QSAR Analysis on 3,4-disubstituted-1H-pyrazol-5(4H)-ones as KDR/VEGFR- 2 kinase inhibitors

Quantitative structure activity relationship (QSAR) study was performed on a series of 3,4-disubstituted-1Hpyrazol- 5(4H)-ones possessing KDR/VEGFR-2 kinase inhibitory activity for establishing quantitative relationship between biological activity and their physicochemical/ structural properties. Several statistical regression expressions were obtained using partial least squares regression (PLSR) analysis. Most statistical significant model generated, explains 80% (r2 = 0.8044) of the total variance in the training set and has an internal (q2) and external (pred_r2) predictive ability of ~71% (q2 = 0.7077) and ~90% (pred_r2 = 0.8959). In this model the positive coefficient value of T_T_N_7 [This is the count of number of any atoms separated from any Nitrogen atom (single, double or triple bonded) by 7 bond distance in a molecule] and T_N_Br_4 [this is the count of number of Nitrogen atoms (single, double or triple bonded) separated from any Bromine atom by 4 bonds in a molecule] on the biological activity indicated that higher value leads to better KDR/VEGFR-2 kinase inhibitory activity whereas lower value leads to decrease activity. Negative coefficient value of T_C_N_3 [This is the count of number of Carbon atoms (single, double or triple bonded) separated from any Nitrogen atom (single, double or triple bonded) by 3 bond distance in a molecule] and AveragePotential on the biological activity indicated that lower values leads to good KDR/VEGFR-2 kinase inhibitory activity while higher value leads to reduced activity. Contribution chart reveals that the descriptors T_T_N_7, T_C_N_3, AveragePotential and T_N_Br_4 contributing 22.56%, 34.34%, 24.87% and 18.22 % respectively.