Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors
文献类型：期刊论文
| 作者 | Zeng, Li-Fan1; Zhang, Hu-Shan1; Wang, Yun-Hua2; Sanchez, Tino3; Zheng, Yong-Tang2; Neamati, Nouri3; Long, Ya-Qiu1 |
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2008-08-15 |
| 卷号 | 18期号:16页码:4521-4524 |
| 关键词 | HIV-1 integrase inhibitor bioisostere heteroaromatic carboxylic acid isoxazole isothiazole 1H-pyrazole bioavailability antiviral effect |
| ISSN号 | 0960-894X |
| DOI | 10.1016/j.bmcl.2008.07.047 |
| 文献子类 | Article |
| 英文摘要 | Three new types of aryl diketo acid (ADK) isosteres were designed by conversion of the biologically labile 1,3-diketo unit into heteroaromatic motif such as isoxazole, isothiazole, or 1H-pyrazole to improve the physicochemical property of ADK-based HIV-1 integrase (IN) inhibitors. The synthesis of the heteroaromatic carboxylic acids was established by employing phenyl beta-diketoester or benzaldehyde as the starting material and 1,3-dipolar cycloaddition as the key reaction. Of the compounds tested, the 3-benzyloxyphenyl-substituted isoxazole carboxylic acid displayed the best IN inhibitory and antiviral activities, with N-hydroxylamidation enhancing the in vitro and in vivo potency. These findings are important for further optimization of ADK-based IN inhibitors. (c) 2008 Elsevier Ltd. All rights reserved. |
| WOS关键词 | RECEPTOR |
| 资助项目 | National Natural Science Foundation of China[30672528] ; Science and Technology Commission of Shanghai Municipality[07QH14018] ; Key Scientific and Technological Projects of China[200413A719A14] ; Yunnan province[2004NG12] |
| WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000258769200014 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/272835]  |
| 专题 | 药物化学研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Long, Ya-Qiu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Materia Med, State Key Lab Drug Research, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mech, Lab Mol Immunopharmacol, Kunming 650223, Peoples R China; 3.Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA |
| 推荐引用方式 GB/T 7714 | Zeng, Li-Fan,Zhang, Hu-Shan,Wang, Yun-Hua,et al. Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,2008,18(16):4521-4524. |
| APA | Zeng, Li-Fan.,Zhang, Hu-Shan.,Wang, Yun-Hua.,Sanchez, Tino.,Zheng, Yong-Tang.,...&Long, Ya-Qiu.(2008).Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors.BIOORGANIC & MEDICINAL CHEMISTRY LETTERS,18(16),4521-4524. |
| MLA | Zeng, Li-Fan,et al."Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors".BIOORGANIC & MEDICINAL CHEMISTRY LETTERS 18.16(2008):4521-4524. |
入库方式： OAI收割
来源：上海药物研究所
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