Synthesis Antimicrobial and Hypoglycemic Activities of Novel N-(1-Adamantyl)carbothioamide Derivatives

摘要

The reaction of 1-adamantyl isothiocyanate >4 with the various cyclic secondary amines yielded the corresponding N-(1-adamantyl)carbothioamides >5a–>e, >6, >7, >8a–>c and >9. Similarly, the reaction of >4 with piperazine and trans-2,5-dimethylpiperazine in 2:1 molar ratio yielded the corresponding N,N'-bis(1-adamantyl)piperazine-1,4-dicarbothioamides >10a and >10b, respectively. The reaction of N-(1-adamantyl)-4-ethoxycarbonylpiperidine-1-carbothioamide >8c with excess hydrazine hydrate yielded the target carbohydrazide >11, in addition to 4-(1-adamantyl)thiosemicarbazide >12 as a minor product. The reaction of the carbohydrazide >11 with methyl or phenyl isothiocyanate followed by heating in aqueous sodium hydroxide yielded the 1,2,4-triazole analogues >14a and >14b. The reaction of the carbohydrazide >11 with various aromatic aldehydes yielded the corresponding N'-arylideneamino derivatives >15a–>g. The compounds >5a–>e, >6, >7, >8a–>c, >9, >10a, >10b, >14a, >14b and >15a–>g were tested for in vitro antimicrobial activity against certain strains of pathogenic Gram-positive and Gram-negative bacteria and the yeast-like fungus Candida albicans. The compounds >5c, >5d, >5e, >6, >7, >10a, >10b, >15a, >15f and >15g showed potent antibacterial activity against one or more of the tested microorganisms. The oral hypoglycemic activity of compounds >5c, >6, >8b, >9, >14a and >15b was determined in streptozotocin (STZ)-induced diabetic rats. Compound >5c produced significant reduction of serum glucose levels, compared to gliclazide.