Studies on Quantitative Structure-Activity Relationships. IV. Usefulness of the Novel Substituent Entropy Constant σ_<s^o> and the Sign of the Enthalpy Parameter

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Biological response (BR) can be expressed by the equation BR=α (σ_<s^o>)^2+bσ_<s^o>+cσ_i+dσ_x+e for quantitative structure-activity relationships (QSAR) analyses. The values of σ_i and σ_x originally take+or-sign depending on the electronic character of the substituent group and can be used to describe strong drug-site interactions. On the contrary, original chemical significance is lost in |σ_i| and |σ_x|, which can be applied to weak drug-site interaction, where dipole-dipole or dispersion interaction could be predominant. The coefficient c of the BR equation becomes the same in meta- and para-substituted benzene series. When σ_x is real, σ_x/_m+σ_x/_p gives a better result than σ_x/_<m, p>, while on the other hand, when σ_x is absolute, |σ_x|/_<m, p> gives a good result. As regards the entropy term a (σ_<s^o>)^2+bσ_<s^o>, the ortho-substituted benzene series requires the+sign for a and the-for b, whereas for meta-and para-substituted series, this is reversed. When the relative weight of the entropy term decreases and the contribution of the enthalpy term becomes predominant, the quantum chemical index could often be used as an effective scale for BR.
公益社団法人日本薬学会の論文
1982-09-25