title: Synthesis and anti-HIV activity of cyclic pyrimidine phosphonomethoxy nucleosides and their prodrugs: a comparison of phosphonates and corresponding nucleosides.
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: Gilead Sciences, Inc., Foster City, California 94404, USA. rmackman@gilead.com
authors: Richard L
authors: RL
authors: Mackman
authors: Lijun
authors: L
authors: Zhang
authors: Vidya
authors: V
authors: Prasad
authors: Constantine G
authors: CG
authors: Boojamra
authors: James
authors: J
authors: Chen
authors: Janet
authors: J
authors: Douglas
authors: Deborah
authors: D
authors: Grant
authors: Genevieve
authors: G
authors: Laflamme
authors: Hon
authors: H
authors: Hui
authors: Choung U
authors: CU
authors: Kim
authors: Jay
authors: J
authors: Parrish
authors: Antitsa D
authors: AD
authors: Stoycheva
authors: Swami
authors: S
authors: Swaminathan
authors: KeYu
authors: K
authors: Wang
authors: Tomas
authors: T
authors: Cihlar
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization / Q000187:drug effects; D024882:Drug Resistance, Viral / Q000187:drug effects; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D063065:Organophosphonates / Q000138:chemical synthesis* / Q000737:chemistry; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015215:Zidovudine / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D009705:Nucleosides; D063065:Organophosphonates; D011355:Prodrugs; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine