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 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.
Mewett
Kenneth N
KN
Adrien Albert Laboratory of Medicinal Chemistry, Department of Pharmacology, Faculty of Medicine, The University of Sydney, NSW 2006, Australia.
Fernandez
Sebastian P
SP
Pasricha
Anmol K
AK
Pong
Alice
A
Devenish
Steven O
SO
Hibbs
David E
DE
Chebib
Mary
M
Johnston
Graham A R
GA
Hanrahan
Jane R
JR
D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D011963:Receptors, GABA-A / Q000187:drug effects*; D013329:Structure-Activity Relationship
D005419:Flavonoids; D011963:Receptors, GABA-A; C404987:flavan-3-ol