1427579-90-5

Basic information

• Product Name: C₃₆H₂₈N₁₀O₄
• Synonyms: C₃₆H₂₈N₁₀O₄
• CAS NO: 1427579-90-5
• Molecular Weight: 664.683
• Mol File: 1427579-90-5.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: C₃₆H₂₈N₁₀O₄(CAS DataBase Reference)
• NIST Chemistry Reference: C₃₆H₂₈N₁₀O₄(1427579-90-5)
• EPA Substance Registry System: C₃₆H₂₈N₁₀O₄(1427579-90-5)

Safety Data

• Hazardous Substances Data: 1427579-90-5(Hazardous Substances Data)

Upstream product

• 89860-51-5 2-(4-hydroxyphenyl)-4(3H)-quinazolinone 
• 629-13-0 1,2-diazidoethane 
• 1427578-96-8 2-(4-hydroxyphenyl)-3-(prop-2-yn-1-yl)quinazolin-4(3H)-one 
• 28144-70-9 anthranilic acid amide 
• 1427578-84-4 4-(4-oxo-3,4-dihydroquinazolin-2-yl)phenyl acetate 
• 123-08-0 4-hydroxy-benzaldehyde 
• 1427578-89-9 C₁₉H₁₄N₂O₃ 

Relevant articles and documents

Plasmin regulation through allosteric, sulfated, small molecules

Plasmin, a key serine protease, plays a major role in clot lysis and extracellular matrix remodeling. Heparin, a natural polydisperse sulfated glycosaminoglycan, is known to allosterically modulate plasmin activity. No small allosteric inhibitor of plasmin has been discovered to date. We screened an in-house library of 55 sulfated, small glycosaminoglycan mimetics based on nine distinct scaffolds and varying number and positions of sulfate groups to discover several promising hits. Of these, a pentasulfated flavonoid-quinazolinone dimer 32 was found to be the most potent sulfated small inhibitor of plasmin (IC50 = 45 μM, efficacy = 100%). Michaelis-Menten kinetic studies revealed an allosteric inhibition of plasmin by these inhibitors. Studies also indicated that the most potent inhibitors are selective for plasmin over thrombin and factor Xa, two serine proteases in coagulation cascade. Interestingly, different inhibitors exhibited different levels of efficacy (40%-100%), an observation alluding to the unique advantage offered by an allosteric process. Overall, our work presents the first small, synthetic allosteric plasmin inhibitors for further rational design.

Discovery of allosteric modulators of factor XIa by targeting hydrophobic domains adjacent to its heparin-binding site

To discover promising sulfated allosteric modulators (SAMs) of glycosaminoglycan-binding proteins (GBPs), such as human factor XIa (FXIa), we screened a library of 26 synthetic, sulfated quinazolin-4(3H)-ones (QAOs) resulting in the identification of six molecules that reduced the V max of substrate hydrolysis without influencing the KM. Mutagenesis of residues of the heparin-binding site (HBS) of FXIa introduced a nearly 5-fold loss in inhibition potency supporting recognition of an allosteric site. Fluorescence studies showed a sigmoidal binding profile indicating highly cooperative binding. Competition with a positively charged, heparin-binding polymer did not fully nullify inhibition suggesting importance of hydrophobic forces to binding. This discovery suggests the operation of a dual-element recognition process, which relies on an initial Coulombic attraction of anionic SAMs to the cationic HBS of FXIa that forms a locked complex through tight interaction with an adjacent hydrophobic patch. The dual-element strategy may be widely applicable for discovering SAMs of other GBPs.