147149-95-9

Upstream product

• 36100-42-2 2-(dimethylamino)-4-nitropyridine N-oxide 
• 52092-43-0 2-bromo-4-nitropyridine N-oxide 
• 147149-94-8 2-(dimethylamino)-4-((4-methoxybenzyl)sulfanyl)pyridine N-oxide 

Relevant academic research and scientific papers

ANTIPROLIFERATIVE QUINAZOLINES

Quinazoline compounds which demonstrate antiproliferative activity, such as antitumor activity, processes of preparing these compounds, pharmaceutical compositions containing these compounds, and the use of these compounds. These compounds inhibit the growth and proliferation of the cells of higher organisms and microorganisms,such as bacteria, yeasts and fungi. Preferred quinazoline compounds are capable of inhibiting the enzyme thymidylate synthase. Effects derived from the inhibition of the enzyme thymidylate synthase include those discussed above

Design of thymidylate synthase inhibitors using protein crystal structures: The synthesis and biological evaluation of a novel class of 5- substituted quinazolinones

The design, synthesis, and biological evaluation of a new class of inhibitors of thymidylate synthase (TS) is described. The molecular design was carried out by a repetitive crystallographic analysis of protein-ligand structures. At the onset of this project, we focused on the folate cofactor binding site of a high-resolution ternary crystal complex of Escherichia coli TS, 5'-fluorodeoxyuridylate (5-FdUMP) and a classical glutamate-containing folic acid analog. A preliminary ternary crystal structure of a novel compound was successfully solved. Upon analysis of this initial complex, further structural elaborations were made, and a series of active 5- (arylthio)quinazolinones was developed. The synthetic strategy was based on the displacement of a halogen at the 5-position of a quinazolinone by various arylthioanions. The compounds were tested for inhibition of purified E. coli and/or human TS, and were assayed for cytotoxicity against three tumor cell lines in vitro. Significant thymidine protection effects were observed with several of the inhibitors, indicating that TS was the intracellular locus of activity.