130420-75-6Relevant academic research and scientific papers
Utilizing Solubility differences to achieve regiocontrol in the synthesis of substituted quinoline-4-carboxylic acids
Lindsay-Scott, Peter J.,Barlow, Helen
supporting information, p. 1516 - 1520 (2016/06/14)
A practical method for the regiocontrolled synthesis of substituted quinoline-4-carboxylic acids is described. Solubility differences between the product quinoline regioisomers enable their facile separation, thus avoiding any challenging chromatographic purifications and allowing access to highly substituted quinoline compounds in three steps from commercially available anilines.
Design of thymidylate synthase inhibitors using protein crystal structures: The synthesis and biological evaluation of a novel class of 5- substituted quinazolinones
Webber,Bleckman,Attard,Deal,Kathardekar,Welsh,Webber,Janson,Matthews,Smith,Freer,Jordan,Bacquet,Howland,Booth,Ward,Hermann,White,Morse,et al.
, p. 733 - 746 (2007/10/02)
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.
