QSAR study of 2,4-dihydro-3H-1,2,4-triazol-3-ones derivatives as angiotensin II AT1 receptor antagonists based on the Monte Carlo method

Abstract

The Monte Carlo method was used for QSAR modelling 2,4-dihydro-3H-1,2,4-triazol-3-ones derivatives as angiotensin II AT1 receptor antagonists. QSAR models were calculated with the representation of the molecular structure by the simplified molecular input-line entry system (SMILES) and with optimal molecular descriptors based on the SMILES notation and local graph invariants. One random split into the training and the test set was used. The statistical quality of the developed model was good. The best calculated QSAR model had the following statistical parameters: r 2 = 0.8701 for the training set and r 2 = 0.8430 for the test set. Novel statistical metric entitled as the index of ideality of correlation was used for final model assessment, and the obtained results were good. Structural indicators defined as molecular fragments responsible for increases and decreases of the studied activity were calculated. The computer-aided design of new compounds as potential angiotensin II AT1 receptor antagonists with the application of defined structural alerts was presented.