Abstract

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.

摘要

基于含有噻唑和甲酰胺基团的化合物的巨大药理活性，本研究旨在制备新系列含有噻唑甲酰胺基团的噻唑、吡唑、吡啶和噻吩衍生物。目标化合物的构建是通过不同的化学转化并使用易于获得的起始材料来实现的。合成化合物的结构通过所有可能的光谱和元素分析得到证实。计算机研究结果显示，由于 NH _{2 、CeqN、OH 和 C=O 基团的存在，化合物}17和20中存在更多静电氢键相互作用，因此显示出不同的亲脂性 (log p) 和 Lipinsk 违规数从而增加其 TPSA (Å2)。这些结果通过与 PDBID: 5I9I 的对接模拟得到证实，PDBID: 5I9I 显示出与不同蛋白质的最小结合亲和力，并通过计算计算优化这些杂环化合物并鉴定其物理描述符，显示出更高的稳定性，并指导我们进行进一步研究的生物学评估。