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Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B
Li Hui 1 #,Zou-Hui 2,Gao Lixin 3,Liu Ting 4,Yang Fan 5,Li Jingya 3,Li Jia 3,Qiu Wen-Wei 2 * #,Tang Jie 4
1.Shanghai Engineering Research Center of Molecular Theraputics and New Drug Development, East China Normal University, ShangHai 200062
2.Department of Chemistry, East China Normal University, Shanghai 200062
3.National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institute for Biological Science, Chinese Academy of Science, Shanghai 201203
4.Shanghai Engineering Research Center of Molecular Theraputics and New Drug Development, East China Normal University, Shanghai 200062
5. Shanghai Engineering Research Center of Molecular Theraputics and New Drug Development, East China Normal University, Shanghai 200062
*Correspondence author
#Submitted by
Subject:
Funding: National Natural Science Foundation of China (No.NO. 20802020), Ph.D. Program Foundation of Ministry of Education of China (No.No. 20080269103)
Opened online:13 February 2012
Accepted by: none
Citation: Li Hui,Zou-Hui,Gao Lixin.Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Novel Inhibitors of Protein Tyrosine Phosphatase 1B[OL]. [13 February 2012] http://en.paper.edu.cn/en_releasepaper/content/4463053
 
 
A series of oleanolic acid (OA) derivatives have been synthesized and their inhibitory effects on PTP1B, TCPTP and related PTPs are evaluated. Some compounds with five-membered heterocyclic ring fused at C-2, C-3 positions showed a dramatic increase in inhibition, the two most potent PTP1B inhibitors 19 (IC50 = 0.91 μM) and 21 (IC50 = 0.98 μM) showed about 3-fold more potent than lead compound OA. Some compounds with C-ring modified showed high selectivity for PTP1B over TCPTP, among them, 50 possessed the best selectivity of 6.6-fold.
Keywords:oleanolic acid derivatives; PTP1B; inhibition
 
 
 

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