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New HSV-1 Anti-Viral 1′-Homocarbocyclic Nucleoside Analogs with an Optically Active Substituted Bicyclo[2.2.1]Heptane Fragment as a Glycoside Moiety
- Source :
- Molecules, Vol 24, Iss 13, p 2446 (2019), Molecules, Volume 24, Issue 13
- Publication Year :
- 2019
- Publisher :
- MDPI AG, 2019.
-
Abstract
- New 1&prime<br />homocarbanucleoside analogs with an optically active substituted bicyclo[2.2.1]heptane skeleton as sugar moiety were synthesized. The pyrimidine analogs with uracil, 5-fluorouracil, thymine and cytosine and key intermediate with 6-chloropurine (5) as nucleobases were synthesized by a selective Mitsunobu reaction on the primary hydroxymethyl group in the presence of 5-endo-hydroxyl group. Adenine and 6-substituted adenine homonucleosides were obtained by the substitution of the 6-chlorine atom of the key intermediate 5 with ammonia and selected amines, and 6-methoxy- and 6-ethoxy substituted purine homonucleosides by reaction with the corresponding alkoxides. No derivatives appeared active against entero, yellow fever, chikungunya, and adeno type 1viruses. Two compounds (6j and 6d) had lower IC50 (15 &plusmn<br />2 and 21 &plusmn<br />4 &micro<br />M) and compound 6f had an identical value of IC50 (28 &plusmn<br />M) to that of acyclovir, suggesting that the bicyclo[2.2.1]heptane skeleton could be further studied to find a candidate for sugar moiety of the nucleosides.
- Subjects :
- herpesviruses
Molecular Conformation
Pharmaceutical Science
Ligands
01 natural sciences
6-substituted adenine nucleosides
Analytical Chemistry
Nucleobase
chemistry.chemical_compound
Drug Discovery
Moiety
Hydroxymethyl
Glycosides
1′-homocarbonucleosides
Molecular Structure
Bicyclic molecule
Nucleosides
Molecular Docking Simulation
Chemistry (miscellaneous)
antiviral activity
Molecular Medicine
Mitsunobu reaction
Cytosine
Stereochemistry
Microbial Sensitivity Tests
Molecular Dynamics Simulation
010402 general chemistry
Antiviral Agents
Article
Heptanes
lcsh:QD241-441
Structure-Activity Relationship
molecular docking
lcsh:Organic chemistry
Humans
bicyclo[2.2.1]heptane nucleosides
Physical and Theoretical Chemistry
6-chloropurine
010405 organic chemistry
Spectrum Analysis
Organic Chemistry
Uracil
0104 chemical sciences
Thymine
chemistry
Purines
Drug Design
Sugars
Subjects
Details
- Language :
- English
- ISSN :
- 14203049
- Volume :
- 24
- Issue :
- 13
- Database :
- OpenAIRE
- Journal :
- Molecules
- Accession number :
- edsair.doi.dedup.....47f4fbc6620ba5a686461703830a23a9