Correlations Todays perspective

This chapter has traced the slow, hesitant steps by which drug workers have advanced beyond the belief that structure—action relationships depended on particular substituents or nuclei, and how they gradually learnt to appreciate the importance of physical properties. At the present time it is considered that three properties are most relevant (i) partition, (ii) ionization (or other 

With these principles in mind, it has proved profitable sometimes to replace carbon by nitrogen as in the highly successful insecticide that has been made from octopamine (2.55), an important neurotransmitter in insects. Here — N CH— was substituted for the —CH(OH)—CH2-group, creating a new series of insecticides of which chlordimeform 2.36) was the best. It gives the insect an overdose of agonistic activity (Evans and Gee, 1980). 

No less stimulating to the drug designer was the replacement of all five chlorine atoms in DDT (2.37) by methyl- or methoxy-groups [giving 1,1- 

In a final analysis, we must ask ourselves what we mean when we speak of structure—activity relations When we say structure , in this connexion, we surely mean constitution , namely all the information on physical and chemical properties that is stored in the chemical formula, or that can be discovered by measurement and experimentation. Also when we say activity we mean the action on the drug-receptor, but this effect, we know, is often connected to the desired physiological result only through a long chain of other reactions. It is only with reference to the action at the receptor that the constitution of the drug has any relevance. 

Similarly the formula of pyridine reveals that it is a weak base, with a pK about 5, and the basic strength of substituted pyridines can quickly be calculated by the procedures of Perrin, Dempsey and Serjeant (1981). Further, 

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