¹Computational Chemistry Research Lab., Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur (MS) India DOI : 10.12991/marupj.323292 Factor Xa (FXa), a trypsin-like serine protease, is wellestablished target for the development of the anticoagulants. Number of molecules were reported as Factor Xa inhibitors but most of them have pharmacokinetic issues. In this present communication, we report development and validation of the group based quantitative structure activity relationship (GQSAR) studies on 48 chromen-2-one derivatives as effective inhibitors of FXa. All the molecules were fragmented into eleven functional fragments (R1, R2, R3, R4, R5, R6, R7, R8, R9, R10 and R11). All the developed GQSAR models were generated using multiple linear regression analysis (MLR). The generated GQSAR models were selected on the basis of statistical data that models having r² should be above 0.6 were used to check the external predictivity while the significance of the model was decided on the basis of F value. Developed GQSAR models reveled presence of lipophilic groups on fragment R6 will diminish the bio-activity while at R2 it will lead to increase in bioactivity of molecules. Additionally, minimum number of rotatable bonds at fragments R1 was fruitful for better FXa inhibition activity. The results of GQSAR models may lead to better understanding of design and development of novel FXa inhibitors. Keywords : FXa, Vlife MDS, Anticoagulant, Quantitative Structure Activity Relationship, GQSAR, Slogp