Studies in sympathomimetics

Abstract

After a historical account of the development of the knowledge of sympathomimetic drugs-from the discovery by Oliver and Schäfer of the blood pressure raising property of extracts of the adrenal gland, to the enunciation of the “phenyl ethylamine rule” by Barger and Dale-the literature up to 1946 on compounds functionally and structurally related to adrenaline, the most well known drug of this class, has been reviewed. The information relating to these drugs has been arranged to correlate the modification of physiological activity (mainly pressor action) with changes in molecular architecture.

PART II With the hope that 5 hydroxyadrenaline might possess pressor action more powerful than adrenaline, attempts were made for its synthesis, and compounds related to it. The difficulties encountered have been detailed, and wherever possible, explanations have been given for the causes of failure. Besides standardising the method of preparation of some compounds like triacetylgallic acid and triacetyl galloyl chloride, p bromo 3,4,5 triacetoxyacetophenone has been prepared in a purer form than previously obtained. The reaction between diazomethane and triacetyl galloyl chloride has been studied elaborately, and experimental evidence has been brought to support Dieterle Wieland’s explanation of the reaction mechanism.

PART III Section I 1 Aryl 2 thiol 4,5 diphenylimidazoles have been prepared by a new method. A number of new 1 aryl 2 thiol 4,5 diphenylimidazoles and their thioethers have been prepared, with a view to testing their pressor action and other pharmacological properties (especially morphine like activity). Section II This section describes the experiments carried out according to the plan to synthesise 2 arylmethyl imidazoles (potential pressor substances), which however was not successful. Except for p nitrophenylacetamidine, no new compound has been prepared. The condensation of p nitrophenylacetamidine with chloroacetone and benzoin has been studied.

PART IV Expecting to find useful pressor anaesthetics, various types of 2 arylamino 4,5 arylthiazoles, many of them new, have been studied. The reaction between aryl acyl halides and phenylthiobiuret has been studied for the first time. Although the work on the structure is not yet complete, two probable structures have been suggested, with reasons provided. Attempts to bring about the Fries rearrangement of naphthol chloroacetate have also been made.