Study Comparing Hansch Analysis and CoMFA

In 1993, Martin and colleagues performed a follow-up study on the same 15 compounds using CoMFA. CoMFA does not produce a simple equation in the manner of Hansch analysis, but CoMFA does calculate activities for the training set compounds. Comparing the predicted and experimental activities allows determination of the model s correlation coefficient. The CoMFA performed by Martin gave an r-value of 0.96. Martin s CoMFA model accounted 

To continue the comparison, Martin prepared an additional set of 12 analogues of 12.18 and determined their activity against the 5-HT2 receptor. Both Nelson s Hansch equation and Martin s CoMFA model were used to generate calculated activities of the 12 new compounds. The summary of the findings is shown in Table 12.8. 

Entry Exptl. pKj Hansch Calc. pKj Diff. CoMFA Calc. pKj Diff.  

The root mean square (RMS) of the differences between the experiment and predicted values for the Hansch equation was 0.75, while the CoMFA gave 0.65. A smaller value for the RMS of the differences indicates CoMFA afforded a more accurate model. 

The data in Table 12.8 do not represent a resounding victory for CoMFA over Hansch analysis. However, a significant advantage of CoMFA is its flexibility. Martin continued his study by including an additional 30 compounds in his CoMFA model. The additional compounds are analogous to 12,18 but contain significantly more structural variability with R-group modifications at C-2, 

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