A 99 Azolo[5,1-c]-1,2,4-triazines as a new class of antiviral compounds [Electronic resource] / V. L. Rusinov, E. N. Ulomskii, V. N. Charushin, O. N. Chupakhin // Russian Chemical Bulletin (Translation of Izvestiya Akademii Nauk, Seriya Khimicheskaya). - 2008. - Vol. 57, № 5. - P985-1014 Рубрики: ХИМИЧЕСКИЕ НАУКИ Аннотация: Synthetic methods, reactivity, and the properties of a new class of antiviral compounds, pyrazolo-, imidazo-, 1,2,4-triazolo[5,1-c]-1,2,4-triazinones, tetrazolo[5,1-b]-1,2,4-triazinones, and azoloannulated amino-1,2,4-triazines having structural similarity with biogenic purines and capable of mimicking them in metabolic processes are considered \\\\Expert2\\nbo\\Russian Chemical Bulletin\\2008, 57 (5), 985.pdf |
Chemo-Enzymatic Synthesis and Biological Evaluation of 5,6-Disubstituted Benzimidazole Ribo- and 2′-Deoxyribonucleosides / I. D. Konstantinova, O. M. Selezneva, S. K. Kotovskaya, Z. M. Baskakova, V. N. Charushin, A. V. Baranovsky // Synthesis. - 2012. - Vol.45. - Article in press Кл.слова (ненормированные): 5,6-DISUBSTITUTED BENZIMIDAZOLES -- NUCLEOSIDES -- PURINE NUCLEOSIDE PHOSPHORYLASE Аннотация: A number of new 5,6-disubstituted benzimidazoles have been prepared and their substrate properties for recombinant E. coli purine nucleoside phosphorylase (PNP; the product of the deoD gene) in the transglycosylation reaction were investigated. The heterocyclic- bases showed good substrate activity for PNP and the ribo- and 2′-deoxyribonucleosides were synthesized. The predominant (OMe and OEt) or exclusive (Oi-Pr, morpholino, and N-methylpiperazino) formation of the 5-substituted 6-fluoro-1-(β-D-ribofuranosyl)benzimidazoles was observed. The formation of the regioisomeric 6- methoxy-, 6-ethoxy-, or 6-isopropoxy-substituted 1-(2-deoxy-β-D-ribofuranosyl)-5-fluorobenzimidazoles was observed in the trans-2-deoxyribosylation reaction of the corresponding bases. The predominant or exclusive formation of the regioisomeric N1-nucleosides with bulky 5-substituents of 6-fluorobenzimidazole points to a large hydrophobic pocket in the E. coli PNP active site that can accommodate these groups. The biological activity of the synthesized nucleosides was studied and revealed no inhibitory activity against a broad variety of DNA and RNA viruses. The compounds also lacked significant cy \\\\expert2\\nbo\\Synthesis\\2012, Article in press.pdf |
C 51 Chemo-enzymatic synthesis and biological evaluation of 5,6-disubstituted benzimidazole ribo- and 2′-deoxyribonucleosides [Электронный ресурс] / I. D. Konstantinova, O. M. Selezneva, I. V. Fateev, T. A. Balashova, S. K. Kotovskaya, Z. M. Baskakova, V. N. Charushin, I. A. Mikhailopulo // Synthesis (Germany). - 2013. - Vol.45, №2, art. N SS-2012-T0784-OP. - P272-280 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): 5,6-DISUBSTITUTED BENZIMIDAZOLES -- NUCLEOSIDES -- SUBSTRATE PROPERTIES Аннотация: A number of new 5,6-disubstituted benzimidazoles have been prepared and their substrate properties for recombinant E. coli purine nucleoside phosphorylase (PNP; the product of the deoD gene) in the transglycosylation reaction were investigated. The heterocyclic bases showed good substrate activity for PNP and the ribo- and 2-deoxyribonucleosides were synthesized. The predominant (OMe and OEt) or exclusive (Oi-Pr, morpholino, and N-methylpiperazino) formation of the 5-substituted 6-fluoro-1-(β-d- ribofuranosyl)benzimidazoles was observed. The