Aminopyrazine CB1 receptor inverse agonists
- 作者：David J. Wustrow ; George D. Maynard ; Jun Yuan ; He Zhao ; Jianmin Mao ; Qin Guo ; Mark Kershaw ; Jack Hammer ; Robbin M. Brodbeck ; Kristen E. Near ; Dan Zhou ; David S. Beers ; Bertr ; L. Chenard ; James E. Krau
- 关键词：Cannabinoid ; Rat obesity model ; Brain level ; CB1 inverse agonist ; Ex vivo receptor occupancy
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2008
- 期刊代码：10_0960894x
- 类别：ch
- 出版时间：1 June 2008
- 卷：18
- 期：11
- 页码：3376-3381
- 文件大小：157 K
摘要
A series of 5,6-diaryl-2-amino-pyrazines were prepared and found to have antagonist-like properties at the CB1 receptor. Subsequent SAR studies optimized both receptor potency and drug-like properties including solubility and Cytochrome-P450 inhibition potential. Optimized compounds were demonstrated to be inverse agonists and compared in vivo with rimonabant for their ability to inhibit food intake, to occupy central CB1 receptors and to influence hormonal markers associated with obesity.