Structure–activity relationships and CoMFA of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic properties
- 作者：Ronald Palin ; John K. Clark ; Louise Evans ; Andrea K. Houghton ; Philip S. Jones ; Alan Prosser ; Grant Wishart ; Kazuya Yoshiizumi
- 关键词：NOP/ORL1 agonist ; Antinociception ; Antiallodynia ; Pain ; CoMFA model
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2008
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 March 2008
- 卷：16
- 期：6
- 页码：2829-2851
- 文件大小：438 K
摘要
The N-3 position of a series of 3-phenoxypropyl piperidine benzimidazol-2-one analogues was optimised using the predictive power of a CoMFA model. The model was used to prioritise compounds for synthesis culminating in the triazole (+)-24. (+)-24 was found to be a high affinity, potent NOP agonist and demonstrated both antinociceptive and antiallodynic effects when administered iv to rodents.