Abstract
Objective: The main objective of the present study was to evolve a novel pharmacophore of methaniminium derivatives as factor Xa inhibitors by developing best 2D and 3D QSAR models.
 The models were developed for amino (3-((3, 5-difluoro-4-methyl-6-phenoxypyridine-2-yl) oxy) phenyl) methaniminium derivatives as factor Xa inhibitors.
 Methods: With the help of Marvin application, 2D structures of thirty compounds of methaniminium derivatives were drawn and consequently converted to 3D structures. 2D QSAR using multiple linear regression (MLR) analysis and PLS regression method was performed with the help of molecular design suite VLife MDS 4.3.3. 3D QSAR analysis was carried out using k-Nearest Neighbour Molecular Field Analysis (k-NN-MFA).
 Results: The most significant 2D models of methaniminium derivatives calculated squared correlation coefficient value 0.8002 using multiple linear regression (MLR) analysis. Partial Least Square (PLS) regression method was also employed. The results of both the methods were compared. In 2D QSAR model, T_C_O_5, T_2_O_2, s log p, T_2_O_1 and T_2_O_6 descriptors were found significant.
 The best 3D QSAR model with k-Nearest Neighbour Molecular Field Analysis have predicted q2 value 0.8790, q2_se value 0.0794, pred r2 value 0.9340 and pred_r2 se value 0.0540. The stepwise regression method was employed for anticipating the inhibitory activity of this class of compound. The 3D model demonstrated that hydrophobic, electrostatic and steric descriptors exhibit a crucial role in determining the inhibitory activity of this class of compounds.
 Conclusion: The developed 2D and 3D QSAR models have shown good r2 and q2 values of 0.8002 and 0.8790 respectively. There is high agreement in inhibitory properties of experimental and predicted values, which suggests that derived QSAR models have good predicting properties.
 The contour plots of 3D QSAR (k-NN-MFA) method furnish additional information on the relationship between the structure of the compound and their inhibitory activities which can be employed to construct newer potent factor Xa inhibitors.
Highlights
The structure of any molecule dictates its properties
There is high agreement in inhibitory properties of experimental and predicted values, which suggests that derived QSAR models have good predicting properties
The 3D model revealed that hydrophobic, electrostatic and steric descriptors exhibit a critical role in determining the inhibitory activity of this class of compounds
Summary
The structure of any molecule dictates its properties. By modifying the chemical structure of any compound, its biological activities get changed. The biological activity of a compound is a function of its chemical structure. QSAR suggests that if a group of chemicals show the same mechanism of action towards a target alteration in the biological activity alters chemical, structural and physical properties [1]. QSAR methods are used in drug designing but are widely used in other sciences too, i.e. in biology, toxicology [2,3]. Environmental toxicology [4], agrochemistry, pharmaceutical chemistry etc. The QSAR is used to determine the initial and final point of synthesis [5]. This, in turn, reduces the number of compounds that could be practically/experimentally synthesized
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