Title of article :
2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: a novel class of small molecule heparanase inhibitors
Author/Authors :
Stephen M. Courtney، نويسنده , , Philip A. Hay، نويسنده , , Richard T. Buck، نويسنده , , Claire S. Colville، نويسنده , , David W. Porter، نويسنده , , David I.C. Scopes، نويسنده , , Faye C. Pollard، نويسنده , , Martin J. Page، نويسنده , , James M. Bennett، نويسنده , , Margaret L. Hircock، نويسنده , , Edward A. McKenzie، نويسنده , , Colin R. Stubberfield، نويسنده , , Paul R. Turner، نويسنده ,
Abstract :
A novel class of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acids are described as inhibitors of the endo-β-glucuronidase heparanase. Several of the compounds, for example, 2-[4-propylamino-5-[5-(4-chloro)phenyl-benzoxazol-2-yl]phenyl]-2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid (9c), display potent heparanase inhibitory activity (IC50 200–500 nM) and have high selectivity (>100-fold) over human β-glucuronidase. They also show anti-angiogenic effects. Such compounds should serve as useful biological tools and may provide a basis for the design of novel therapeutic agents.
Keywords :
heparanase , angiogenesis , metastasis , Isoindole-5-carboxylic acid. , b-glucuronidase
