Efficient synthesis and utilization of phenyl-substituted heteroaromatic carboxylic acids as aryl diketo acid isosteres in the design of novel HIV-1 integrase inhibitors

	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 LF 1; Zhang HS 1; Wang YH 2; Sanchez T 3; Zheng YT 2; Neamati N 3; Long YQ*1; yqlong@mail.shcnc.ac.cn
	2008
发表期刊	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN	0960-894X
卷号	18 期号:16 页码:4521-4524
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.
关键词	Hiv-1 Integrase Inhibitor Bioisostere Heteroaromatic Carboxylic Acid Isoxazole Isothiazole 1h-pyrazole Bioavailability Antiviral Effect
资助者	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. ; 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. ; 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. ; 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.
URL	查看原文
收录类别	SCI
语种	英语
资助者	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. ; 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. ; 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. ; 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.
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/4629
专题	科研部门_分子免疫药理学（郑永唐）科研部门_动物模型与人类重大疾病机理重点实验室
通讯作者	yqlong@mail.shcnc.ac.cn
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.,...&yqlong@mail.shcnc.ac.cn.(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.

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2008184521.pdf（267KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文