5-sulfonyl-benzimidazoles as selective CB2 agonists

被引：32

作者：

Verbist, Bie M. P. ^{[1
]}

De Cleyn, Michel A. J. ^{[1
]}

Surkyn, Michel ^{[1
]}

Fraiponts, Erwin ^{[1
]}

Aerssens, Jeroen ^{[2
]}

Nijsen, Marjoleen J. M. A. ^{[1
]}

Gijsen, Harrie J. M. ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev, B-2340 Beerse, Belgium

[2] Tibotec BVBA, B-2800 Mechelen, Belgium

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 08期

关键词：

cannabinoid receptor CB2 agonist benzimidazole VlaaiVis; species difference;

D O I：

10.1016/j.bmcl.2008.03.048

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel series of benzimidazole CB2-receptor agonists was synthesized and the structure-activity relationship explored. The results showed agonistic activities with an EC50 up to 0.5 nM and excellent selectivity (> 4000-fold) over the CB1 receptor. The size of the substituent on the 2-position determined the level of agonism, ranging from inverse agonism to partial agonism to full agonism, which was more pronounced for the rat CB2 receptor. A wide variation of sulfonyl substituents at the benzimidazole 5-position was tolerated, which was used to optimize the drug-like properties. This resulted into lead compound 14j that can be used to investigate the potential of a selective, peripherically acting CB2 agonist. The in vitro pro. le of key compounds is displayed using pie bar charts (VlaaiVis). (c) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2574 / 2579

页数：6

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