ICCAS OpenIR
Discovery of Dual Target Inhibitors against Cyclooxygenases and Leukotriene A(4) Hydrolyase
Chen, Zheng; Wu, Yiran; Liu, Ying; Yang, Suijia; Chen, Yunjie; Lai, Luhua
2011-05-26
Source PublicationJOURNAL OF MEDICINAL CHEMISTRY
ISSN0022-2623
Volume54Issue:10Pages:3650-3660
AbstractDual target inhibitors against COX-2. and LTA(4)H were designed by adding functional groups from a marketed COX-2 inhibitor, Nimesulide, to an existing LTA(4)H inhibitor 1-(2-(4-phenoxyphenoxy) ethyl) pyrrolidine. A series of phenoxyphenyl pyrrolidine compounds were synthesized and tested for their inhibition activities using enzyme assays and human whole blood assay. Introduction of small electron withdrawing groups like NO2 and CF3 in the ortho-position of the terminal phenyl ring was found to change the original single target LTA(4)H inhibitor to dual target LTA(4)H and COX-2 inhibitors. Compound 5a and 5m showed dual LTA(4)H and COX-2 inhibition activities in the enzyme assays and the I-EWE assay with IC50 values in the micromolar to submicromolar range. As their activities in HWB assay were comparable to the two starting single target inhibitors, the two compounds are promising for further studies. The strategy used in the current study may be generally applicable to other dual target drug designs.
DOI10.1021/jm200063s
Indexed BySCI ; IC
Language英语
WOS IDWOS:000290651800015
PublisherAMER CHEMICAL SOC
Citation statistics
Cited Times:34[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.iccas.ac.cn/handle/121111/72626
Collection中国科学院化学研究所
Corresponding AuthorLiu, Ying
AffiliationPeking Univ, Coll Chem & Mol Engn, State Key Lab Struct Chem Unstable & Stable Speci, BNLMS, Beijing 100871, Peoples R China
Recommended Citation
GB/T 7714
Chen, Zheng,Wu, Yiran,Liu, Ying,et al. Discovery of Dual Target Inhibitors against Cyclooxygenases and Leukotriene A(4) Hydrolyase[J]. JOURNAL OF MEDICINAL CHEMISTRY,2011,54(10):3650-3660.
APA Chen, Zheng,Wu, Yiran,Liu, Ying,Yang, Suijia,Chen, Yunjie,&Lai, Luhua.(2011).Discovery of Dual Target Inhibitors against Cyclooxygenases and Leukotriene A(4) Hydrolyase.JOURNAL OF MEDICINAL CHEMISTRY,54(10),3650-3660.
MLA Chen, Zheng,et al."Discovery of Dual Target Inhibitors against Cyclooxygenases and Leukotriene A(4) Hydrolyase".JOURNAL OF MEDICINAL CHEMISTRY 54.10(2011):3650-3660.
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