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C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation
The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine in...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270122/ https://www.ncbi.nlm.nih.gov/pubmed/23644977 http://dx.doi.org/10.3390/molecules18055104 |
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author | Meščić, Andrijana Krištafor, Svjetlana Novaković, Ivana Osmanović, Amar Müller, Ursina Završnik, Davorka Ametamey, Simon M. Scapozza, Leonardo Raić-Malić, Silvana |
author_facet | Meščić, Andrijana Krištafor, Svjetlana Novaković, Ivana Osmanović, Amar Müller, Ursina Završnik, Davorka Ametamey, Simon M. Scapozza, Leonardo Raić-Malić, Silvana |
author_sort | Meščić, Andrijana |
collection | PubMed |
description | The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields in comparison to those obtained by method B using sylilation reaction. The phosphorylation assays of novel compounds as potential substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK) showed that solely pyrimidine 5-substituted acyclonucleosides with a penciclovir-like side chain acted as a fraudulent substrates of HSV-1 TK. Moreover, the uracil derivative with penciclovir-like side chain with less bulky 2-hydroxyethyl substituent at C-5 proved to be a better substrate than the corresponding one with a 3-hydroxypropyl substituent. Therefore, this acyclonucleoside was selected as a lead compound for the development of a positron emission tomography HSV-1 TK activity imaging agent. |
format | Online Article Text |
id | pubmed-6270122 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-62701222018-12-14 C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation Meščić, Andrijana Krištafor, Svjetlana Novaković, Ivana Osmanović, Amar Müller, Ursina Završnik, Davorka Ametamey, Simon M. Scapozza, Leonardo Raić-Malić, Silvana Molecules Article The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields in comparison to those obtained by method B using sylilation reaction. The phosphorylation assays of novel compounds as potential substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK) showed that solely pyrimidine 5-substituted acyclonucleosides with a penciclovir-like side chain acted as a fraudulent substrates of HSV-1 TK. Moreover, the uracil derivative with penciclovir-like side chain with less bulky 2-hydroxyethyl substituent at C-5 proved to be a better substrate than the corresponding one with a 3-hydroxypropyl substituent. Therefore, this acyclonucleoside was selected as a lead compound for the development of a positron emission tomography HSV-1 TK activity imaging agent. MDPI 2013-05-02 /pmc/articles/PMC6270122/ /pubmed/23644977 http://dx.doi.org/10.3390/molecules18055104 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/). |
spellingShingle | Article Meščić, Andrijana Krištafor, Svjetlana Novaković, Ivana Osmanović, Amar Müller, Ursina Završnik, Davorka Ametamey, Simon M. Scapozza, Leonardo Raić-Malić, Silvana C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation |
title | C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation |
title_full | C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation |
title_fullStr | C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation |
title_full_unstemmed | C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation |
title_short | C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation |
title_sort | c-5 hydroxyethyl and hydroxypropyl acyclonucleosides as substrates for thymidine kinase of herpes simplex virus type 1 (hsv-1 tk): syntheses and biological evaluation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6270122/ https://www.ncbi.nlm.nih.gov/pubmed/23644977 http://dx.doi.org/10.3390/molecules18055104 |
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