SYNTHETIC AND ELECTROMETRIC STUDIES ON SOME BIOLOGICALLY ACTIVE SULPHUR AND NITROGEN COMPOUNDS

Abstract

Medicinal chemistry, although an interdisciplinary branch of science, is still categorised and studied under pure chemistry. From the chemists point of view it involves the isolation, characterisation, and synthesis of compounds that can be used in medicine for the prevention, treatment and cure of disease. Medicinal chemistry thus provides the chemical basis for the interdisciplinary field of therapeutics. The applied aspects include understanding and explanation of the mechanism of the action of drugs and knowledge of rela tionships between chemical structure and biological activity and an assessment of the biodynamic behaviour to the chemical reactivity and physical properties. The impact of the study of fundamental medicinal chemistry, has given a new impetus to chemical, biological, and engineering sciences. The discovery of the medicinal usefulness of a compound has always stimulated inquiry into the chemical reactions and improved methods of synthesis of similar substances. Likewise, methods of pharmacology, biology and physico-chemical studies have had to be improved and revised to meet the peculiar spectrum of action of new drugs. By contributing therapeutic agents, chemists have made possible some of the proudest achievements of human and veterinary medicine and animal husbandry. Chemists have created new drugs 2 and hormones, as well as vitamins and other essential biochemicals, and have developed new methods of productions. Investigations in medicinal chemistry, as in all science, are undertaken as an adventure of the human spirit, essentially an artistic enterprise, stimulated largely by curiosity and served by disciplined imagination. It is still unknown, in a single instance, the details of the events by which a drug or a metabolite exerts its biological effects. This greatly impairs prediction of the action of drugs and success in their design. The chances of devising a clinically useful medicinal chemical are indeed very slim, since several restrictive conditions are superimposed even on the best laboratory findings: high potency should be maintained in man, there should be a minimum of side effects and acute toxicity, and virtually no chronic toxicity. No wonder that only a very small number of novel drugs are introduced into clinical practice every year. Medical science as we know it now had its inception at the turn of the twentieth century. In its beginning it was purely empirical, without even a pretense of trying to devise principles of drug action. Medicinal scientists gratefully seized upon the few prototypes of therapeutically active compounds provided by nature or by sheer chance observations. The close and unguided imitation of these "lead" structures provided the scope of pharmaceutical chemistry. 3 The main concern of pharmaceutical chemistry has remained the analysis and preparation of drugs. Medicinal chemistry tries to be based on the ever-in creasing hope that biochemical ration ales for drug discovery may be found. The interpretation of drug action at the molecular level is the intellectual goal of medicinal chemistry. The unsolved problems of the relationships of chemical structure and biological activity make it advisable to arrange drugs according to their medicinal use. Too many compounds of a given structural type exert such a variety of biological activi ties that a classification by chemical structure would be inappropriate. Even one and the same drug usually acts on various types of cells and tissues in a given animal, although one activity may predominate. Only if one main biological syndrome is very pronounced the given structure can be identified primarily with such activity. The great advances of medicinal chemistry have been achieved by two types of investigators: those with the genius of prophetic logic, who have opened a new field by interpreting correctly a few well planned experiments, whether they pertained to the design of the mechanisms of action of drugs; and those who have varied patiently the chemical structures of physiologi cally active compounds until a useful drug could be evolved as a tool in medicine. Interest in this field has been stimulated by improved methods of biological test procedures.