A New Class of Antimicrobial Agents

Abstract

THE mesoionic 1,3,4-thiadiazoles, I, were first reported by Busch¹, who assigned a bicyclic structure to the compounds. Schoenberg² later re-examined the structure of Busch and offered a resonance hybrid structure, now accepted as being typical of a large group of heterocycles described as being mesoionic³. We became interested in the mesoionic 1,3,4-thiadiazoles as a natural extension of our interest in the pharmacology and pharmaceutical chemistry of the sydnones II^4–7. It occurred to us that since the two ring systems are isoelectronic (that is, being mesoionic they both possess an aromatic, positively charged, 5-membered ring, and a balancing negative charge on an exocyclic atom) the possibility might exist that the two ring systems could also be bioisosteric. That is, the ring itself may behave as a pharmacologically active functional group and that this already expressde similarity between the ring systems may impart similar pharmacological activity. A more conservative speculation would be that perhaps the mesoionic 1,3,4-thiadiazole ring system would have some prominent pharmacological activity.