QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF BENZODIAZEPINE-RECEPTOR LIGANDS .3.

By a quantitative structure-activity relationship (QSAR) study, the po tency of a series of structurally related ligands comprising 1-arylpyr azolo[4,5-c]quinolin-4-ones, 1-aryl[1]berizopyrano[3,4-d]pyrazol-4-one s, and 1-aryl[1]benzopyrano[4,3-b]pyrrol-4-ones (I), to displace a rad ioligand from its specific binding to the receptor, is shown to be sig nificantly correlated with steric (E(s)2,6) and hydrophobic (pi3,5) co nstants of aryl ring-substituents. Employing suitable indicator parame ters, the structural requirements within the tricyclic ring system is further highlighted. Additionally, the Free-Wilson approach for these congeners, after excluding 10 ''outliers'', assigns more activity-cont ributions to the more hydrophobic aryl meta-substituents, and negative contributions to the ortho-substituents, thereby corroborating the co nclusions drawn from the Hansch analysis. Regression analysis of anoth er series of ligands, dipyrazo-lo[5,4-b: 3',4'-d]pyridin-3-ones (II) r eveals that hydrophobicity of substituents in aryl ring lowers the lig and displacement ability. The tolerance of a bulky Ph group at R1, as reflected by the dummy parameter I(R)1, suggests a second anchoring si te at the receptor.