A series of substituted 3H-1,2,3,5-oxathiadiazole-2-oxides (6) was prepared and tested for antihyperglycemic activity in the db/db mouse, a model for type 2 (non-insulin dependent) diabetes mellitus. The oxathiadiazoles 6 were synthesized by a two-step sequence: treatment of a substituted acetonitrile (4) with hydroxylamine to give the corresponding amidoxime (5) and cyclization with thionyl chloride to yield 6. In terms of potency, the 2-naphthalenylmethyl group (as in compound 3) was found to be the optimal substituent in this series. Compound 3 was approximately 5 times more potent than ciglitazone (1).

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A synthesis of the 4,5‐dihydro derivatives of the previously known pyrazolo[3,4‐a]acridine ring system is described. The reaction of a 3,4‐dihydroacridin‐1(2H)‐one with N,N‐dimethylformamide dimethyl acetal gave a reactive enamino ketone, which yielded the desired heterocycle upon reaction with hydrazine. Using this chemistry, 11‐amino‐4,5‐dihydro‐2H‐pyrazolo[3,4‐a)acridine (3) and a number of its 2‐substituted derivatives 4a‐k were synthesized and evaluated as acetylcholinesterase inhibitors, based on their relationship to 1,2,3,4‐tetrahydro‐9‐acridinamine (THA). 1‐Amino‐4,5‐dihydro‐1H‐pyrazolo[3,4‐a]acridine (11a) and 2‐amino‐4,5‐dihydro‐1H‐pyrazolo[3,4‐a]acridine (11b) were also synthesized and investigated as potential cholinesterase inhibitors.

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4,5‐Dihydro‐3‐(4‐pyridinyl)‐thieno[4,3,2‐ef][1,4]benzoxazepine maleate 2 has been synthesized from 3‐amino‐4‐fluorobenzo[fc]thiophene by employing an intramolecular nucleophilic aromatic fluoride displacement. In the presence of strong base and heat, 2 rearranges to form the isomeric hemiaminal, 3,4‐dihydro‐4‐methyl‐3‐(4‐pyridinyl)thieno[4,3,2‐ef][1,3]benzoxazine 10. A proposed mechanism for this rearrangement is discussed.