Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Industries, Sinai University, Al-Arish, North Sinai, Egypt.
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
Arch Pharm (Weinheim). 2017 Sep;350(9). doi: 10.1002/ardp.201700093. Epub 2017 Aug 9.
Some novel 2,6-disubstituted pyridazine-3(2H)-one derivatives were synthesized and evaluated for in vitro cyclooxygenase-2 (COX-2) inhibitory efficacy. Compounds 2-{[3-(2-methylphenoxy)-6-oxopyridazin-1(6H)-yl]methyl}-1H-isoindole-1,3(2H)-dione (5a), 2-propyl-6-(o-tolyloxy)pyridazin-3(2H)-one (6a), and 2-benzyl-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazin-3(2H)-one (16a) showed the most potent COX-2 inhibitory activity with IC values of 0.19, 0.11, and 0.24 μM, respectively. The synthesized compounds with the highest COX-2 selectivity indices were 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, which was significantly higher than that of celecoxib in the carrageenin rat paw edema model and with milder ulcer scoring than that of indomethacin in the ulcerogenicity screening.
一些新型 2,6-二取代哒嗪-3(2H)-酮衍生物被合成并评估了其体外环氧化酶-2（COX-2）抑制活性。化合物 2-[[3-(2-甲基苯氧基)-6-氧代哒嗪-1(6H)-基]甲基]-1H-异吲哚-1,3(2H)-二酮（5a）、2-丙基-6-(邻甲苯氧基)哒嗪-3(2H)-酮（6a）和 2-苄基-6-(3,5-二甲基-1H-吡唑-1-基)哒嗪-3(2H)-酮（16a）表现出最强的 COX-2 抑制活性，IC 值分别为 0.19、0.11 和 0.24 μM。具有最高 COX-2 选择性指数的合成化合物被评估了其抗炎、镇痛和致溃疡活性。化合物 6a 和 16a 在合成化合物中表现出最强和最一致的抗炎活性，在角叉菜胶致大鼠足肿胀模型中明显高于塞来昔布，在致溃疡性筛选中溃疡评分比吲哚美辛更轻。
