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 LF1; Zhang HS1; Wang YH2; Sanchez T3; Zheng YT2; Neamati N3; Long YQ[*]1 |
| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
 |
| 出版日期 | 2008 |
| 卷号 | 18期号:16页码:4521-4524 |
| ISSN号 | 0960-894X |
| 关键词 | HIV-1 integrase inhibitor bioisostere heteroaromatic carboxylic acid isoxazole isothiazole 1H-pyrazole bioavailability antiviral effect |
| 通讯作者 | yqlong@mail.shcnc.ac.cn |
| 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. |
| 资助信息 | National Natural Science Foundation of China (30672528), Sci- ence and Technology Commission of Shanghai Municipality (07QH14018), Key Scientific and Technological Projects of China (2004BA719A14) and Yunnan province (2004NG12) are greatly appreciated for the financial supports. |
| 收录类别 | SCI |
| 原文出处 | 2008184521.pdf |
| 语种 | 英语 |
| 公开日期 | 2010-08-24 |
| 源URL | [http://159.226.149.42:8088/handle/152453/4629]  |
| 专题 | 昆明动物研究所_分子免疫药理学 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, China 2.Laboratory of Molecular Immunopharmacology, Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China 3.Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90089, USA |
| 推荐引用方式 GB/T 7714 | Zeng LF,Zhang HS,Wang YH,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 LF.,Zhang HS.,Wang YH.,Sanchez T.,Zheng YT.,...&Long YQ[*].(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 LF,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：昆明动物研究所
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