Title of article :
Structure-based design, synthesis, and SAR evaluation of a new series of 8-hydroxyquinolines as HIF-1α prolyl hydroxylase inhibitors
Author/Authors :
Namal C. Warshakoon، نويسنده , , Shengde Wu، نويسنده , , Angelique Boyer، نويسنده , , Richard Kawamoto، نويسنده , , Justin Sheville، نويسنده , , Sean Renock، نويسنده , , Kevin Xu، نويسنده , , Matthew Pokross، نويسنده , , Songtao Zhou، نويسنده , , Carol Winter، نويسنده , , Richard Walter، نويسنده , , Marlene Mekel، نويسنده , , Artem G. Evdokimov، نويسنده ,
Abstract :
A new series of potent 8-hydroxyquinolines was designed based on the newly resolved X-ray crystal structure of EGLN-1. Both alkyl and aryl 8-hydroxyquinoline-7-carboxyamides were good HIF-1α prolyl hydroxylase (EGLN) inhibitors. In subsequent VEGF induction assays, these exhibited potent VEGF activity. In addition, this class of compounds did show the ability to stabilize HIF-1α.
Keywords :
Prolyl hydroxylase inhibitors , HIF-1? , Peripheral arterial disease (PAD) , ischemia , 8-Hydroxyquinolinecarboxyamides , anemia , hypoxia
