|
|
|
Article info. : 2008; 5(2) (pp 228~237)
|
|
|
 |
 |
 |
|
|
|
|
|
Design, Synthesis, and Antiviral Activity of Novel
Phosphoramidates
F. Valiyeva, F.-Y. Tsaib,*,
A.A. Sabouryd, H.-J. Liua,c, A.A. Moosavi-Movahedid
and G.H. Hakimelahia,d,*
a Institute of Chemistry, Academia Sinica, Taipei
115, Taiwan
bCenter of General Education, Chang Gung University, 259
Wen-Hwa, Kwei-Shan, Taoyuan 333, Taiwan, ROC
cDepartment of Chemistry, National Tsing Hua University,
Hsinchu 300, Taiwan
dInstitute of Biochemistry and Biophysics, University of
Tehran, Tehran, Iran
(Received 3 March 2007, Accepted 12 March 2007)
Novel
phosphoramidates 8a-b possessing structural features similar to
nucleoside phosphonates HPMPA, PMEA, PMEG, and oxathiolane nucleoside
BCH-189 were synthesized by chemical methods. The designed molecules
exhibited significant antiviral activities. We hypothesized that, as a
masked membrane-soluble form of the potential bioactive compounds
7a-b, phosphoramidates 8a-b may act as a proteinase
substrate. Then, the potential drug 7a-b will be liberated inside
the infected cells. The triphosphate anabolites of each could act as
competitive substrates for the HIV reverse transcriptase and terminate
DNA synthesis after being incorporated into the growing DNA strand.
Phosphoramidates 8a-b were synthesized as racemates to allow
access to both enantiomers.
Keywords: Nucleosides, Nucleotides, Phosphoramidates,
Antivirals, Anti-HIV, Oxathiolane |
|
|
 |
|
 |
|
|
|
|
|
|
|
|
|
|
|
