Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors | |
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
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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. |
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关键词 | RECEPTOR |
WOS研究方向 | Pharmacology & Pharmacy ; Chemistry |
语种 | 英语 |
出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
WOS记录号 | WOS:000258769200014 |
内容类型 | 期刊论文 |
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. |
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