75896-41-2Relevant academic research and scientific papers
Structure-based drug design of chromone antagonists of the adenosine A 2A receptor
Andrews, Stephen P.,Mason, Jonathan S.,Hurrell, Edward,Congreve, Miles
, p. 571 - 575 (2014)
The structure-guided optimisation of a hit series of chromone derivatives, previously identified using virtual screening of homology models of the adenosine A2A receptor, has led to the discovery of potent, selective and ligand efficient antagonists. Lipophilic hotspots and calculated water networks were modelled within the receptor binding site to facilitate rational ligand design. This journal is the Partner Organisations 2014.
X-Ray Crystallography and Free Energy Calculations Reveal the Binding Mechanism of A2A Adenosine Receptor Antagonists
?qvist, Johan,Azuaje, Jhonny,Congreve, Miles,Cooke, Robert M.,Deflorian, Francesca,Doré, Andrew S.,García-Mera, Xerardo,Gutiérrez-de-Terán, Hugo,Jespers, Willem,Ker?nen, Henrik,Majellaro, Maria,Mason, Jonathan S.,Sotelo, Eddy,Verdon, Grégory,Zhukov, Andrei,de Graaf, Chris
supporting information, p. 16536 - 16543 (2020/07/27)
We present a robust protocol based on iterations of free energy perturbation (FEP) calculations, chemical synthesis, biophysical mapping and X-ray crystallography to reveal the binding mode of an antagonist series to the A2A adenosine receptor (AR). Eight A2AAR binding site mutations from biophysical mapping experiments were initially analyzed with sidechain FEP simulations, performed on alternate binding modes. The results distinctively supported one binding mode, which was subsequently used to design new chromone derivatives. Their affinities for the A2AAR were experimentally determined and investigated through a cycle of ligand-FEP calculations, validating the binding orientation of the different chemical substituents proposed. Subsequent X-ray crystallography of the A2AAR with a low and a high affinity chromone derivative confirmed the predicted binding orientation. The new molecules and structures here reported were driven by free energy calculations, and provide new insights on antagonist binding to the A2AAR, an emerging target in immuno-oncology.
CHEMISTRY OF MODIFIED FLAVONOIDS. XVIII. THIAZOLE ANALOGS OF ISOFLAVONES. HOMOLOGOUS AND ISOMERIC SERIES
Gorbulenko, N. V.,Turov, A. V.,Khilya, V. P.
, p. 441 - 448 (2007/10/03)
Homologous and isomeric series of thiazole derivatives of isoflavones were produced on the basis of α-(4-methyl-2-thiazolyl)-2-hydroxyacetophenones.A study of α-(4-methyl-2-thiazolyl)-2-hydroxyacetophenones by PMR spectroscopy showed that these compounds exist in most nonpolar and low-polarity organic solvents exclusively in the ketone form, but in dimethyl sulfoxide solution both the ketone and enol forms are observed in various ratios.A simple and effective preparative method of synthesis of homologs of 3-(2-diazolyl)chromones was developed, and their alkylationat the phenolic hydroxyl was studied.Data of biological tests of the compounds synthesized are presented.
