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SYNTHESIS AND BIOLOGICAL EVALUATION OF SUBSTITUTED TETRAHYDRO-1H-QUINO[7,8- B][1,4]BENZODIAZEPINE-3-CARBOXYLIC DERIVATIVES

YUSUF M. AL-HIARI¹, ASHOK K. SHAKYA^2*, MUHAMMED H. ALZWEIRI¹, TALAL ABURJAI¹, RANA ABU-DAHAB¹

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This research paper aims the preparation of substituted tetrahydroquino[7,8-b] [1,4]benzodiazepine-3-carboxylic acids 4a, 4b and 4c. Reaction of 7-chloro-1-cyclopropyl- 6-fluoro-8-nitro-1,4-dihydroquinoline-3-carboxylic acid (6) with each of 2-amino-5- methylbenzoic acid (5a), 2-amino-5-flourobenzoic acid (5b), and 2-amino-5-nitrobenzoic acid (5c) yielded 8-nitro-7-substituted anilino-1,4-dihydroquinoline-3-carboxylic acids 7 (a-c) with low yields. Reduction of 7 with sodium dithionite or stannous chloride resulted in the production of 8-amino-7-substituted aniline-1,4-dihydro-quinoline-3-carboxylic acids 10 (a-c). Polyphosphoric acid (PPA) catalyzed thermal lactamization of 10 resulted in the production of 4 (a-c). All intermediates and target compounds were characterized using elemental analysis, NMR, IR and MS spectral data. The prepared targets and the intermediates have shown interesting antibacterial activity mainly against Gram positive strains. In particular, the reduced intermediates 10 (a-c) showed good activity against standard S. aureus (MIC = 0.05 - 0.19 μg/mL). Intermediates 10 (a-c) have also shown reasonable activity against resistant gram positive strains. The targets 4b and 4c have comparable activity to the reference against standard gram positive strains.