Drug candidates must undergo thermal evaluation as early as possible in the preclinical phase of drug development because undesirable changes in their structure and physicochemical properties may result in decreased pharmacological activity or enhanced toxicity. Hence, the detailed evaluation of nitrogen-rich heterocyclic esters as potential drug candidates, i.e., imidazolidinoannelated triazinylformic acid ethyl esters 1–3 (where R₁ = 4–CH₃ or 4–OCH₃ or 4–Cl, and R₂ = –COOC₂H₅) and imidazolidinoannelated triazinylacetic acid methyl esters 4–6 (where R₁ = 4–CH₃ or 4–OCH₃ or 4–Cl, and R₂ = –CH₂COOCH₃)—in terms of their melting points, melting enthalpy values, thermal stabilities, pyrolysis, and oxidative decomposition course—has been carried out, using the simultaneous thermal analysis methods (TG/DTG/DSC) coupled with spectroscopic techniques (FTIR and QMS). It was found that the melting process (documented as one sharp peak related to the solid–liquid phase transition) of the investigated esters proceeded without their thermal decomposition. It was confirmed that the melting points of the tested compounds increased in relation to R₁ and R₂ as follows: 2 (R₁ = 4–OCH₃; R₂ = –COOC₂H₅) < 6 (R₁ = 4–Cl; R₂ = –CH₂COOCH₃) < 5 (R₁ = 4–OCH₃; R₂ = –CH₂COOCH₃) < 3 (R₁ = 4–Cl; R₂ = –COOC₂H₅) < 1 (R₁ = 4–CH₃; R₂ = –COOC₂H₅) < 4 (R₁ = 4–CH₃; R₂ = –CH₂COOCH₃). All polynitrogenated heterocyclic esters proved to be thermally stable up to 250 °C in inert and oxidising conditions, although 1–3 were characterised by higher thermal stability compared to 4–6. The results confirmed that both the pyrolysis and the oxidative decomposition of heterocyclic ethyl formates/methyl acetates with para-substitutions at the phenyl moiety proceed according to the radical mechanism. In inert conditions, the pyrolysis process of the studied molecules occurred with the homolytic breaking of the C–C, C–N, and C–O bonds. This led to the emission of alcohol (ethanol in the case of 1–3 or methanol in the case of 4–6), NH₃, HCN, HNCO, aldehydes, CO₂, CH₄, HCl, aromatics, and H₂O. In turn, in the presence of air, cleavage of the C–C, C–N, and C–O bonds connected with some oxidation and combustion processes took place. This led to the emission of the corresponding alcohol depending on the analysed class of heterocyclic esters, NH₃, HCN, HNCO, aldehydes, N₂, NO/NO₂, CO, CO₂, HCl, aromatics, and H₂O. Additionally, after some biological tests, it was proven that all nitrogen-rich heterocyclic esters—as potential drug candidates—are safe for erythrocytes, and some of them are able to protect red blood cells from oxidative stress-induced damage. Full article