Author(s)

Jakob Nilsson, Elsebet Østergaard Nielsen, Tommy Liljefors, Mogens Nielsen, Olov Sterner

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3-Arylisothiazolo[5,4-b]quinolin-4(9H)-ones and 3-arylisoxazolo[5,4-b]quinolin-4(9H)-ones were synthesized and assayed for affinity for the benzodiazepine binding site of the GABAA receptors. While the 3-arylisothiazoloquinolin-4-ones were found to be potent ligands, with affinities (expressed as the affinity Ki value) down to 1 nM, the 3-arylisoxazoloquinolin-4-ones are less potent. This is suggested to depend on sterical repulsive interaction of the 3-arylisoxazoloquinolin-4-ones with the receptor essential volume of the binding site, and a higher electron density at the nitrogen in the azole ring (N-2) as well as the carbonyl oxygen in the isothiazoloquinolin-4-ones enabling them to interact stronger with hydrogen bond donor sites at the binding site.

Isothiazolo[5, 4-b]quinolin-4(9H)-ones; Isoxazolo[5, 4-b]quinolin-4(9H)-ones; Benzodiazepine binding site; GABAA Receptors; GABAA Receptor Subtypes; Pharmacophore Model

Nilsson, J. , Nielsen, E. , Liljefors, T. , Nielsen, M. and Sterner, O. (2012) 3-Arylisothiazoloquinols As Potent Ligands for the Benzodiazepine Site of GABA_A Receptors. Journal of Biomedical Science and Engineering, 5, 1-9. doi: 10.4236/jbise.2012.51001.