الفهرس 
ACKNOWLEDGMENTSOnly 14 pages are availabe for public view
 |  | from | 192 |  |  |
| | | from | 192 | | |
Abstract
Some novel 2,6-disubstituted pyridazine-3(2H)-one derivatives were synthesized and
evaluated for in vitro COX-2 inhibitory efficacy. Compounds 2-{[3-(2-methylphenoxy)-6-
oxopyridazin-1(6H)-yl]methyl}-1H-isoindole-1,3(2H)-dione (64a), 2-propyl-6-(otolyloxy)
pyridazin-3(2H)-one (65a) and 2-benzyl-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazin-
3(2H)-one (75a) showed the most potent COX-2 inhibitory activity with IC50 of 0.19, 0.11 and
0.24 μM, respectively. Twelve compounds with the highest COX-2 selectivity indices were
selected and evaluated for their anti-inflammatory, analgesic and ulcerogenic activities.
Compounds 6a and 16a demonstrated the most potent and consistent anti-inflammatory activity
over the synthesized compounds that was significantly higher than celecoxib in carrageenan rat
paw edema model with milder ulcer scoring than indomethacin in ulcerogenicity screening.
Keywords: Pyridazinone, COX-1, COX-2, anti-inflammatory, analgesic activity,
Ulcerogenicity.