1155268-91-9

Upstream product

• 1431939-94-4 4-(piperazin-1-yl)-2-(pyridin-2-yl)-quinazoline 
• 98-59-9 p-toluenesulfonyl chloride 
• 91748-47-9 4-Chloro-2-(pyridin-2-yl)-quinazoline 
• 118-92-3 anthranilic acid 
• 100-70-9 2-Cyanopyridine 
• 28594-60-7 2-(2-pyridyl)-2,3-dihydroquinazolin-4-(1H)-one 

Relevant academic research and scientific papers

Pyridinylquinazolines selectively inhibit human methionine aminopeptidase-1 in cells

Methionine aminopeptidases (MetAPs), which remove the initiator methionine from nascent peptides, are essential in all organisms. While MetAP2 has been demonstrated to be a therapeutic target for inhibiting angiogenesis in mammals, MetAP1 seems to be vital for cell proliferation. Our earlier efforts identified two structural classes of human MetAP1 (HsMetAP1)-selective inhibitors (1-4), but all of them failed to inhibit cellular HsMetAP1. Using Mn(II) or Zn(II) to activate HsMetAP1, we found that 1-4 could only effectively inhibit purified HsMetAP1 in the presence of physiologically unachievable concentrations of Co(II). In an effort to seek Co(II)-independent inhibitors, a novel structural class containing a 2-(pyridin-2-yl)quinazoline core has been discovered. Many compounds in this class potently and selectively inhibited HsMetAP1 without Co(II). Subsequently, we demonstrated that 11j, an auxiliary metal-dependent inhibitor, effectively inhibited HsMetAP1 in primary cells. This is the first report that an HsMetAP1-selective inhibitor is effective against its target in cells.

INHIBITORS OF HUMAN METHIONINE AMINOPEPTIDASE 1 AND METHODS OF TREATING DISORDERS

Described herein are novel pyrimidine-pyridine compounds, methods of inhibiting methionine aminopeptidase and treating disorders (or symptoms thereof) associated with methionine aminopeptidase, wherein a compound of the invention is administered to a subject.