Hansch analysis Taft steric parameter

Analysis of the Hansch descriptors illustrates that increasing the lipophilicity property for this series of compounds will increase the bioactivity in a more dramatic fashion than increasing the Tafts steric parameter. Increasing the water accessible surface area (MOE descriptor) will increase the bioactivity of the compounds. But there is more than just adding lipophilicity and water accessible surface area to the molecules to increase binding affinity. A comparison of the substituents to the bioactivities illustrates that the bulkier X and Y groups increase bioactivity in conjunction with atomic partial charge distribution of the substituents. 

The activity of 1,1jl-trifluoro 3-mercapto substituted phenyl propan-2-ones was not simply correlated with MR alone, therefore, a combination of Hammett a constant, Taft steric parameter (Eg) and Hansch hydrophobic constant (x) was included in the regression analysis. "Equation 36" was found to be of the best fit for compounds substituted in the meta and para positions. 

BR is the relative biologic activity under investigation, for example the molar EDr>o or the percent response at a given dose. Log P is the logarithm of the octanol-water partition coefficient, a is the approprite Hammett signa constant (electronic in nature), and Es is the Taft steric parameter. With the important demonstration by Hansch that the partition coefficient is often an additive constitutive property, all of the physical parameers may be obtained from the literature. A second important contribution by Hansch is the recognition that the use of statistical techniques is essential to the analysis of quantitative structure-activity relationships. To develop an equation such as that above, one feeds the... 

Examining 18 substituted 3-phenylthio-1,1,1-trlfluoro-2-propanones, regression equations were obtained between the inhibitory activities and the Hammett (ct), Taft (E ) steric and Hansch (ir) hydrophobicity constants (H). In the fiope of increasing the significance of these equations and to better distinguish between the Importance of various substituent positions, several new compounds of the related structure were synthesized, a much larger set of substituent parameters was applied, and instead of the arbitrary choice of these values, the variables were selected into the equations by a more sophisticated tool, linear stepwise regression analysis. 

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