Solvay Pharmaceuticals, Research Laboratories, CJ van Houtenlaan 36, 1381 CP Weesp, The Netherlands.
Bioorg Med Chem Lett. 2010 Feb 1;20(3):1084-9. doi: 10.1016/j.bmcl.2009.12.032. Epub 2009 Dec 11.
The synthesis and structure-activity relationship studies of imidazoles are described. The target compounds 6-20 represent a novel chemotype of potent and CB(2)/CB(1) selective cannabinoid CB(2) receptor antagonists/inverse agonists with very high binding efficiencies in combination with favourable logP and calculated polar surface area values. Compound 12 exhibited the highest CB(2) receptor affinity (K(i)=1.03 nM) in this series, as well as the highest CB(2)/CB(1) subtype selectivity (>9708-fold).
描述了咪唑的合成和构效关系研究。目标化合物 6-20 代表了一种新型的强效、CB(2)/CB(1)选择性大麻素 CB(2)受体拮抗剂/反向激动剂的化学型，具有非常高的结合效率，结合有利的 logP 和计算的极性表面积值。在该系列中，化合物 12 表现出最高的 CB(2)受体亲和力（K(i)=1.03 nM），以及最高的 CB(2)/CB(1)亚型选择性（>9708 倍）。
