Planning a QSAR study

This table shows some physicochemical parameters for six different substituents. If the most important physicochemical parameter for biological activity is jp, then the COCH3 group (0.50) would be a reasonable bioisostere for the SOCH3 group (0.49). If, on the other hand, the dominant parameter is it, then a more suitable bioisostere for SOCH3 (-1.58) would be S02CH3 (-1.63). 

When starting a QSAR study it is important to decide which physicochemical parameters are going to be studied and to plan the analogues such that the parameters under study are suitably varied. For example, it would be pointless to synthesize analogues where the hydrophobicity and steric volume of the substituents are correlated, if these two parameters are to go into the equation. 

It is also important to make enough structures to make the results statistically meaningful. As a rule of thumb, five structures should be made for every parameter studied. Typically, the initial QSAR study would involve the two parameters tt and a, and possibly Es. Craig plots could be used in order to choose suitable substituents. 

If there are two or more substituents, then the initial equation usually considers the total it and a contribution. 

As more analogues are made, it is often possible to consider the hydrophobic and electronic effect of substituents at specific positions of the molecule. Furthermore, the electronic parameter a can be split into its inductive and resonance components (F and R). Such detailed equations may show up a particular localized requirement for 

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