Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: a comparison of phosphonates and corresponding nucleosides.
Journal: Nucleosides, Nucleotides & Nucleic Acids
Published:
Abstract
Cyclic phosphonomethoxy pyrimidine nucleosides that are bioisosteres of the monophosphate metabolites of HIV reverse transcriptase (RT) inhibitors AZT, d4T, and ddC have been synthesized. The RT inhibitory activities of the phosphonates were reduced for both dideoxy (dd) and dideoxydidehydro (d4) analogs compared to the nucleosides. Bis-isopropyloxymethylcarbonyl (BisPOC) prodrugs were prepared on selected compounds and provided > 150-fold improvements in antiviral activity.
Authors
Richard Mackman, Lijun Zhang, Vidya Prasad, Constantine Boojamra, James Chen, Janet Douglas, Deborah Grant, Genevieve Laflamme, Hon Hui, Choung Kim, Jay Parrish, Antitsa Stoycheva, Swami Swaminathan, Keyu Wang, Tomas Cihlar