Author/Authors :
Zhili Xin، نويسنده , , Thorsten K. Oost، نويسنده , , Cele Abad-Zapatero، نويسنده , , Philip J. Hajduk، نويسنده , , Zhonghua Pei، نويسنده , , Bruce G. Szczepankiewicz، نويسنده , , Charles W. Hutchins، نويسنده , , Steve J. Ballaron، نويسنده , , Mike A. Stashko، نويسنده , , Tom Lubben، نويسنده , , James M. Trevillyan، نويسنده , , Mike R. Jirousek، نويسنده , , Gang Liu، نويسنده ,
Abstract :
We have previously reported a novel series of oxalyl-aryl-amino benzoic acid-based, catalytic site-directed, competitive, reversible protein tyrosine phosphatase 1B (PTP1B) inhibitors. With readily access to key intermediates, we utilized a solution phase parallel synthesis approach and rapidly identified a highly potent PTP1B inhibitor (19, Ki=76 nM) with moderate selectivity (5-fold) over T-cell PTPase (TCPTP) through interacting with a second phosphotyrosine binding site (site 2) in the close proximity to the catalytic site.
