Synthesis and biological evaluation of flavan-3-ol derivatives as positive modulators of GABAA receptors

Kenneth N Mewett; Sebastian P Fernandez; Anmol K Pasricha; Alice Pong; Steven O Devenish; David E Hibbs; Mary Chebib; Graham A R Johnston; Jane R Hanrahan

doi:10.1016/j.bmc.2009.08.062

Synthesis and biological evaluation of flavan-3-ol derivatives as positive modulators of GABAA receptors

Bioorg Med Chem. 2009 Oct 15;17(20):7156-73. doi: 10.1016/j.bmc.2009.08.062. Epub 2009 Sep 4.

Authors

Kenneth N Mewett¹, Sebastian P Fernandez, Anmol K Pasricha, Alice Pong, Steven O Devenish, David E Hibbs, Mary Chebib, Graham A R Johnston, Jane R Hanrahan

Affiliation

¹ Adrien Albert Laboratory of Medicinal Chemistry, Department of Pharmacology, Faculty of Medicine, The University of Sydney, NSW 2006, Australia.

PMID: 19783443
DOI: 10.1016/j.bmc.2009.08.062

Abstract

We herein describe the synthesis and positive modulatory activities of a small library of flavan-3-ol derivatives on alpha(1)beta(2)gamma(2L) GABA(A) receptors. Structure-activity relationships of various substituents on the A, B and C rings were evaluated in a functional electrophysiological assay. A trans configuration and a 3-acetoxy moiety are essential for activity. Substitution of the B ring appears to be well tolerated, with substituents on the A ring playing a major role in determining activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Flavonoids / chemical synthesis*
Flavonoids / chemistry
Flavonoids / pharmacology*
Magnetic Resonance Spectroscopy
Models, Molecular
Receptors, GABA-A / drug effects*
Structure-Activity Relationship

Substances

Flavonoids
Receptors, GABA-A
flavan-3-ol