Synthesis and evaluation of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one analogues as NOP receptor agonists with analgesic and sedative properties
- 作者：Ronald Palin ; Anton Bom ; John K. Clark ; Louise Evans ; Helen Feilden ; Andrea K. Houghton ; Philip S. Jones ; Brian Montgomery ; Mark A. Weston ; Grant Wishart
- 关键词：NOP ; ORL1 ; Antinociception ; Analgesic ; Sedative ; Benzimidazolone
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2007
- 期刊代码：9_09680896
- 类别：ch
- 出版时间：15 February 2007
- 卷：15
- 期：4
- 页码：1828-1847
- 文件大小：380 K
摘要
A series of 3-phenoxypropyl piperidine benzimidazol-2-one analogues have been discovered as novel NOP receptor agonists. Structure–activity relationships have been explored via N-3 substitution of the benzimidazol-2-one with a range of functionality. The N-methyl acetamide derivative (+)-7f was found to be a high-affinity, potent NOP agonist with greater than 100-fold selectivity over the MOP receptor. Furthermore (+)-7f was shown to be both antinociceptive and sedative when administered iv to rodents.