Bisi Alessandra, Mokhtar Mahmoud Alì, Allará Marco, Naldi Marina, Belluti Federica, Gobbi Silvia, Ligresti Alessia, Rampa Angela
Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy.
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, National Research Council, Via Campi Flegrei 34, 80078 Pozzuoli, NA, Italy.
ACS Med Chem Lett. 2019 Feb 26;10(4):596-600. doi: 10.1021/acsmedchemlett.8b00594. eCollection 2019 Apr 11.
The discovery of the relevant role played by a dysregulation of the endogenous cannabinoid system in several pathological conditions has prompted an extensive research in this field. In this Letter, a series of cannabinoid receptor ligands bearing a previously unexplored polycyclic scaffold was designed and synthesized, in order to evaluate the potential of a new easily affordable privileged structure. The new compounds showed an appreciable affinity and a significant selectivity for the CB2 receptor and are endowed with an intriguing noncompetitive antagonist behavior. Due to the ability of the polycyclic structure to be easily modified in different ways, these compounds could represent convenient chemical tools to be exploited in order to better understand the endocannabinoid system impact on physiopathological conditions.
内源性大麻素系统失调在多种病理状况中所起的相关作用的发现，促使了该领域的广泛研究。在本信函中，设计并合成了一系列带有先前未探索过的多环骨架的大麻素受体配体，以评估一种新的易于获得的优势结构的潜力。新化合物对CB2受体表现出可观的亲和力和显著的选择性，并具有有趣的非竞争性拮抗行为。由于多环结构能够以不同方式轻松修饰，这些化合物可能代表方便的化学工具，可用于更好地理解内源性大麻素系统对生理病理状况的影响。
