S 98 Synthesis and antiviral activity of nucleoside analogs based on 1,2,4-triazolo[3,2-c][1,2,4]triazin-7-ones [Electronic resource] / V. L. Rusinov, O. N. Chupakhin, S. L. Deev, T. S. Shestakova, E. N. Ulomskii, L. I. Rusinova, O. I. Kiselev, E. G. Deeva // Russian Chemical Bulletin (Translation of Izvestiya Akademii Nauk, Seriya Khimicheskaya). - 2010. - Vol. 59, № 1. - P136-143 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): NUCLEOSIDE ANALOGS -- ANTIVIRAL DRUGS -- HYDROXYETHOXYMETHYL Аннотация: Nucleoside analogs containing hydroxybutyl, hydroxyethoxymethyl, allyloxymethyl, and propargyloxymethyl fragments were synthesized based on 1,2,4-triazolo[3,2-c][1,2,4]triazin-7-ones isosteric to purine bases. Some of the compounds obtained inhibit in vitro reproduction of influenza and respiratory syncytial virus infection \\\\Expert2\\nbo\\Russian Chemical Bulletin\\2010, 59 (1), 136-143.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. - 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 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 |
6-Aminotriazolo[1,5-a]pyrimidines as precursors of 1,2,4-triazolo[5,1-b]purines [Electronic resource] / K. V. Savateev, S. S. Borisov, E. K. Voinkov, E. N. Ulomskii, V. L. Rusinov, O. N. Chupakhin // Chimica Techno Acta. - 2015. - Vol. 2, № 2. - С. 127-128. - Bibliogr. : p. 128 (2 ref.) Аннотация: Triazolo[5,1-b]purines are rare structural analogues of natural nucleosides and nucleobases purine series. At the same time, prominent representatives of azolopurines exhibit a broad spectrum of antiviral effect, activity against of rheumatoid arthritis, psoriasis, Alzheimer’s, Parkinson’s and etc. Despite the practical value azolo[5,1-b]purines extremely sparingly represented in the chemical literature, due to the complexity of their synthesis. We suggest a convenient way to synthesize triazolopurines with aminotriazolo[1,5-a]pyrimidines (2) as available starting compounds obtained in good yield by reduction of nitro derivatives (1). \\\\expert2\\nbo\\Chimica Techno Acta\\2015. V. 2, N 2. P. 127-128.pdf |
S 98 Synthesis of novel purin-6-yl conjugates with heterocyclic amines linked via 6-aminohexanoyl fragment [Electronic resource] / E. V. Verbitskiy, E. M. Cheprakova, P. A. Slepukhin, M. A. Kravchenko, S. N. Skornyakov, G. L. Rusinov, O. N. Chupakhin, V. N. Charushin // Mendeleev Communications. - 2015. - Vol. 25. - С. 412-414. - Bibliogr. : p. 414 (30 ref.) Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): 2-AMINOPURINE -- PURIN-6-YL -- HETEROCYCLIC AMINES Аннотация: Novel conjugates of purine and 2-aminopurine linked with heterocyclic amines, including chiral derivatives of 3,4-dihydro- 2H-[1,4]benzoxazine, 3,4-dihydro-2H-[1,4]benzothiazine and 1,2,3,4-tetrahydroquinoline, by 6-aminohexanoyl fragment at the 6-position of purine moiety were obtained. For this purpose, replacement of the chlorine atom in 2-amino-6-chloropurine or 6-chloropurine by direct nucleophilic substitution reaction with 6-aminohexanamides or the coupling of 6-(purin-6-ylamino)-6- hexanoic acid with nitrogen heterocycles were used. \\\\expert2\\nbo\\Mendeleev Communications\\2015, v.25, p. 412.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 51 Chemoenzymic arabinosylation of 2-aminopurine bearing the chiral fragment of 7,8-difluoro-3-methyl-3,4-dihydro-2H-[1,4]benzoxazines [Electronic resource] / B. Z. Eletskaya, I. D. Konstantinova, A. S. Paramonov, S. E. Esipov, D. A. Gruzdev, A. Yu. Vigorov, G. L. Levit, A. I. Miroshnikov, V. P. Krasnov, V. N. Charushin // Mendeleev Communications. - 2016. - Vol. 26, № 1. - С. 6-8 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): PURINE NUCLEOSIDE PHOSPHORYLASE -- 2-AMINOPURINE CONJUGATES Аннотация: Chemoenzymic transglycosylation of 2-aminopurine conjugates with enantiomerically pure 7,8-difluoro-3-methyl-3,4-dihydro-2H-[1,4]benzoxazines under the action of recombinant E. coli purine nucleoside phosphorylase afforded the corresponding arabinofuranosides, yields of the target compds. being dependent on both the structure and configuration of the fragment of heterocyclic amine attached at C-6 position of purine moiety. \\\\expert2\\nbo\\Mendeleev Communications\\2016, v.26, p. 6-8.pdf |
