Discovery of novel, potent, selective and cellular active ADC type PTP1B inhibitors via fragment-docking-oriented de novel design. Issue 15 (1st August 2015)

• Record Type: Journal Article
• Authors: Du, Yongli; Ling, Hao; zhang, Meng; Shen, Jingkang; Li, Qunyi
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 15(2015)
• Page Start: 4891
• Page End: 4898
• Publication Date: 2015-08-01
• Subjects: KOBGHKYLTVSLKX-UHFFFAOYSA-N -- ADBBUKZUEBEVEK-UHFFFAOYSA-N -- SJNOIBCXURLNBQ-UHFFFAOYSA-N -- HKZLUCVFMYQMDK-UHFFFAOYSA-N -- WBRMRRZOXGTVRG-UHFFFAOYSA-N -- MXLLZUGZFRWOMO-UHFFFAOYSA-N -- QSHDKOQYBLMLQD-UHFFFAOYSA-N; Protein tyrosine phosphatase 1B inhibitor -- N-(2, 5-Diethoxy-phenyl)-methanesulfonamide -- Type 2 diabetes mellitus -- Insulin signaling; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.05.032
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.