Study of different substituted cyclic and acyclic benzylpronucleotides of d4T relative to their hydrolytic stability and antiviral activity.
CycloSal-d4TMP and two different bis(benzyl) phosphate triesters of the antivirally active nucleoside analog d4T were studied with regard to their chemical hydrolysis behavior at pH 7.3, in CEM/0 cell extracts, and their anti-HIV activity. In contrast to triesters 2-4, bis-(o-AB)-d4TMP 1 was found to be chemically exquisitely stable. All compounds led to the formation of d4TMP in cell extracts and all triesters achieved the TK-bypass.
Muus
U
U
Institute of Organic Chemistry, University of Hamburg, Hamburg, Germany. muus@chemie.uni-hamburg.de
De Clercq
E
E
Balzarini
J
J
Naesens
L
L
Meier
C
C
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001593:Benzyl Compounds; D054306:Dideoxynucleotides; D015195:Drug Design; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D018119:Stavudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured
C113124:2',3'-dideoxy-2',3'-didehydrothymidine monophosphate; D019380:Anti-HIV Agents; D000998:Antiviral Agents; D001593:Benzyl Compounds; D054306:Dideoxynucleotides; D018119:Stavudine