A Facile Hydroxyindole Carboxylic Acid Based Focused Library Approach for Potent and Selective Inhibitors of Mycobacterium Protein Tyrosine Phosphatase B. Issue 6 (8th April 2013)

• Record Type: Journal Article
• Authors: Zeng, Li‐Fan; Xu, Jie; He, Yantao; He, Rongjun; Wu, Li; Gunawan, Andrea M.; Zhang, Zhong‐Yin
• Is Part Of: ChemMedChem. Volume 8:Issue 6(2013:Jun.)
• Page Start: 904
• Page End: 908
• Publication Date: 2013-04-08
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201300115
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="graphical" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <bold>Focused on</bold> <italic> <bold>Mtb</bold> </italic> <bold>:</bold> A facile hydroxyindole carboxylic acid based focused amide library was designed to target both the PTP active site and a unique nearby pocket for enhanced affinity and selectivity. HTS of the library led to the identification of a highly potent and selective inhibitor, <bold>11 a</bold>, of mPTPB, an essential virulence factor for <italic>Mycobacterium tuberculosis.</italic> Compound <bold>11 a</bold> shows high cellular activity and is capable of reversing the altered immune responses induced by mPTPB in macrophages.<boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg21cjs1zv" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>