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

We herein describe the synthesis and positive modulatory activities of a small library of flavan-3-ol derivatives on α1β2γ2L GABAA 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.

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