QSAR and Molecular Modeling Studiesof Factor Xa and Thrombin Inhibitors

  • Dimitra Hadjipavlou-LitinaEmail author
Part of the Topics in Heterocyclic Chemistry book series (TOPICS, volume 4)


Thrombotic disorders remain the major cause of death and disability in Western society. Many approaches to develop antithrombotic drugs that interfere with enzymes in the coagulation system have been pursued over the past few decades. Factor FXa and thrombin are both bound to and are enzymatically active in blood clots. In this article, a brief review is presented on the QSAR and molecular modelling studies on FXa and thrombin inhibitors reported during the last decade. The results from the widely used CoMFA and CoMSIA methods have been included. Analogues with various heterocyclic rings, isoquinoline derivatives, five- or six-membered heteroaryl derivatives, benzoxazinones, and tetrazoles are included in the discussion. Hydrophobic property of molecules is shown to play a significant role. In most of the cases, CMR/MR as well as Sterimol parameters have been shown to be important. Electronic factors, with the exception of the Hammett's constant, have not been found to be of much importance.

Serine proteases Thrombin and Factor FXa QSAR Molecular modeling Heterocycles 



Adaptation of fields for molecular comparison




Average of absolute values of residuals

C log P

Lipophilicity values calculated theoretically according to Hansch and Leo


Comparative molecular similarity index analysis


Comparative molecular field analysis


Comparative binding energy


Degrees of freedom


Free energy related


Low molecular weight heparins


Genetic algorithm multiple linear regression


Multiple linear regression


Partial least squares


Protein data bank


Quantitative structure activity relationships


Quantitative structure property relationships


Sum of the squared errors of prediction


Adjusted correlation coefficient


Bootstrapped correlation coefficient




Root mean square


Root mean square error


Standard deviation sum of the squared errors of prediction


Standard deviation sum of the error of prediction


Program for the estimation of logP using the atom – weighted solvent accessible surface areas


Tissue-type plasminogen activator


Tailored scored function


Urokinase-type plasminogen activator


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Authors and Affiliations

  1. 1.Department of Pharmaceutical Chemistry, School of PharmacyAristotle University of ThessalonikiThessalonikiGreece

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