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Design and synthesis of potential ribonucleotide reductase enzyme (RNR) inhibitors as antileukemic and/or antiviral 2′-deoxymethylene nucleosides
- Source :
- Future Journal of Pharmaceutical Sciences, Vol 1, Iss 2, Pp 42-49 (2015)
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- In order to improve the antitumor and/or antiviral activities of existing nucleoside analogs, eight new compounds (9a,b, 14a,b, 15a,b and 16a,b) were designed and synthesized. Halogen atom were incorporated at the 2-position of the purine base to render the amino group at the 6-position less susceptible to metabolism by adenosine deaminase. A methylene group was introduced at the 2′-position following the lead of nucleoside antibiotics angustmycin A and neplanocin A. The two key intermediates 9a and 9b were prepared from guanosine after protection of the 3′ and 5′ hydroxyl groups and oxidation of the 2′ hydroxyl group to the corresponding carbonyl group using swern method. The conversion of the carbonyl group to the methylene function was carried out by applying wittig reaction conditions. The final compounds 14a,b, 15a,b, 16a,b were prepared by means of nonaqueous diazotization of 9a and 9b. The prepared compounds were subjected to in vitro antileukemic and antiviral activity upon a new L1210 cell line that is doubly resistant to both hydroxyurea and deoxyadenosine which was grown and characterized. The new compounds showed potent antileukemic activity.
- Subjects :
- Ribonucleotide
biology
Stereochemistry
Antileukemic
lcsh:RM1-950
lcsh:RS1-441
Guanosine
lcsh:Pharmacy and materia medica
Ribonucleotide reductase enzyme (RNR) inhibitors
chemistry.chemical_compound
Anticancer
lcsh:Therapeutics. Pharmacology
Ribonucleotide reductase
Adenosine deaminase
Deoxyadenosine
chemistry
Wittig reaction
Swern oxidation
biology.protein
Antiviral
Nucleoside
Subjects
Details
- ISSN :
- 23147245
- Volume :
- 1
- Database :
- OpenAIRE
- Journal :
- Future Journal of Pharmaceutical Sciences
- Accession number :
- edsair.doi.dedup.....5557d19397c59844deafd4f651137e8f