Abstract

In this work we report detailed structural and computational studies of 6-amino-2-(4-fluorophenyl)-4-(trifluoromethyl)quinoline (1). The structure is stabilized by the intramolecular N–H···N hydrogen bonds, C–H···F interactions, π···π interactions and C–F···F–C interactions. The listed interactions are also reflected on the Hirshfeld surfaces as well as the corresponding 2D fingerprint plots, which revealed that the crystal packing of 1 is mainly dictated by highly favored H···H and H···F contacts followed by also favored H···N, C···C and F···F contacts. The DFT calculations were performed to verify the structure of 1 as well as its electronic and optical properties. Compound 1 was predicted to exhibit preferred results for drug candidates in five parameters, namely lipophilicity, size, polarity, insolubility and flexibility. Furthermore, it was predicted that 1 is likely a potential inhibitor of family A G protein-coupled receptor and kinase; electrochemical transporter and voltage-gated ion channel; oxidoreductase, hydrolase, protease, family C G protein-coupled receptor and primary active transporter with the probabilities of 20.0%, 13.3% and 6.7%, respectively. At the same time, 1 was found to be active against Aryl hydrocarbon Receptor (AhR) and Mitochondrial Membrane Potential (MMP), hepatotoxic and mutagenic. According to the BOILED-Egg method for 1 the human blood-brain barrier (BBB) penetration property is negative and gastrointestinal absorption property is positive with the positive PGP effect on the molecule.

摘要

在这项工作中，我们报告了 6-amino-2-(4-fluorophenyl)-4-(trifluoromethyl)quinoline ( 1 ) 的详细结构和计算研究。该结构通过分子内N–H···N氢键、C–H···F相互作用、π···π相互作用和C–F···F–C相互作用稳定。列出的相互作用也反映在 Hirshfeld 表面以及相应的二维指纹图上，这表明1的晶体堆积主要由高度有利的 H···H 和 H···F 接触决定，其次是也有利的 H ···N、C···C、F···F接点。进行 DFT 计算以验证1的结构及其电子和光学特性。化合物1预计在五个参数中显示候选药物的优选结果，即亲脂性、大小、极性、不溶性和柔韧性。此外，预测1可能是 AG 家族蛋白偶联受体和激酶的潜在抑制剂；电化学转运蛋白和电压门控离子通道；氧化还原酶、水解酶、蛋白酶、CG 家族蛋白偶联受体和初级活性转运蛋白的概率分别为 20.0%、13.3% 和 6.7%。同时，发现1对芳烃受体 (AhR) 和线粒体膜电位 (MMP) 具有活性，具有肝毒性和致突变性。根据1的 BOILED-Egg 方法人血脑屏障（BBB）穿透性为负，胃肠道吸收性为正，分子具有正PGP作用。