S 98 Synthesis and antimycobacterial activity of N-(2-aminopurin-6-yl) and N-(purin-6-yl) amino acids and dipeptides [Electronic resource] / V. P. Krasnov, A. Yu. Vigorov, V. V. Musiyak, I. A. Nizova, D. A. Gruzdev, T. V. Matveeva, G. L. Levit, V. N. Charushin // Bioorganic and Medicinal Chemistry Letters. - 2016. - Vol. 26, № 11. - С. 2645-2648 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): PURINE -- GLUTAMIC ACID -- AMINO ACIDS Аннотация: Synthetic routes to novel N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates with amino acids and glycine-containing dipeptides were developed. In vitro testing of 42 new and known compounds made it possible to reveal a series of N-(purin-6-yl)- and N-(2-aminopurin-6-yl) conjugates exhibiting significant antimycobacterial activity against Mycobacterium tuberculosis H37Rv, Mycobacterium avium, Mycobacterium terrae, and multidrug-resistant M. tuberculosis strain isolated from tuberculosis patients in the Ural region (Russia). N-(2-Aminopurin-6-yl)- and N-(purin-6-yl)-glycyl-(S)-glutamic acids were the most active compounds. (C) 2016 Elsevier Ltd. All rights reserved \\\\expert2\\NBO\\Bioorganic and Medicinal Chemistry Letters\\2016, v. 26, p. 2645.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 89 Novel purine conjugates with N-heterocycles: synthesis and anti-influenza activity / V. P. Krasnov, V. V. Zarubaev, D. V. Gruzdev [et al.] // Chemistry of Heterocyclic Compounds. - 2021. - Vol. 57, № 4. - P498-504
Кл.слова (ненормированные): 6-CHLOROPURINE -- HETEROCYCLIC AMINES -- ANTIVIRAL ACTIVITY -- INFLUENZA A AND B VIRUSES Аннотация: A number of novel amides were synthesized by coupling of 6-[(9H-purin-6-yl)amino]hexanoic acid to heterocyclic amines. The antiviral activity of the obtained compounds, as well as of purine conjugates in which 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine is linked to position 6 of purine through a fragment of ɷ-amino acids with varying lengths of polymethylene chains against influenza A and B viruses was studied in vitro. Purine derivatives have been shown to have moderate activity against influenza A (H1N1) virus. The antiinfluenza activity and cytotoxicity of conjugates with 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine depend on the length of the linker fragment. |
S 98 Synthesis and antiherpetic activity of novel purine conjugates with 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine / O. A. Vozdvizhenskaya, V. L. Andronova, G. A. Galegov [et al.] // Chemistry of Heterocyclic Compounds. - 2021. - Vol. 57, № 4. - P490–497 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): 6-CHLOROPURINE -- ANTIVIRAL ACTIVITY -- HERPES SIMPLEX VIRUS TYPE 1 Аннотация: A method for the synthesis of novel purine conjugates with 7,8-difluoro-3-methyl-3,4-dihydro-2H-1,4-benzoxazine containing fragments of ω-amino acids with different lengths of the polymethylene chain as a linker has been developed. It was found in experiments in vitro that the obtained compounds are active against the herpes simplex virus type 1, including the acyclovir-resistant strain. |
S 83 Stereochemical aspects in the synthesis of novel N-(purin-6-yl)dipeptides as potential antimycobacterial agents / V. V. Musiyak, I. A. Nizova, E. N. Chulakov [et al.] // Amino Acids. - 2021. - Vol. 53, № 3. - P407-415 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): DIPEPTIDES -- RACEMIZATION -- PURINE -- COUPLING -- NUCLEOPHILIC SUBSTITUTION -- ANTIMYCOBACTERIAL ACTIVITY Аннотация: The synthesis of purine conjugates with natural amino acids is one of the promising directions in search for novel therapeutic agents, including antimycobacterial agents. The purpose of this study was to synthesize N-(purin-6-yl)dipeptides