Prediction of inhibition constants of (R)-3-amidinophenylalanine inhibitors toward factor Xa by 2D-QSAR model

Abstract

A coagulation cascade forms through proteolytic reactions and involves different factors. There are two coagulation pathways, including intrinsic and extrinsic mechanisms, which converge by the formation of factor Xa. Factor Xa plays a crucial role in the formation of the complex with factor Va in the presence of calcium ions and phospholipids. This complex converts prothrombin to thrombin, which leads to the formation of a very strong fibrin clot. Much effort has been devoted to the efficient interference of this enzyme cascade by the inhibition of factor Xa due to its important effect. (R)-3-amidinophenylalanine inhibitors are known inhibitors of factor Xa reported so far. Furthermore, the reliability of the model was also confirmed via statistically significant parameters obtained from validation on an external set.