10.1016/j.bmc.2009.03.006
The study focuses on the synthesis and structure-activity relationship of novel diarylpyrazole imide analogues as CB1 cannabinoid receptor ligands, with the aim of finding potential anti-obesity drugs. The researchers synthesized a series of compounds based on the 1,5-diarylpyrazole template of rimonabant, a known CB1 receptor antagonist used for obesity treatment. They replaced the N-piperidinylcarboxamide group of rimonabant with sulfonamide, imide, N-methyl imide, and methylenediamide groups to optimize CB1 binding affinity. The synthesized compounds were evaluated for their in vitro rat CB1 receptor binding affinity, and some showed potent activities. The study also conducted in vivo efficacy tests and quantitative structure-activity relationship (QSAR) studies to explore the physicochemical properties affecting CB1 receptor binding affinity. The purpose of these chemicals was to develop new CB1 receptor antagonists that could potentially be used as anti-obesity drugs, with the goal of improving safety and efficacy over existing treatments.
10.1021/ml4004759
The research focuses on the design, synthesis, and testing of a series of bivalent ligands that target the heterodimers formed by Cannabinoid CB1 and Orexin OX1 receptors. The purpose of this study is to understand the interaction and roles of these receptor heterodimers in vitro and in vivo, which could potentially lead to novel therapeutic approaches for neurological disorders mediated by these receptors. The researchers synthesized bivalent ligands by combining the pharmacophores SR141716 (a CB1 antagonist) and ACT-078573 (an orexin antagonist). The study concluded that while most bivalent ligands showed reasonable potency at the CB1 receptor, they were largely inactive at the OX1 receptor. However, one compound with an 18-atom linker (compound 20) demonstrated enhanced activity against both receptors when coexpressed, suggesting a possible interaction with CB1-OX1 dimers.
