1-Alkyl-2-aryl-4-(1-naphthoyl)pyrroles: New high affinity ligands for the cannabinoid CB1 and CB2 receptors

Two series of 1-alkyl-2-aryl-4-(1-naphthoyl)pyrroles were synthesized and their affinities for the cannabinoid CB1 and CB2 receptors were determined. In the 2-phenyl series (5) the N-alkyl group was varied from n-propyl to n-heptyl. A second series of 23 1-pentyl-2-aryl-4-(1-naphthoyl)-pyrroles (6) was also prepared. Several compounds in both series have CB1 receptor affinities in the 6–30 nM range. The high affinities of these pyrrole derivatives relative to JWH-030 (1, R = C5H11) support the hypothesis that these pyrroles interact with the CB1 receptor primarily by aromatic stacking.

Graphical abstractThe synthesis and pharmacology of 28 1-alkyl-2-aryl-4-(1-naphthoyl)pyrroles are described. Several of these compounds have high affinity for both the CB1 and CB2 receptors.Figure optionsDownload full-size imageDownload as PowerPoint slide