Structure-activity relationship investigations of the modulating effect of core substituents on the affinity of pyrazoloquinolinone congeners for the benzodiazepine receptor.

Abstract A series of 6- and 7-substituted-2-arylpyrazolo[4,3- c ]quinolin-3-ones was synthesized and tested in vitro for binding with the benzodiazepine receptor in competition with [ 3 H]flunitrazepam. Electronic parameters (molecular electrostatic potential (MEP), charge distribution on the nitrogen atoms, dipole moment μ, and ionization potential (IP)) were calculated for the compounds by semi-empirical quantum chemistry methods. Lipophilicity of the compounds, expressed as logarithm of the octanol–water partition coefficient (log  P ), was calculated by the program Pallas. A quantitative correlation of the biological data with molecular parameters revealed a significant dependence ( r =0.95) of the activity on hydrophobic constants of the substituents, log  P , and magnitude of the MEP minimum associated with the carbonyl oxygen atom.