Synthesis and biological evaluation of pyrazolone analogues as potential anti-inflammatory agents targeting cyclooxygenases and 5-lipoxygenase.

New pyrazolone derivatives structurally related to celecoxib and FPL 62064 were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases (COXs) and 5-lipoxygenase (5-LOX) and their selectivity indices were calculated. The results showed that compounds 3f, 3h, 3l, and 3p have an excellent COX-2 selectivity index. Moreover, they showed potent 5-LOX inhibitory activity relative to celecoxib and zileuton, as positive controls.

New octahydroquinazoline derivatives: synthesis and hypotensive activity.

Several novel 1-(4-chlorophenyl)-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydro-5-oxo-3-(substitutedphenyl)quinazoline derivatives (2-21) structurally similar to prazosin, were prepared using Mannich reaction of 3-(4-chlorophenylamino)-5,5-dimethyl-2-cyclohexenone (1) with different aromatic amines in the presence of formaline. The structures of the quinazoline derivatives were established using elemental and spectral analyses. Compounds 18, 20 and 21 were found to possess a high hypotensive effect through their expected α(1)-blocking activity like the clinically used drug prazosin but with advantageous of being did not cause reflex tachycardia and having prolonged duration of action when tested in adrenaline-induced hypertension in anaesthetized rats.

Synthesis of new nonclassical acridines, quinolines, and quinazolines derived from dimedone for biological evaluation.

New nonclassical acridines, quinolines, and quinazolines were prepared starting from cyclic β-diketones, namely dimedone, through application of Hantzsch addition, Michael addition, and Mannich reactions, respectively. The antimicrobial activity revealed that decahydroacridin-1,8-dione 2e bearing a 3-nitrophenyl group and hexahydroquinoline 4e having a 2,4-dichlorophenyl moiety were the most active compounds against both Gram-positive and -negative bacteria based upon using the disc diffusion method. Cytotoxic activity studies for decahydroacridin-1,8-diones 2a-e against liver carcinoma cells (HepG(2)) using the MTT cell viability assay revealed that decahydroacridin-1,8-dione bearing a 4-methylphenyl moiety 2d showed a higher cytotoxic activity (IC(50) = 4.