The design of anti-inflammatory drugs: some considerations based on pessimism, molecular pharmacology and cellular pathology.

Professor Ariens in another context1 (and elsewhere in this Symposium) has drawn attention to the possibilities of molecular pharmacology serving as a guide to the development of new drugs. In pursuit of this theme, I should like to examine with you later in this lecture some of the biological and molecular characteristics of the principal non-steroid anti-inflammatory drugs known to us today, in order to discover which various properties ought to be associated with a particular chemical compound if it is to predictably manifest anti-inflammatory activity in animals and hopefully, anti-arthritic activity in man. This is what might be called the multianalytical approach to drug research since it may be summarized as in Figure 1. This familiar, widely employed and apparently rational approach, given a suitable lead, was brilliantly illustrated by the development of the quinoline antimalarials and the benzoate esters used as local anaesthetics following the labours of devoted and inquisitive medicinal chemists who wanted quite simply to know why quinine and cocaine respectively manifested their well-known pharmacological activities. This analytical-cum-synthetic approach was deservedly successful in disclosing new chemical species with pharmacological characteristics which were qualitatively similar to, but quantitatively and therapeutically superior to, those of the two particular alkaloids which provided the appropriate lead (both chemically and