Thienopyrimidine Derivatives as GPR55 Receptor Antagonists: Insight into Structure-Activity Relationship

GPR55 is an orphan G-protein coupled receptor involved in various pathophysiological conditions. However, there are only a few noncannabinoid GPR55 ligands reported so far. The lack of potent and selective GPR55 ligands precludes a deep exploration of this receptor. The studies presented here focused on a thienopyrimidine scaffold based on the GPR55 antagonist ML192, previously discovered by high-throughput screening. The GPR55 activities of the new synthesized compounds were assessed using beta- arrestin recruitment assays in Chinese hamster ovary cells over-expressing human GPR55. Some derivatives were identified as GPR55 antagonists with functional efficacy and selectivity versus CB1 and CB2 cannabinoid receptors.

Automated summary

This study focused on the exploration of GPR55 receptor and identified a thienopyrimidine scaffold-based GPR55 antagonist. The GPR55 activity of newly synthesized compounds was evaluated, and some derivatives with functional efficacy and selectivity against CB1 and CB2 cannabinoid receptors were discovered.