Synthesis, X-Ray Crystal Structure, Hirshfeld Surface Analysis, and Molecular Docking Study of Novel Hepatitis B (HBV) Inhibitor: 8-Fluoro-5-(4-fluorobenzyl)-3-(2-methoxybenzyl)-3,5-dihydro-4H-pyrimido[5,4-b]indol-4-one
Aleksandr V. Ivashchenko,
Oleg D. Mitkin,
Dmitry V. Kravchenko,
Irina V. Kuznetsova,
Sergiy M. Kovalenko,
Natalya D. Bunyatyan,
Thierry Langer
Affiliations
Aleksandr V. Ivashchenko
ChemRar Research and Development Institute, 7 Nobel st., Innovation Center Skolkovo Territory, 143026 Moscow, Russia
Oleg D. Mitkin
ChemRar Research and Development Institute, 7 Nobel st., Innovation Center Skolkovo Territory, 143026 Moscow, Russia
Dmitry V. Kravchenko
Chemical Diversity Research Institute, 2A Rabochaya st., Khimki, 141400 Moscow Region, Russia
Irina V. Kuznetsova
Chemical Diversity Research Institute, 2A Rabochaya st., Khimki, 141400 Moscow Region, Russia
Sergiy M. Kovalenko
ChemRar Research and Development Institute, 7 Nobel st., Innovation Center Skolkovo Territory, 143026 Moscow, Russia
Natalya D. Bunyatyan
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., 119991 Moscow, Russia
Thierry Langer
Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria
A method for the synthesis of 8-fluoro-5-(4-fluorobenzyl)-3-(2-methoxybenzyl)-3,5-dihydro-4H-pyrimido[5,4-b]indol-4-one 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/n space group, with one molecule in the asymmetric part of the unit cell, a = 16.366(3) Å, b = 6.0295(14) Å, c = 21.358(4) Å, β = 105.21(2)°, V = 2033.7(7) Å3 and Z = 4. Hirshfeld surface analysis was used to study intermolecular interactions in the crystal. Molecular docking studies have evaluated the investigated compound as a new inhibitor of hepatitis B. Testing for anti-hepatitis B virus activity has shown that this substance has in vitro nanomolar inhibitory activity against Hepatitis B virus (HBV).
