Polypharmacological approaches to drug design has become important in the recent years, This approach can be favorable for treating chronic, complex disorders where single target- based drugs can have limited benefits. Cannabinoid-1 receptor (CB1R) and the endocannabinoid signaling system is involved in regulating many physiological functions both in the CNS and the periphery. A series of dual-target compounds based on selective, peripheral blocking of the cannabinoid-1 receptor (CB1R) and iNOS was developed by our group recently. The first-generation, dual-target compounds revealed key structure-activity relationships and high efficacy in in vivo models of liver fibrosis. Building on this, a more soluble series of compounds were synthesized and evaluated in in vitro CB1 receptor binding and functional assays. The structure-activity relationship in this series will be discussed. Additionally, the development of a chromatography-free synthesis of a peripherally restricted, dual-target lead compound will also be discussed.

Synthesis and biological evaluation of dual-target peripheral CB1R antagonists

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.