Synthesis and in-Silico Studies of Some New Thiazole Carboxamide Derivatives with Theoretical Investigation

Based on the tremendous pharmacological activities of compounds containing thiazole and carboxamide moieties, the current study aims to prepare new series of thiazole, pyrazole, pyridine, and thiophene derivatives incorporating thiazole carboxamide moiety. Construction of the target compounds was achieved via different chemical transformations and using easily accessible starting materials. The structures of the synthesized compounds were confirmed by all possible spectral and elemental analyses. Results from the in-silico studies showed different Lipophilicity (log p) and Number of Lipinsk’s violations due to the presence of NH₂, C≡N, OH, and C=O groups which make more electrostatic hydrogen bond interactions in compounds 17 and 20 which increase their TPSA (Å2). These results were confirmed through docking simulation with PDBID: 5I9I which showed the least binding affinity with different proteins, and optimization of these heterocyclic compounds with computational calculations and identification of their physical descriptors which showed more stabilities and directed us for biological evaluation for further studies.