E(max) = 128%）。除 40e 外，这些研究中未显示出对 CB1 受体的显著激活或失活作用，40e 显示出弱的 CB1 激动剂活性（CB1 -log EC₅₀ = 5.0）。这些配体可作为开发选择性 CB2 受体激动剂的新型模板。
