This study investigates the crystal structure, physicochemical properties, and pharmacokinetic profile of Ethyl 2-amino-6-methyl-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3-carboxylate (EAMT) as a potential therapeutic agent. The crystal structure was analyzed using Hirshfeld surface analysis in conjunction with the quantum theory of atoms in molecules (QT-AIM). Non-covalent interactions were evaluated through reduced-density gradient reduction, revealing that the EAMT crystal is stabilized by hydrogen bonds between EAMT molecules in the crystal and between EAMT molecules and water molecules. The molecular electrostatic nature of interactions was examined using MESP, while global and local descriptors were calculated to assess the compound’s reactivity. Molecular docking with the Adenosine A1 receptor was performed and validated through a 50 ns molecular dynamics simulation (MDS). Results suggest that EAMT influences protein structure, potentially stabilizing specific secondary structure elements. The compactness analysis showed a slightly more compact protein conformation and a marginally increased solvent exposure in the presence of the EAMT ligand, as indicated by Rg and SASA values. The total binding free energy (ΔG total) was determined to be −114.56 kcal/mol. ADMET predictions demonstrated EAMT’s compliance with Lipinski’s and Pfizer’s rule of five, indicating good oral availability. The compound may exhibit low-potency endocrine activity. In conclusion, EAMT presents potential as a therapeutic candidate, warranting further exploration of its molecular interactions, pharmacokinetics, and potential safety concerns.

中文翻译：

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利用计算方法探索四氢噻吩并吡啶衍生物的化学反应性、分子对接、分子动力学模拟和 ADMET 性质

本研究调查了 2-氨基-6-甲基-4,5,6,7-四氢噻吩并[2,3-c]吡啶-3-甲酸乙酯 (EAMT) 作为潜在药物的晶体结构、理化性质和药代动力学特征治疗剂。使用赫什菲尔德表面分析结合分子中原子量子理论 (QT-AIM) 来分析晶体结构。通过降低密度梯度还原评估非共价相互作用，揭示了 EAMT 晶体通过晶体中 EAMT 分子之间以及 EAMT 分子与水分子之间的氢键稳定。使用 MESP 检查相互作用的分子静电性质，同时计算全局和局部描述符以评估化合物的反应性。通过 50 ns 分子动力学模拟 (MDS) 进行并验证了与腺苷 A1 受体的分子对接。结果表明 EAMT 影响蛋白质结构，可能稳定特定的二级结构元件。紧密度分析显示，在 EAMT 配体存在的情况下，蛋白质构象稍微更紧凑，溶剂暴露略有增加，如 Rg 和 SASA 值所示。总结合自由能（ΔG 总）测定为-114.56 kcal/mol。ADMET 预测表明 EAMT 符合 Lipinski 和辉瑞的五法则，表明口服可用性良好。该化合物可能表现出低效的内分泌活性。总之，EAMT 具有作为候选治疗药物的潜力，值得进一步探索其分子相互作用、药代动力学、