Quantitative Structure–Activity Relationship and Combinatorial Design of 1,3,4-Oxadiazole-Based Thymidine Phosphorylase Inhibitors as Potential Anti-Cancer Agents

The 3D quantitative structure–activity relationship model representing r² = 0.8605, q² = 0.8193 and pred_r² = 0.6847 respectively, was generated for thymidine phosphorylase (TP) inhibitory activity of some 1,3,4-oxadiazole derivatives. Electronegative substituents at R¹ and less steric bulk with electropositive substituents at R² were found to be favourable for TP inhibition. The activity prediction of a combinatorial library of 1629 compounds resulted in 50 molecules whose predicted activity was comparable to the most active compound in the dataset and within the model’s applicability domain. Among them six molecules showed favourable interactions with the active site of TP proposing potential anticancer activity of the title compounds.