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Many unfavourable pharmacological and physicochemical properties of drugs can be improved by the application of prodrugs. Ring-chain tautomeric prodrugs include 1,3-X,N-heterocycles prepared from dysfunctional compounds with aldehydes or ketones. From the ring-chain equilibria of these derivatives, the open form undergoes continuous hydrolysis to give the bioactive molecule, which can be either the original dysfunctional compound or an oxo compound. This concept was applied in cases of oxazolidine and thiazolidine prodrugs derived from (-)-ephedrine, L-cysteine and hydrocortisone. From studies on 2-aryl-1,3-X,N-heterocycles, it has been unequivocally concluded that ring-chain tautomerism is characteristic not only for 1,3-O, N-heterocycles, but also for their 1,3-S,N- and 1,3-N,N-analogues. The ratios of the tautomeric forms involved in the equilibria of these systems are strongly influenced by the steric and electronic characters of the substituents. The results demonstrate that the transformation of a drug candidate to a ring-chain tautomeric prodrug is always worthy of consideration, when the pharmacologically active compound contains a 1,2- or 1,3-amino alcohol, a diamine or an amino thiol moiety or an oxo group.