Design, Synthesis and Molecular Docking Study of Some Substituted 4,5-dihydro-2H-indazole Derivatives as Potential Anti-inflammatory Agents

被引：4

作者：

Badr, Mona H. ^{[1
,2
]}

Elbayaa, Rasha Y. ^{[2
]}

El-Ashmawy, Ibrahim M. ^{[3
]}

机构：

[1] King Abdulaziz Univ, Fac Pharm, Dept Pharmaceut Chem, Jeddah 21589, Saudi Arabia

[2] Univ Alexandria, Fac Pharm, Dept Pharmaceut Chem, Alexandria 21521, Egypt

[3] Univ Alexandria, Fac Vet Med, Dept Pharmacol, Alexandria 21521, Egypt

来源：

MEDICINAL CHEMISTRY | 2013年 / 9卷 / 05期

关键词：

Indazole; Anti-inflammatory activity; Ulcerogenic effect; Acute toxicity; COX-2; Docking; BIOLOGICAL EVALUATION; SELECTIVE INHIBITORS; ANTIPYRETIC ACTIVITY; PART; 5-LIPOXYGENASE;

D O I：

10.2174/1573406411309050012

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A new series of 4,5-dihydro-2H-indazoles was synthesized and evaluated for anti-inflammatory activity using formalin-induced paw edema and turpentine oil-induced granuloma pouch bioassays. In addition, the inhibitory activity of cyclooxygenase, ulcerogenic effect, and acute toxicity (ALD(50)) values were also determined. Compounds 10, 13, 15, 16, 18 and 22 were proved to display distinctive anti-inflammatory profiles with a fast onset of action. They revealed super GI safety profile and are well tolerated by the experimental animals with high safety margin (ALD(50) > 300 mg / Kg). The same active compounds exhibited moderate to powerful selectivity profile towards the inhibition of COX-2 enzyme. Docking poses for the most active compounds separately in the active site of human COX-2 enzyme were also obtained.

引用

页码：718 / 730

页数：13

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