Solutions For An Introduction to Medicinal Chemistry Chapter 18 Problem 2Q

There are 4 quadrants in the Craig plot. They are +π –σ; +π +σ; -σ –π and + σ –π. Analogues of lead compound should be synthesized with the substituents from each quadrant.

Once, the Hansch equation has been derived, it would help an individual to know, whether, π (pie) and σ (sigma) should be positive or negative. It is so, in order to get the increased biological activity as compared to the lead compound.

Further, development would, then, concentrate on substituents from the relevant quadrant. The Craig plot is described as follows along with the given substituents as follows:

Figure: The Craig plot with concerned substituents in the quadrants.

After looking at the plot, it is evident that the substituents given for study have wide range of hydrophobicity constants. Therefore, they are good for studies that involve hydrophobicity property.

Yet, all have +σ (positive sigma) values, which indicates their electron withdrawing nature. Therefore, they cannot be appropriate for the comparison of electronic effects of different substituents of the biological activity.