Abstract

Novel 6-bromo-imidazo[4,5-b]pyridine derivatives (2-4, 5a-13a, and 6b, 8b-13b) have been synthesized based on a developed systematic approach involving the condensation of 5-Bromo-2,3-diaminopyridine with a suitable aromatic aldehyde in the presence of molecular iodine in water, followed by alkylation reactions using different alkyl dibromide agents. The synthesized compounds were characterized by the NMR spectroscopy technique. The structures of 8a, 9a, 12a, and 11b were confirmed using monocrystalline X-ray crystallography. Theoretical calculations have been carried out using DFT and TD-DFT methods at the B3LYP/6-31G++(d,p) level of theory. Intermolecular contacts between units of 8a, 9a, 12a, and 11b were determined through the Hirshfeld surface analysis. The molecular docking study has been performed to determine the binding affinity of 8a, 9a, 12a, and 11b into the binding site of S. aureus tyrosyl-tRNA synthetase as a target enzyme, and the results revealed that 9a is the most potent compound among the selected compounds with a binding affinity of −8.74 Kcal/mol.

Communicated by Ramaswamy H. Sarma

摘要

新型 6-溴-咪唑并 [4,5-b] 吡啶衍生物（2 - 4、5a -1 3a和6b、8b - 13b）已基于涉及 5-Bromo-2 缩合的开发系统方法合成,3-二氨基吡啶与合适的芳香醛在水中存在分子碘的情况下，然后使用不同的烷基二溴化剂进行烷基化反应。合成的化合物通过核磁共振光谱技术表征。8a、9a、12a和11b的结构使用单晶 X 射线晶体学确认。在 B3LYP/6-31G++(d,p) 理论水平上使用 DFT 和 TD-DFT 方法进行了理论计算。通过 Hirshfeld 表面分析确定8a、9a、12a和11b单元之间的分子间接触。进行了分子对接研究以确定8a、9a、12a和11b与作为靶酶的金黄色葡萄球菌酪氨酰-tRNA合成酶结合位点的结合亲和力，结果表明9a是所选化合物中最有效的化合物，结合亲和力为 -8.74 Kcal/mol。

由 Ramaswamy H. Sarma 传达