Discovery of novel, potent, selective and cellular active ADC type PTP1B inhibitors via fragment-docking-oriented de
Yongli Du1, Hao Ling1, Meng Zhang2
1School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, 3501 Daxue Road, Jinan 250353, China.
Bioorganic & Medicinal Chemistry
|June 24, 2015
Abstract:
Fragment-docking-oriented de novel design for both the catalytic site and the C phosphotyrosine binding site led to the discovery of novel scaffold and chemical easy N-(2,5-diethoxy-phenyl)-methanesulfonamide based phosphotyrosine mimetics that when incorporated into ureas are high potent and selective inhibitors of protein tyrosine phosphatase 1B. Among them, compound 15 was shown to be the most potent PTP1B inhibitor with great selectivity over the highly homologous T-cell protein tyrosine phosphatase.