containing the terminal fragment of (S)-glutamic acid. To obtain the target compounds, two synthetic routes were tested. The first of them is based on coupling of N-(purin-6-yl)-(S)-amino acids to dimethyl (S)-glutamate in the presence of carbodiimide coupling agent followed by the removal of ester groups. However, it turned out that this coupling process was accompanied by racemization of the chiral center of N-(purin-6-yl)-α-amino acids and in all cases led to mixtures of (S,S)- and (R,S)diastereomers (6:4). Individual (S,S)-diastereomers were obtained using an alternative approach based on the nucleophilic substitution of chlorine in 6-chloropurine or 2-amino-6-chloropurine with corresponding dipeptides as nucleophiles. The enantiomeric purity of the target compounds was confirmed by chiral HPLC. To test the assumption that racemization of the chiral center of N-(purin-6-yl)-α-amino acids occurs with the participation of nitrogen atoms of the imidazole ring via the stage of formation of a chirally labile intermediate, we obtained such structural analogs of N-(purin-6-yl)-(S)-alanine as N-(9-benzylpurin-6-yl)-(S)-alanine and N-(7-deazapurin-6-yl)-(S)-alanine. It was found that coupling of these compounds to dimethyl (S)-glutamate was also accompanied by racemization. This indicates that the imidazole fragment does not play a crucial role in this process. When testing the antimycobacterial activity of some of the obtained compounds, conjugates with moderate activity against the laboratory Mycobacterium tuberculosis H37Rv strain (MIC 3.1–6.25 μg/mL) were identified. |
New nido-carborane-containing conjugates of purine: synthesis and antiviral activity / D. A. Gruzdev, A. A. Telegina, V. A. Ol’shevskaya [et al.] // Russian chemical bulletin. - 2022. - Vol. 71, № 11. - P2375-2382 Рубрики: ЗДРАВООХРАНЕНИЕ. МЕДИЦИНСКИЕ НАУКИ ХИМИЧЕСКИЕ НАУКИ Аннотация: New purine derivatives containing a nido-carborane fragment were synthesized by nucleophilic substitution of chlorine atom in 6-chloropurine and 2-amino-6-chloropurine under the action of nido-carborane-containing amines. Compounds with significant activity against the acyclovir-resistant strain of herpes simplex virus type 1, as well as with moderate activity against influenza viruses A and B, were discovered for the first time among the synthesized nido-carboranyl derivatives of purine. |
Synthesis of new conjugates of 6-thiopurine and thioguanine with (S)-glutamic acid / A. A. Telegina, D. A. Gruzdev, G. L. Levit, V. P. Krasnov // Russian chemical bulletin. - 2022. - Vol. 71, № 11. - P2426-2430 Рубрики: ХИМИЧЕСКИЕ НАУКИ Аннотация: We have developed an efficient method for the synthesis of 6-thiopurine and thioguanine conjugates containing a (S)-glutamic acid residue, which is based on the reaction of 6-thio derivatives of purine with di-tert-butyl N-chloroacetyl-(S)-glutamate and subsequent hydrolysis of the ester groups. |
Synthesis of pyrimidine conjugates with 4-(6-amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2h-[1,4] benzoxazine and evaluation of their antiviral activity / V. P. Krasnov, V. V. Musiyak, G. L. Levit [et al.] // Molecules. - 2022. - Vol. 27, № 13. - Ст. 4236 Рубрики: ХИМИЧЕСКИЕ НАУКИ Кл.слова (ненормированные): PYRIMIDINE Аннотация: A series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]benzoxazine and its (S)-enantiomer attached via a 6-aminohexanoyl fragment were synthesized by the reaction of nucleophilic substitution of chlorine in various chloropyrimidines. The structures of the synthesized compounds were confirmed by 1H, 19F, and 13C NMR spectral data. Enantiomeric purity of optically active derivatives was confirmed by chiral HPLC. Antiviral evaluation of the synthesized compounds has shown that the replacement of purine with a pyrimidine fragment leads to a decrease in the anti-herpesvirus activity compared to the lead compound, purine conjugate. The studied compounds did not exhibit significant activity against influenza A (H1N1) virus. |