Mj. Fray et al., STRUCTURE-ACTIVITY-RELATIONSHIPS OF 3-HYDROXY-2(1H)-QUINOLINONES AS N-METHYL-D-ASPARTATE (GLYCINE SITE) RECEPTOR ANTAGONISTS, Medicinal chemistry research, 6(9), 1996, pp. 581-592
Two series of 3-hydroxy-2(1H)-quinolinones (3a-s, 4a-v) were prepared
and structure-activity relationships for binding affinity to the N-met
hyl-D-aspartate (glycine site) receptor measured. Despite the structur
al similarity to glycine antagonists of the quinoxalinedioned type, su
rprisingly, the SARs for compounds 3a-s more closely follow those of t
he kynurenic acids. Thus the most potent compounds, 3r (IC50 = 6.3 nM)
and 4v (IC50 = 7.6 nM), possessed chlorines at both 5 and 7 positions
, and a suitable hydrogen-bond acceptor (ethoxycarbonyl or N,N'dialkyl
-ureido) at the 4-position.