SYNTHESIS OF 2-TRIFLUOROMETHYL-4,7-DIHYDRO-7- OXO-(1,2,4)TRIAZOLO[1,5-a]PYRIMIDINE-6-CARBOXYLIC ACID DERIVATIVES AS POTENTIAL ANTIMYCOBACTERIAL AND ANTIMICROBIAL AGENTS

Syntheses of the target compounds were achieved by reaction of
3-amino-5-trifluoromethyl-1,2,4-triazole 1 and diethylethoxymethylenemalonate
(DEEM) in glacial acetic acid to afford
ethyl 2-(trifluoromethyl)-4,7-dihydro-7-oxo[1,2,4]-triazolo[1,5-
a]pyrimidine-6-carboxylate 2. Reaction of compound 2 with
hydroxylamine hydrochloride gave hydroxamic acid 3, while
reaction with hydrazine hydrate in methanol gave the
corresponding carbohydrazide 4. Schiff bases of compound 4 with
appropriate aldehyde yielded series 5a-g. Refluxing of hydrazide 4
with appropriate isothiocyanate gave thiosemicarbazides 6a-f.
The antimycobacterial evaluation was determined against
Mycobacterium tuberculosis H37Rv(ATCC 27294). Compound 5e
and 5b showed activity with IC90(6.672, 7.362 μg/ml respectively) and IC50 (4.627, 6.382 μg/ml respectively). In vitro antibacterial
screening for the prepared compounds were determined against
certain strains of gram positive and gram negative bacteria. The
results showed that compounds 3, 5a, 6b possessed higher activity
than ampicillin against all strains, also the activity range from half
to sixth activity of nalidixic acid against E. coli. Compounds 3, 5a,
5b, 5c, 5f, 6b exhibited activity against P. aeruginosa, while
nalidixic acid possessed no activity. Compounds 3, 5a, 5b and 6b
possessed antifungal activity.