Antagonists of the CB1 receptor can be useful in the treatment of several important disorders. However, to date, the only clinically approved CB1 receptor antagonist, rimonabant, was withdrawn because of adverse central nervous system (CNS)-related side effects. Since rimonabant's withdrawal, several groups are pursuing peripherally selective CB1 antagonists. These compounds are expected to be devoid of undesirable CNS-related effects but maintain efficacy through antagonism of peripherally expressed CB1 receptors. Reported here are our latest results toward the development of a peripherally selective analog of the diphenyl purine CB1 antagonist otenabant 1. Compound 9 (N-{1-[8-(2-chlorophenyl)-9-(4-chlorophenyl)-9H-purin-6-yl]piperidin-4-yl}pentana mide) is a potent, orally absorbed antagonist of the CB1 receptor that is >50-fold selective for CB1 over CB2, highly selective for the periphery in a rodent model, and without efficacy in a series of in vivo assays designed to evaluate its ability to mitigate the central effects of Delta9-tetrahydrocannabinol through the CB1 receptor
Peripherally Selective Diphenyl Purine Antagonist of the CB1 Receptor
Fulp, A., Bortoff, K., Zhang, Y., Snyder, R., Fennell, T., Marusich, J., Wiley, J., Seltzman, H., & Maitra, R. (2013). Peripherally Selective Diphenyl Purine Antagonist of the CB1 Receptor. Journal of Medicinal Chemistry, 56(20), 8066-8072. https://doi.org/10.1021/jm401129n
Abstract
Publications Info
To contact an RTI author, request a report, or for additional information about publications by our experts, send us your request.
Meet the Experts
View All ExpertsRecent Publications
Article
The daily association between affect and alcohol use: A meta-analysis of individual participant data
Article
Protection of forest ecosystems in the eastern United States from elevated atmospheric deposition of sulfur and nitrogen
Article
The use of patient experience feedback in rehabilitation quality improvement and codesign activities
Article