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

Alexandre V Ivachtchenko; Oleg D Mitkin; Dmitry V Kravchenko; Sergiy M Kovalenko; Svitlana V Shishkina; Natalya D Bunyatyan; Irina S Konovalova; Irina G Dmitrieva; Vladimir V Ivanov; Thierry Langer

doi:10.1016/j.heliyon.2019.e02738

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

Heliyon. 2019 Nov 14;5(11):e02738. doi: 10.1016/j.heliyon.2019.e02738. eCollection 2019 Nov.

Authors

Affiliations

¹ ChemRar Research and Development Institute, 7 Nobel st., Innovation Center Skolkovo Territory, Moscow, 143026, Russia.
² Chemical Diversity Research Institute, 2A Rabochaya st., Khimki, Moscow Region, 141400, Russia.
³ Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Healthcare of the Russian Federation (Sechenovskiy University), 8 Trubeckaya st., Moscow, 119991, Russia.
⁴ V.N.Karazin Kharkiv National University, 4 Svobody sq., Kharkiv, 61077, Ukraine.
⁵ State Scientific Institution "Institute for Single Crystals" of the National Academy of Sciences of Ukraine, 61001, Kharkov, Ukraine.
⁶ Federal State Budgetary Institution "Scientific Centre for Expert Evaluation of Medicinal Products" of the Ministry of Health of the Russian Federation, Petrovsky Boulevard 8, bld. 2, Moscow, 127051, Russia.
⁷ Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, A-1090, Vienna, Austria.

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.

Keywords: 4-Fluoro-3-(morpholinosulfonyl)benzo[b]thiophene-2-carboxylate; Benzothiophene; HBV; Hepatitis B; Hirshfeld surface analysis; Hydrogen bond; Molecular docking study; Organic chemistry; Pharmaceutical chemistry; Pharmaceutical crystals; Theoretical chemistry.