Identification and initial structure-activity relationships of a novel class of nonpeptide inhibitors of blood coagulation factor Xa
The discovery and some of the basic structure-activity relationships of a series of novel nonpeptide inhibitors of blood coagulation Factor Xa is described. These inhibitors are functionalized β-alanines, exemplified by 2a. Docking experiments placing 2a in the active site of Factor Xa implied that the most expeditious route to enhancing in vitro potency was to modify the group occupying the S3 site of the enzyme. Increasing the hydrophobic contacts between the inhibitor and the enzyme in this region led to 8, which has served as the prototype for this series. In addition, an enantioselective synthesis of these substituted β-alanines was also developed.
Klein, Scott I.,Czekaj, Mark,Gardner, Charles J.,Guertin, Kevin R.,Cheney, Daniel L.,Spada, Alfred P.,Bolton, Scott A.,Brown, Karen,Colussi, Dennis,Heran, Christopher L.,Morgan, Suzanne R.,Leadley, Robert J.,Dunwiddie, Christopher T.,Perrone, Mark H.,Chu, Valeria
p. 437 - 450
(2007/10/03)
Biphenyl esters and liquid crystalline mixtures comprising them
Biphenyl esters of the formula STR1 wherein X is --CO--O-- or --O--CO-- and R1 and R2 each are alkyl or alkoxy of 1 - 8 carbon atoms, enlarge significantly the temperature range of the nematic phase of liquid-crystalline compositions without adversely affecting other properties.