1- Structure of the drug molecule affects the biological ativity in two ways: first, it affects its affinity to the receptor; second, it affects its physicochemical properties and hence its pharmacokinetics.
2- The relation between structure and physicochemical properties (PCP) can be quantified ((QSAR)) through the Hansch equation.
3- The relation between activity and partition coefficient (PC) is parabolic and not linear.Why?
4- π and σ are descriptors of the hydrophobic and electronic effects of substituents. They can have either +ve or -ve values. What is the significace of π and σ values?
5- Topliss scheme is generated through interactive SAR studies. It indicates whether activity favours increased or decreased lipophilicity; favours electron withdrawing or electron donating groups. The various chemical groups are arranged in what is called Craig plot (a 2 dimensional plot) to easily locate the π and σ values of groups.
6- Steric factors can be measured by two experimental methods and one computational method.
7- Experimental determination of π depends on the fact that the sum of π values of the groups constituting the molecule represents the PC.
8- Experimental determination of σ value depends on the effect of electron withdrawing or electron donating properties of a given group on the acidity (pKa) of benzoic acid.
9- Experimental determination of Es depends on the effect of a given group (larger than methyl) on the rate of hydrolysis (K) of substituted methylacetate.
The Hansch equation relating π, σ and Es is:
Log 1/C= -K π2+K’ π+ σρ+K’’Es+K’’’
Molar refractivity MR=
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