Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine and Evaluation of Their Antiviral Activity
A series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine and its (<i>S</i>)-enantiomer attached via a 6-aminohexanoyl fragment were synthesized by the reaction of nucleophilic substitution of chlorine in v...
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MDPI AG
2022-06-01
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| Online Access: | https://www.mdpi.com/1420-3049/27/13/4236 |
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| author | Victor P. Krasnov Vera V. Musiyak Galina L. Levit Dmitry A. Gruzdev Valeriya L. Andronova Georgii A. Galegov Iana R. Orshanskaya Ekaterina O. Sinegubova Vladimir V. Zarubaev Valery N. Charushin |
| author_facet | Victor P. Krasnov Vera V. Musiyak Galina L. Levit Dmitry A. Gruzdev Valeriya L. Andronova Georgii A. Galegov Iana R. Orshanskaya Ekaterina O. Sinegubova Vladimir V. Zarubaev Valery N. Charushin |
| author_sort | Victor P. Krasnov |
| collection | DOAJ |
| description | A series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine and its (<i>S</i>)-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 <sup>1</sup>H, <sup>19</sup>F, and <sup>13</sup>C 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. |
| first_indexed | 2024-03-09T04:00:20Z |
| format | Article |
| id | doaj.art-50c2c03af8af4dc3bb1b2360638f7deb |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T04:00:20Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-50c2c03af8af4dc3bb1b2360638f7deb2023-12-03T14:14:00ZengMDPI AGMolecules1420-30492022-06-012713423610.3390/molecules27134236Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine and Evaluation of Their Antiviral ActivityVictor P. Krasnov0Vera V. Musiyak1Galina L. Levit2Dmitry A. Gruzdev3Valeriya L. Andronova4Georgii A. Galegov5Iana R. Orshanskaya6Ekaterina O. Sinegubova7Vladimir V. Zarubaev8Valery N. Charushin9Postovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, RussiaPostovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, RussiaPostovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, RussiaPostovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, RussiaIvanovsky Institute of Virology, Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow 123098, RussiaIvanovsky Institute of Virology, Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Health of the Russian Federation, Moscow 123098, RussiaSaint Petersburg Pasteur Research Institute of Epidemiology and Microbiology, Saint Petersburg 197101, RussiaSaint Petersburg Pasteur Research Institute of Epidemiology and Microbiology, Saint Petersburg 197101, RussiaSaint Petersburg Pasteur Research Institute of Epidemiology and Microbiology, Saint Petersburg 197101, RussiaPostovsky Institute of Organic Synthesis, Russian Academy of Sciences (Ural Branch), Ekaterinburg 620108, RussiaA series of pyrimidine conjugates containing a fragment of racemic 7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine and its (<i>S</i>)-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 <sup>1</sup>H, <sup>19</sup>F, and <sup>13</sup>C 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.https://www.mdpi.com/1420-3049/27/13/4236pyrimidinepurine7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazineantiviral activityHSV-1influenza virus |
| spellingShingle | Victor P. Krasnov Vera V. Musiyak Galina L. Levit Dmitry A. Gruzdev Valeriya L. Andronova Georgii A. Galegov Iana R. Orshanskaya Ekaterina O. Sinegubova Vladimir V. Zarubaev Valery N. Charushin Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine and Evaluation of Their Antiviral Activity Molecules pyrimidine purine 7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine antiviral activity HSV-1 influenza virus |
| title | Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine and Evaluation of Their Antiviral Activity |
| title_full | Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine and Evaluation of Their Antiviral Activity |
| title_fullStr | Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine and Evaluation of Their Antiviral Activity |
| title_full_unstemmed | Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine and Evaluation of Their Antiviral Activity |
| title_short | Synthesis of Pyrimidine Conjugates with 4-(6-Amino-hexanoyl)-7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine and Evaluation of Their Antiviral Activity |
| title_sort | synthesis of pyrimidine conjugates with 4 6 amino hexanoyl 7 8 difluoro 3 4 dihydro 3 methyl 2 i h i 1 4 benzoxazine and evaluation of their antiviral activity |
| topic | pyrimidine purine 7,8-difluoro-3,4-dihydro-3-methyl-2<i>H</i>-[1,4]benzoxazine antiviral activity HSV-1 influenza virus |
| url | https://www.mdpi.com/1420-3049/27/13/4236 |
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