1399049-84-3Relevant academic research and scientific papers
7-alkyl-3-benzylcoumarins: A versatile scaffold for the development of potent and selective cannabinoid receptor agonists and antagonists
Rempel, Viktor,Volz, Nicole,Hinz, Sonja,Karcz, Tadeusz,Meliciani, Irene,Nieger, Martin,Wenzel, Wolfgang,Br?se, Stefan,Müller, Christa E.
supporting information, p. 7967 - 7977 (2012/11/07)
A series of 7-alkyl-3-benzylcoumarins was designed, synthesized, and tested at cannabinoid CB1 and CB2 receptors in radioligand binding and cAMP accumulation studies. 7-Alkyl-3-benzylcoumarins were found to constitute a versatile scaffold for obtaining potent CB receptor ligands with high potency at either CB1 or CB2 and a broad spectrum of efficacies. Fine-tuning of compound properties was achieved by small modifications of the substitution pattern. The most potent compounds of the present series include 5-methoxy-3-(2-methylbenzyl)-7-pentyl-2H-chromen-2-one (19a, PSB-SB-1201), a selective CB1antagonist (Ki CB 1 0.022 μM), 5-methoxy-3-(2-methoxybenzyl)-7-pentyl-2H-chromen-2- one (21a, PSB-SB-1202), a dual CB1/CB2agonist (CB 1Ki 0.032 μM, EC50 0.056 μM; CB 2Ki 0.049 μM, EC50 0.014 μM), 5-hydroxy-3-(2-hydroxybenzyl)-7-(2-methyloct-2-yl)-2H-chromen-2-one (25b, PSB-SB-1203), a dual CB1/CB2 ligand that blocks CB 1 but activates CB2 receptors (CB1Ki 0.244 μM; CB2Ki 0.210 μM, EC50 0.054 μM), and 7-(1-butylcyclopentyl)-5-hydroxy-3-(2-hydroxybenzyl)-2H-chromen-2- one (27b, PSB-SB-1204), a selective CB2 receptor agonist (CB 1Ki 1.59 μM; CB2Ki 0.068 μM, EC50 0.048 μM).
