The QSAR Application of a New Steric Parameter Set for Aromatic Substituents Defined by the Acidic Hydrolysis Rate of Ortho‐substituted Benzamides

Abstract

AbstractWe examined applications of a new steric parameter set for aromatic substituents, Es(AMD), recently defined by the rate constants for acidic hydrolysis of ortho‐substituted benzamides, to the QSAR study of biologically active compounds. The scale of the Es(AMD) constant was put as close as possible to that of the Taft‐Kutter‐Hansch (TKH) Es parameter. For alkyl and halogen substituents, the Es(AMD) value was very close to the TKH Es value, but not for methoxy, isopropoxy, and such planar π‐bonded substituents as NO2 and Ph. Agrochemical and medicinal activities of various series of aromatic compounds taken from our earlier studies and the literature were analyzed quantitatively in terms of steric, electronic, and hydrophobic parameters, and the correlation equations formulated with Es(AMD) and Es for the steric effect of substituents, mostly those at ortho positions to the functional group, were compared. For several series of compounds, the Es(AMD) value gave better results than the TKH Es.