A Novel 1,5-Diarylpyrazole Derivative Exerts Its Anti-inflammatory Effect by Inhibition of Cyclooxygenase-2 Activity as a Prodrug
文献类型：期刊论文
| 作者 | Yin, Lin-Lin1; Li, Ming-Hui2; Wang, Xin2 ; Zhang, Wei-Yu2
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| 刊名 | BIOLOGICAL & PHARMACEUTICAL BULLETIN
 |
| 出版日期 | 2009-06 |
| 卷号 | 32期号:6页码:1032-1036 |
| 关键词 | cyclooxygenase-2 inflammation carrageenan-induced paw edema air pouch model prodrug |
| ISSN号 | 0918-6158 |
| DOI | 10.1248/bpb.32.1032 |
| 文献子类 | Article |
| 英文摘要 | In the present study, we designed and synthesized a novel 1,5-diarylpyrazole derivative, 2-amino-N-(2-methyl-5-(1-(4-sulfamoylphenyl)-3-(trifluoromethyl)-1H-pyrazol-5-yl)phenyl) acetamide hydrochloride (CC06), which was intended to act as a prodrug and would exert potent anti-inflammatory activity after being converted to its parent compound in vivo. In vitro cell-based biological assay, CC06 showed decreased inhibitory effects on cyclooxygenase (COX)-1 and COX-2 compared with its parent compounds, but it exhibited potent anti-inflammatory activity in vivo. The anti-inflammatory effect was evaluated in a carrageenan-induced rat paw edema model and CC06 (15, 30, 60 mg/kg, intragastrically) reduced rat paw edema in a dose-dependent manner. CC06 is also a selective inhibitor of COX-2 since it can reduce prostaglandin E-2 (PGE(2)) production in the inflamed pouch dose-dependently without affecting PGE(2) production in stomach in rat air pouch model. Furthermore, preliminary pharmacokinetics experiments were conducted using high performance liquid chromatography/mass spectrometry (HPLU/MS) to detect whether CC06 can convert to its parent compound or not. Our results supported the hypothesis that CC06 was actually converted to its parent compound. These suggested that CC06 served as an anti-inflammatory prodrug and actually converted to its parent compound to exert its anti-inflammatory effect. This finding will be of great benefit in carrying out structural modifications of prodrug-like selective COX-2 inhibitors. |
| WOS关键词 | SELECTIVE-INHIBITION ; MESSENGER-RNA ; CELECOXIB ; INFLAMMATION ; EXPRESSION ; RAT ; PYRAZOLES ; SYNTHASE ; DESIGN ; ENZYME |
| 资助项目 | Ministry of Sciences and Technology of China[2004CB720305] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000266483500013 |
| 出版者 | PHARMACEUTICAL SOC JAPAN |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279221]  |
| 专题 | 信息中心 药物化学研究室 |
| 通讯作者 | Yin, Lin-Lin |
| 作者单位 | 1.Capital Med Univ, Xuanwu Hosp, Dept Pharmacol, Beijing 100053, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Yin, Lin-Lin,Li, Ming-Hui,Wang, Xin,et al. A Novel 1,5-Diarylpyrazole Derivative Exerts Its Anti-inflammatory Effect by Inhibition of Cyclooxygenase-2 Activity as a Prodrug[J]. BIOLOGICAL & PHARMACEUTICAL BULLETIN,2009,32(6):1032-1036. |
| APA | Yin, Lin-Lin,Li, Ming-Hui,Wang, Xin,&Zhang, Wei-Yu.(2009).A Novel 1,5-Diarylpyrazole Derivative Exerts Its Anti-inflammatory Effect by Inhibition of Cyclooxygenase-2 Activity as a Prodrug.BIOLOGICAL & PHARMACEUTICAL BULLETIN,32(6),1032-1036. |
| MLA | Yin, Lin-Lin,et al."A Novel 1,5-Diarylpyrazole Derivative Exerts Its Anti-inflammatory Effect by Inhibition of Cyclooxygenase-2 Activity as a Prodrug".BIOLOGICAL & PHARMACEUTICAL BULLETIN 32.6(2009):1032-1036. |
入库方式： OAI收割
来源：上海药物研究所
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