formation of the regioisomeric 6- methoxy-, 6-ethoxy-, or 6-isopropoxy-substituted 1-(2-deoxy-β-d- ribofuranosyl)-5-fluorobenzimidazoles was observed in the trans-2- deoxyribosylation reaction of the corresponding bases. The predominant or exclusive formation of the regioisomeric N1-nucleosides with bulky 5-substituents of 6-fluorobenzimidazole points to a large hydrophobic pocket in the E. coli PNP active site that can accommodate these groups. The biological activity of the synthesized nucleosides was studied and revealed no inhibitory activity against a broad variety of DNA and RNA viruses. The compounds also lacked significant cytotoxicity \\\\expert2\\nbo\\Synthesis\\2013, v. 45. N 2. p. 272-280.pdf |
R 30 Reactions of N-alkylazinium cations. 3. Quaternary pteridinium salts. Synthesis, structure, and reactions with simple nucleophiles [Electronic resource] / I. V. Kazantseva, V. N. Charushin, O. N. Chupakhin, A. I. Chernyshev, S. E. Esipov // Chemistry of Heterocyclic Compounds. - 1985. - Vol. 21, № 9. - С. 1048-1055. - Bibliogr. : p. 1054-1055 (14 ref.) Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): 4-Morpholinopteridine -- TRIETHYLOXONIUM TETRA-FLUOROBORATE -- NUCLEOSIDES Аннотация: 4-Morpholinopteridine reacts with triethyloxonium tetra-fluoroborate to give two types of isomeric quaternary salts, viz., 1-ethyl- and 8-ethyl-4-morpholinopteridinium tetrafluoroborates. The structures of the pteridinium cations were proved by the 1H and 13C NMR spectra and also by chemical transformations in reactions with simple nucleophiles. \\\\expert2\\nbo\\Chemistry of Heterocyclic Compounds\\1985, v.21, N 9, p. 1048.pdf |
B 60 Biotechnological synthesis of new nucleosides based on 2-aminopurine with a bulky 7,8-difluoro-3,4-dihydro-3-methyl-2 h-[1,4]benzoxazine residue at C6 position [Electronic resource] / B. Z. Eletskaya, D. A. Gruzdev, A. Yu. Vigorov, I. D. Konstantinova, G. L. Levit, V. P. Krasnov, V. N. Charushin, A. I. Miroshnikov // FEBS Journal. - 2015. - Vol. 282, № S1 : 40th Congress of the Federation-of-European-Biochemical-Societies (FEBS) - The Biochemical Basis of Life, Berlin, Germany, Jul 04-09 2015. - С. 162 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): BIOTECHNOLOGICAL SYNTHESIS -- 2-AMINOPURINE -- NUCLEOSIDES |
Chemo-Enzymatic Synthesis and Biological Evaluation of 5,6-Disubstituted Benzimidazole Ribo- and 2′-Deoxyribonucleosides / I. D. Konstantinova, O. M. Selezneva, S. K. Kotovskaya, Z. M. Baskakova, V. N. Charushin, A. V. Baranovsky // Synthesis. - 2013. - Vol.45, № 2. - С. 272-280 Кл.слова (ненормированные): 5,6-DISUBSTITUTED BENZIMIDAZOLES -- NUCLEOSIDES -- PURINE NUCLEOSIDE PHOSPHORYLASE Аннотация: A number of new 5,6-disubstituted benzimidazoles have been prepared and their substrate properties for recombinant E. coli purine nucleoside phosphorylase (PNP; the product of the deoD gene) in the transglycosylation reaction were investigated. The heterocyclic- bases showed good substrate activity for PNP and the ribo- and 2′-deoxyribonucleosides were synthesized. The predominant (OMe and OEt) or exclusive (Oi-Pr, morpholino, and N-methylpiperazino) formation of the 5-substituted 6-fluoro-1-(β-D-ribofuranosyl)benzimidazoles was observed. The formation of the regioisomeric 6- methoxy-, 6-ethoxy-, or 6-isopropoxy-substituted 1-(2-deoxy-β-D-ribofuranosyl)-5-fluorobenzimidazoles was observed in the trans-2-deoxyribosylation reaction of the corresponding bases. The predominant or exclusive formation of the regioisomeric N1-nucleosides with bulky 5-substituents of 6-fluorobenzimidazole points to a large hydrophobic pocket in the E. coli PNP active site that can accommodate these groups. The biological activity of the synthesized nucleosides was studied and revealed no inhibitory activity against a broad variety of DNA and RNA viruses. The compounds also lacked significant cy \\\\expert2\\nbo\\Synthesis\\2013, v. 45. N 2. p. 272-280.pdf |
