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

doi:10.1016/j.bmcl.2008.07.047

	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-Fan 1; Zhang, Hu-Shan 1; Wang, Yun-Hua 2; Sanchez, Tino 3; Zheng, Yong-Tang 2; Neamati, Nouri 3; Long, Ya-Qiu 1
刊名	BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
	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.