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

doi:10.1016/j.bmcl.2006.07.051

Bioorganic & Medicinal Chemistry Letters

Volume 16, Issue 20, 15 October 2006, Pages 5432-5435

https://doi.org/10.1016/j.bmcl.2006.07.051 Get rights and content

Abstract

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 abstract

The 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.

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Acknowledgments

The work at Clemson was supported by Grants DA03590 and DA15340 to J.W.H. and DA15579 to L.W.P.; that at Virginia Commonwealth University was supported by Grant DA03672 to B.R.M.

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

Abstract

Graphical abstract

Section snippets

Acknowledgments

Tetrahedron Lett.

Eur. J. Pharmacol.

Bioorg. Med. Chem. Lett.

Bioorg. Med. Chem.

J. Pharmacol. Exp. Ther.

J. Med. Chem.

1995 Symposium on the Cannabinoids

J. Org. Chem. USSR

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