Combined in silico strategy for molecular mechanisms exploration of a series 3H-thiazolo[4,5-b]pyridin-2-ones exhibiting strong anti-exudative action through QSAR analysis, molecular docking and pharmacophore modelling is reported. GA-ML technique was used for QSAR models generation with 2D autocorrelation descriptors. One- and two-parameter regressions revealed that certain structural patterns or heteroatoms contribute mutually to the anti-exudative activity potentiation. Possible action mechanisms were discovered through flexible docking simulations with cyclooxygenase pathway enzymes (COX-1, COX-2, mPGES-1). Docking results indicated the possibility of stable complexes formation with the effective docking scores and proper orientation of ligands within the enzymes active sites. Pharmacophore modelling was carried out using protein-ligand interaction fingerprints methodology. Two- and three-centre 3D pharmacophore queries were constructed. Their analysis indicated the functionality of bicyclic thiazolopyridine scaffold proved by the steric placement of heteroatoms in the corresponding pharmacophore centres.

A quantitative structure-activity relationship (QSAR) study has been carried out for 32 N³ substituted 3H-thiazolo[4,5-b]pyridin-2-onederivatives as potential antioxidant drug candidates. The genetic algorithm (GA) and multiple linear regression analysis (MLRA) were used as appropriate techniques for descriptor selection and correlation model generation. The four best regressions for predicting the ability to scavenge the DPPH radical were generated as three-parameter QSAR models with the highest statistical characteristics and predictive power. It was shown that a set of 2D, 3D, and Molecular properties descriptors play a crucial role in antioxidant activity enhancement. Small hydrophilic molecules with the minimal distance of specific atoms and fragments from the center of mass, neglectable electronic density redistribution between the distant atoms, and molecules keeping strong symmetry of electronegative atoms along the 1^st principal component axe exhibit higher activity. Validation parameters of the generated models allow us to state that they satisfy the statistical requirements for their goodness-of-fitting with no current overfitting. The predictive ability of the constructed models was assessed with both internal and external validation approaches and estimated with the leave-one-out and leave-group-out cross-validation coefficients (Q²_LOO and Q²_LGO). The values of Q²_LOO (0.7060 ¸ 0.7480) and Q²_LGO (0.6647 ¸ 0.7711) are reasonable, showing that the models are significant and robust to predict the free radical scavenging activity of the compounds from both training and validation sets. Applicability domain-defining technique was employed in the obtained models, and indicated that most structures were adequately represented by the chemical space of the models.

The present microreview systematizes recent advances in the synthetic approaches for novel thiazolo[4,5-b]-pyridines and summarizes pharmacological effects they were found to possess. In particular, modern synthetic techniques for thiazolo[4,5-b]pyridine bicyclic scaffold construction starting from thiazole or thiazolidine derivatives followed by pyridine annulation, which results in the target fused thiazolo[4,5-b]pyridines, are analyzed.

УДК: 616–093+547.789

The present microreview provides access to recent advances in the synthetic approaches to novel thiazolo[4,5-b]-pyridines developed over the last years. This second part presents the overview and analysis of modern synthetic techniques for thiazolo[4,5-b]pyridine bicyclic scaffold construction starting from pyridine derivatives followed by thiazole heterocycle annulation

УДК: 616–093+547.789

As a result of the furfural reaction with diazonium, salts 1a-h the arylfuran-2-carbaldehydes 3a-h were synthesized. In the reaction of Wilgerodt-Kindler, arylfuran-2-carbaldehydes with sulfur and aryl piperazines was prepared 1-aryl-4-[(5-aryl-2-furyl)carbonothioyl]piperazines. The structures of target compounds 5a-l were confirmed by using 1H NMR spectroscopy and elemental analysis. The antimicrobial activity of the synthesized substances was evaluated by the value of the MIC and minimum fungicidal and bactericidal concentration. The findings exhibited that the compounds
possessed moderate antimicrobial potential. In vitro anticancer activity assessment on the full panel