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
Abstract
:1. Introduction
2. Results and Discussion
2.1. Synthesis
2.2. Crystal and Molecular Structure Analysis
2.3. Hirshfeld Surface Analysis
2.4. Quantum Chemistry Calculations of Geometry and Electronic Structure
2.5. Molecular Docking Simulations
2.6. Anti-Hepatitis B Virus (HBV) Activity
3. Materials and Methods
3.1. Chemistry
3.1.1. General Information
3.1.2. Synthesis and Crystallization of Compound (3)
3.2. X-ray Diffraction Study
3.3. Theoretical Calculations
3.4. Docking Studies
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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D—H···A | D—H | H···A | D···A | D—H···A |
---|---|---|---|---|
C1—H1···F1 i | 0.93 | 2.60 | 3.433(5) | 149.0 |
C10—H10···N2 i | 0.93 | 2.53 | 3.417(6) | 159.8 |
C14—H14···O1 ii | 0.93 | 2.56 | 3.346(5) | 143.1 |
C20—H20···C1 | 0.93 | 2.79 | 3.381(6) | 122.5 |
C23—H23···C9 iii | 0.93 | 2.87 | 3.668(6) | 144.3 |
C25-H25A…C21 iiii | 0.93 | 2.74 | 3.572(3) | 144.9 |
Bond/Torsion Angle | Experimental Value (X-ray Study) | Calculated Value, (Vacuum) |
---|---|---|
F1–C9 | 1.358(5) | 1.345 |
F2—C15 | 1.366(5) | 1.342 |
O1—C2 | 1.221(5) | 1.227 |
O2—C24 | 1.362(5) | 1.354 |
O2—C25 | 1.425(5) | 1.411 |
N1—C1 | 1.369(5) | 1.377 |
N1—C2 | 1.400(5) | 1.404 |
N1—C18 | 1.460(4) | 1.472 |
N2—C1 | 1.289(5) | 1.292 |
N2—C4 | 1.375(5) | 1.371 |
N3—C3 | 1.385(5) | 1.377 |
N3—C6 | 1.395(5) | 1.381 |
N3—C11 | 1.449(5) | 1.459 |
C1–N1–C12–C19 | 93.6 | 58.5 |
N1–C18–C19–C20 | −29.1 | −116.1 |
C25–O2–C24–C23 | 8.7 | 1.7 |
C3–N3–C11–C12 | −78.3 | −94.6 |
N3–C11–C12–C17 | −50.7 | −106 |
PDB | Molecule | Affinity (kcal/mol) | Binding Affinity Score |
---|---|---|---|
5E0I | NVR10-001E2 | −21.6 | −28.6 |
molecule (3) | −17.9 | −33.5 | |
5GMZ | 4-methyl heteroaryldihydropyrimidine | −16.18 | −25.95 |
molecule (3) | −16.30 | −31.02 | |
5WRE | HAP-R01 | −21.46 | −38.45 |
molecule (3) | −15.16 | −23.39 | |
5T2P | SBA-R01 | −15.81 | −26.70 |
molecule (3) | −17.14 | −44.42 |
Torsion Angle | Docking Case A | ab Initio Conf. C | Docking Case B | ab Initio Conf. B |
---|---|---|---|---|
N3–C11–C12–C17 | −3.6 | 53.6 | 30.9 | 19 |
N1–C18–C19–C24 | −176.1 | −170 | 63.2 | 60 |
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Ivashchenko, A.V.; Mitkin, O.D.; Kravchenko, D.V.; Kuznetsova, I.V.; Kovalenko, S.M.; Bunyatyan, N.D.; Langer, T. 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. Crystals 2019, 9, 379. https://doi.org/10.3390/cryst9080379
Ivashchenko AV, Mitkin OD, Kravchenko DV, Kuznetsova IV, Kovalenko SM, Bunyatyan ND, Langer T. 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. Crystals. 2019; 9(8):379. https://doi.org/10.3390/cryst9080379
Chicago/Turabian StyleIvashchenko, Aleksandr V., Oleg D. Mitkin, Dmitry V. Kravchenko, Irina V. Kuznetsova, Sergiy M. Kovalenko, Natalya D. Bunyatyan, and Thierry Langer. 2019. "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" Crystals 9, no. 8: 379. https://doi.org/10.3390/cryst9080379