| 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 |
| Authors: |
Silvana Raić-Malić, Simon M. Ametamey, Leonardo Scapozza, Davorka Završnik, Ursina Müller, Amar Osmanović, Ivana Novaković, Svjetlana Krištafor, Andrijana Meščić |
| Source: |
Molecules, Vol 18, Iss 5, Pp 5104-5124 (2013) |
| Publisher Information: |
MDPI AG, 2013. |
| Publication Year: |
2013 |
| Collection: |
LCC:Organic chemistry |
| Subject Terms: |
acyclic nucleoside analogues, 5-substituted pyrimidines, herpes simplex virus type 1 thymidine kinase (HSV-1 TK), positron emission tomography (PET), Organic chemistry, QD241-441 |
| More Details: |
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. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1420-3049 |
| Relation: |
http://www.mdpi.com/1420-3049/18/5/5104; https://doaj.org/toc/1420-3049 |
| DOI: |
10.3390/molecules18055104 |
| Access URL: |
https://doaj.org/article/7e6d1abd87ac407bb52c113da0322b20 |
| Accession Number: |
edsdoj.7e6d1abd87ac407bb52c113da0322b20 |
| Database: |
Directory of Open Access Journals |
