Uncharged AZT and D4T derivatives of phosphonoformic and phosphonoacetic acids as anti-HIV pronucleosides.
Two series of new lipophilic phosphonoformate and phosphonoacetate derivatives of AZT and d4T were synthesized and evaluated as anti-HIV agents. The efficacy of some of the synthesized compounds in cell cultures infected with HIV-1 was higher than that of the parent nucleosides and only slightly correlated to their stability in the phosphate buffer and human blood serum. The synthesized phosphonates are most probably prodrug forms of the corresponding nucleosides.
Shirokova
Elena A
EA
Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 32 Vavilov str., Moscow 119991, Russian Federation. shirokova-elena@list.ru
Jasko
Maxim V
MV
Khandazhinskaya
Anastasiya L
AL
Ivanov
Alexander V
AV
Yanvarev
Dmitry V
DV
Skoblov
Yury S
YS
Mitkevich
Vladimir A
VA
Bocharov
Eduard V
EV
Pronyaeva
Tatyana R
TR
Fedyuk
Nina V
NV
Kukhanova
Marina K
MK
Pokrovsky
Andrey G
AG
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D004355:Drug Stability; D017245:Foscarnet / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D006868:Hydrolysis; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D018119:Stavudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
D019380:Anti-HIV Agents; D011355:Prodrugs; D017245:Foscarnet; D015215:Zidovudine; D018119:Stavudine; D010746:Phosphonoacetic Acid