Synthesis, X-ray crystal structure, Hirshfeld surface analysis, and molecular docking study of novel inhibitor of hepatitis B: methyl 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate

Abstract

A method of 4-fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate synthesis has been developed and the electronic and spatial structure of a new biologically active molecule has been studied both theoretically and experimentally. The title compound was crystallized from acetonitrile and the single crystal X-ray analysis has revealed that it exists in a monoclinic P21/c space group, with one molecule in the asymmetric part of the unit cell. Hirshfeld surface analysis was used to study intermolecular interactions in the crystal. Molecular docking study evaluates the investigated compound as a new potential inhibitor of hepatitis B. Testing for anti-hepatitis B virus activity has shown that this substance demonstrates in vitro nanomolar inhibitory activity against HBV.

Crystal structure, Hirshfeld analysis and a molecular docking study of a new inhibitor of the Hepatitis B virus (HBV): ethyl 5-methyl-1,1-dioxo-2-{[5-(pentan-3-yl)-1,2,4-oxadiazol-3-yl]methyl}-2H-1,2,6-thiadiazine-4-carboxylate

“…Heterocyclic homologues of 2H-1,2,6-thiadiazine-1,1-dioxides are inhibitors of human cytomegalovirus (Martínez et al, 2003), Cruzi triposome (Á lvarez et al, 2010) and diuretics (Goya et al, 1992). In a continuation of our efforts to obtain new HBV inhibitors for the treatment and prevention of human HBV infections (Ivachtchenko et al, 2019;Ivashchenko et al, 2019;Kovalenko et al, 2019), we initiated the design, synthesis, and anti-hepatitis B virus activity testing of the new 2H-1,2,6thiadiazine 1,1-dioxide derivative, ethyl 5-methyl-1,1-dioxo-2-{[5-(pentan-3-yl)-1,2,4-oxadiazol-3-yl]methyl}-2H-1,2,6-thiadiazine-4-carboxylate (3).…”

Electronic Characteristics of Thiophenes

“…Линейные зависимости между длинами связей и параметрами электронной плотности в критических точках (КТ) связевых путей при взаимодействии меди с тиофеном, легированном металлами получены в [17]. Изучению КТ связующих линий между тиофеном и другими веществами посвящены материалы [18], а также производных тиофена [19]. Несмотря на широкое использование QTAIM при исследовании тиофена и его соединений, интегральные электронные характеристики атомов и групп (заряд, энергия и объем) ранее рассмотрены не были.…”

Design, Synthesis and Bioactive Evaluation of Oxime Derivatives of Dehydrocholic Acid as Anti-Hepatitis B Virus Agents

“…The disadvantages of nucleoside analogs prompted us and other researchers to invent and find new structural non-nucleoside analog compounds [11][12][13][14][15][16]. Many anti-HBV bioactive non-nucleoside analog compounds have been designed and developed on the basis of their interactions with receptor using molecular docking [17][18][19][20][21]. When HBV receptor binding domain PreS1 and PreS2 protein (including L protein, M protein and S protein) interact with small molecules, the virus will not allow entry to hepatocyte.…”