Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA 19341, USA.
Bioorg Med Chem Lett. 2010 Jan 1;20(1):387-91. doi: 10.1016/j.bmcl.2009.10.062. Epub 2009 Oct 17.
A lead optimization campaign in our previously reported sulfamoyl benzamide class of CB(2) agonists was conducted to improve the in vitro metabolic stability profile in this series while retaining high potency and selectivity for the CB(2) receptor. From this study, compound 14, N-(3,4-dimethyl-5-(morpholinosulfonyl)phenyl)-2,2-dimethylbutanamide, was identified as a potent and selective CB(2) agonist exhibiting moderate in vitro metabolic stability and oral bioavailability. Compound 14 demonstrated in vivo efficacy in a rat model of post-surgical pain.
我们对之前报道的磺酰胺基苯甲酰胺类 CB(2) 激动剂进行了先导化合物优化研究，旨在改善该系列化合物的体外代谢稳定性，同时保持对 CB(2) 受体的高活性和选择性。通过这项研究，我们确定了化合物 14（N-(3,4-二甲基-5-(吗啉磺酰基)苯基)-2,2-二甲基丁酰胺）为一种有效的 CB(2) 激动剂，具有中等的体外代谢稳定性和口服生物利用度。化合物 14 在术后疼痛大鼠模型中表现出体内疗效。