C 51 Chemoenzymatic Synthesis and Antiherpes Activity of 5-Substituted 4,6-Difluorobenzimidazoles Ribo- and 2′-Deoxyribonucleosides [Электронный ресурс] / M. I. Kharitonova, I. V. Fateev, A. L. Kayushin, I. D. Konstantinova, S. K. Kotovskaya, V. L. Andropova, G. A. Galegov, V. N. Charushin, A. I. Miroshnikov // Synthesis (Germany). - 2016. - Vol. 48, № 3. - С. 394-406. - Bibliogr. : p. 405-406 (37 ref.) Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): DRUG DISCOVERY- -- NUCLEOSIDES -- HERPES SIMPLEX VIRUS Аннотация: A series of 5,6-disubstituted benzimidazole nucleosides, obtained earlier, did not show any significant antiviral activity at relatively low cytotoxicity in vitro. In the course of our research we have succeeded in introducing an additional fluorine atom into the benzimidazole ring system. A new series of 4,6-difluorobenzimidazoles, bearing various groups (fluoro-, methoxy-, ethoxy-, morpholino-, and pyrrolidino-) in the 5-position of the benzene ring, have been synthesized. All these compounds proved to be substrates for recombinant E. coli purine nucleoside phosphorylase (PNP) in the transglycosylation reaction. Effective methods for the synthesis of ribo- and 2′-deoxyribonucleosides with high yields (60–90%) have been described, and the formation of regioisomeric N3-nucleosides of benzimidazoles have been detected. The biological activity of the nucleosides obtained against herpes simplex virus type 1 (HSV-1) has been elucidated. All compounds show a low cytotoxicity in the cell culture Vero E6. 4,5,6-Trifluoro-1-(β-d-ribofuranosyl)benzimidazole and 5-methoxy-4,6-difluoro-1-(β-d-2′-deoxyribofuranosyl)benzimidazole proved to inhibit completely the progression of the virus cytopathic effect (CPE) at a multiplicity of infection (MOI) of 0.01 PFU/cell. \\\\expert2\\nbo\\Synthesis\\2016, v. 48. p.394-406.pdf |
C 57 Chupakhin, O. N. Scientific foundations for the creation of antiviral and antibacterial preparations [Electronic resource] / O. N. Chupakhin, V. N. Charushin, V. L. Rusinov // Herald of the Russian Academy of Sciences. - 2016. - Vol. 86, № 3. - С. 206-212 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): TRIAZIDE AND AZOLOAZINE DERIVATIVES -- TRIAZAVIRIN -- PROTEIN DISULFIDE ISOMERASE Аннотация: The results of the Ural scientific school's organic chemists on the creation of antiviral and antibacterial, including antitubercular, chemopreparations are considered. Basic research data were generalized on the synthesis and study of antiviral activity and the establishment of the metabolism and mechanism of azoloazine series compounds-azaanalogs of adenine and guanine, as well as their nucleosides, which led to the creation of a new family of antiviral substances. One of them, triazavirin, has become a regular therapeutic fixture as an antiflu preparation. The results of synthetic and biological studies on substituted pyrimidines, nucleosides of the benzimidazole and purine series, and other biologically active azaheterocycles are also discussed. \\\\expert2\\NBO\\Herald of the Russian Academy of Sciences\\2016. V. 86, N 3. P. 206-212.pdf |
