N-乙酰基-2,4-[二芳基-3-氮杂双环[3.3.1]壬烷-9-基]-9-螺-4'-乙酰基-2'-(乙酰氨基)-4',9-二氢-[1',3',4']-噻二唑的合成、晶体结构、密度泛函理论及分子对接研究：一种潜在的严重急性呼吸综合征冠状病毒2主蛋白酶（COVID-19）抑制剂

Synthesis, crystal structure, DFT and molecular docking studies of N-acetyl-2,4-[diaryl-3-azabicyclo[3.3.1]nonan-9-yl]-9-spiro-4'-acetyl-2'-(acetylamino)-4',9-dihydro-[1',3',4']-thiadiazoles: A potential SARS-nCoV-2 Mpro (COVID-19) inhibitor.

作者信息

Rajamanickam Ramachandran, Mannangatty Rani, Sampathkumar Jayanthi, Senthamaraikannan Kabilan, Diravidamani Barathi

机构信息

Department of Chemistry, PGP College of Arts and Science (Affiliated to Periyar University-Salem), Namakkal, 637 207, Tamil Nadu, India.

Department of Chemistry, Annamalai University, Annamalainagar, 608 002, Tamil Nadu, India.

出版信息

J Mol Struct. 2022 Jul 5;1259:132747. doi: 10.1016/j.molstruc.2022.132747. Epub 2022 Mar 2.

In this paper, we describe the synthesis and crystal structure analysis of N-acetyl-2,4-[diphenyl-3-azabicyclo[3.3.1]nonan-9-yl]-9-spiro-4'-acetyl-2'-(acetylamino)-4',9-dihydro-[1',3',4']-thiadiazole ( and N-acetyl- 2,4-[bis(-methoxyphenyl)-3-azabicyclo[3.3.1]nonan-9-yl]-9-spiro-4'-acetyl-2'-(acetylamino)-4',9-dihydro-[1',3',4']-thiadiazole ). The title compounds and are characterized by 1D NMR and single crystal x-ray diffraction analysis. Non-covalent interactions in a molecule were identified by Hirshfeld surface (d contacts and 2D fingerprint plot) analysis. In addition, the existence of chalcogen bond (S•••O bond) in the molecular structures ( and ) are described by NCI-RDG and QTAIM analysis. NBO analysis is employed to describe the orbital interactions and electron transfer between sulfur and oxygen atoms. Molecular docking is carried out for compounds and with COVID-19 viral protein SARS-nCoV-2 M (PDB ID: 6LU7).

在本文中，我们描述了N-乙酰基-2,4-[二苯基-3-氮杂双环[3.3.1]壬烷-9-基]-9-螺-4'-乙酰基-2'-(乙酰氨基)-4',9-二氢-[1',3',4']-噻二唑（以及N-乙酰基-2,4-[双( -甲氧基苯基)-3-氮杂双环[3.3.1]壬烷-9-基]-9-螺-4'-乙酰基-2'-(乙酰氨基)-4',9-二氢-[1',3',4']-噻二唑）的合成及晶体结构分析。标题化合物通过一维核磁共振和单晶X射线衍射分析进行表征。通过 Hirshfeld 表面（d 接触和二维指纹图谱）分析确定了分子中的非共价相互作用。此外，通过 NCI-RDG 和 QTAIM 分析描述了分子结构（和）中硫属元素键（S•••O 键）的存在。采用自然键轨道（NBO）分析来描述硫和氧原子之间的轨道相互作用和电子转移。对化合物和与 COVID-19 病毒蛋白 SARS-nCoV-2 M（PDB ID：6LU7）进行了分子对接。