C 51 Chemoenzymatic Synthesis of Modified 2′-Deoxy-2′-fluoro-β-d-arabinofuranosyl Benzimidazoles and Evaluation of Their Activity Against Herpes Simplex Virus Type 1 / M. I. Kharitonova, K. V. Antonov, I. V. Fateev, M. Ya. Berzina, S. K. Kotovskaya, V. N. Charushin // Synthesis (Germany). - 2017. - Vol. 49, № 5. - С. 1043-1052 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): CHEMOENZYMATIC SYNTHESIS -- BENZIMIDAZOLES -- HERPES SIMPLEX VIRUS TYPE 1 Аннотация: 1-(2′-Deoxy-2′-fluoro-β-d-arabinofuranosyl)benzimidazoles containing 4,6-difluoro-, 4,5,6-trifluoro-, 5-fluoro-6-methoxy-, and 5-methoxy-4,6-difluorobenzimidazole fragments were synthesized by using purine nucleoside phosphorylase-catalyzed chemoenzymatic approach. As expected, enzymatic synthesis of nucleosides proceeds in lower yields of target compounds in comparison with the synthesis of ribo- and 2′-deoxyribobenzimidazoles (40–55% vs 60–90%). The compounds obtained were tested against the herpes simplex virus type 1, by using the Vero E6 cells. 5-Methoxy-4,6-difluoro-1-β-d-(2′-deoxy-2′-fluoroarabinofuranosyl)benzimidazole did not show any antiviral activity, when used in nontoxic concentration. All other nucleosides proved to exhibit a selective antiherpes activity. In contrast, it was shown that benzimidazole-β-d-arabinofuranosides of both di- and trisubstituted derivatives, having substituents in positions 4–6 of the benzene ring, as well as unsubstituted compounds, cannot be synthesized by enzymatic transglycosylation. 1-(β-d-Arabinofuranosyl)benzimidazole was obtained through glycosylation of N-trimethylsilylbenzimidazole with 1-chloro-2,3,5-O-methoxymethyl-d-arabinose. The behavior of this compound, as inhibitor of purine nucleoside phosphorylase (PNP) E. сoli, was investigated. 1-(β-d-Arabinofuranosyl)benzimidazole was found to belong to a mixed type of inhibitors of PNP. This fact explains why all attempts to perform enzymatic arabinosylation of 4,6-di-, 5,6-di-, and 4,5,6-trisubstituted benzimidazoles failed \\\\expert2\\NBO\\Synthesis\\2017, v. 49(5), p. 1043-1052.pdf |
N 52 New modified 2-aminobenzimidazole nucleosides: Synthesis and evaluation of their activity against herpes simplex virus type 1 / M. I. Kharitonova, A. O. Denisova, A. L. Kayushin, I. D. Konstantinova, A. I. Miroshnikov, S. K. Kotovskaya, V. N. Charushin, V. L. Andronova, G. A. Galegov // Bioorganic and Medicinal Chemistry Letters. - 2017. - Vol. 27, № 11. - P2484-2487 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): ANTIVIRAL ACTIVITY -- BENZIMIDAZOLES -- FLUORINATED COMPOUNDS -- NUCLEOSIDE PHOSPHORYLASES -- NUCLEOSIDES -- TRANSGLYCOSYLATION REACTION Аннотация: Using the enzymatic transglycosylation reaction β-d-ribo- and 2′-deoxyribofuranosides of 2-amino-5,6-difluorobenzimidazole nucleosides have been synthesized. 2-Amino-5,6-difluoro-benzimidazole riboside proved to exhibit a selective antiviral activity (selectivity index >32) against a wild strain of the herpes simplex virus type 1, as well as towards virus strains that are resistant to acyclovir, cidofovir, and foscarnet. We believe that this compound might be used for treatment of herpes infections in those cases, when acyclovir is not efficient. \\\\Expert2\\NBO\\Bioorganic and Medicinal Chemistry Letters\\2017 v.27 p.2484-2487.pdf |