title: Synthesis, anti-HIV activity, and resistance profiles of ribose modified nucleoside phosphonates.
abstract: A series of nucleoside phosphonate reverse transcriptase (RT) inhibitors have been synthesized and their anti-HIV activity and resistance profiles evaluated. The most potent analog [5-(6-amino-purin-9-yl)-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (d4AP) demonstrated a HIV EC(50)=2.1 microM, and the most favorable resistance profile against HIV-1 variants with K65R, M184V or multiple thymidine analog mutations in RT.
authors.affiliation: Gilead Sciences, Inc., 333 Lakeside Drive, Foster City, CA 94404, USA. rmackman@gilead.com
authors.forename: Richard L
authors.initials: RL
authors.lastname: Mackman
authors.forename: Constantine G
authors.initials: CG
authors.lastname: Boojamra
authors.forename: Vidya
authors.initials: V
authors.lastname: Prasad
authors.forename: Lijun
authors.initials: L
authors.lastname: Zhang
authors.forename: Kuei-Ying
authors.initials: KY
authors.lastname: Lin
authors.forename: Oleg
authors.initials: O
authors.lastname: Petrakovsky
authors.forename: Darius
authors.initials: D
authors.lastname: Babusis
authors.forename: James
authors.initials: J
authors.lastname: Chen
authors.forename: Janet
authors.initials: J
authors.lastname: Douglas
authors.forename: Deborah
authors.initials: D
authors.lastname: Grant
authors.forename: Hon C
authors.initials: HC
authors.lastname: Hui
authors.forename: Choung U
authors.initials: CU
authors.lastname: Kim
authors.forename: David Y
authors.initials: DY
authors.lastname: Markevitch
authors.forename: Jennifer
authors.initials: J
authors.lastname: Vela
authors.forename: Adrian
authors.initials: A
authors.lastname: Ray
authors.forename: Tomas
authors.initials: T
authors.lastname: Cihlar
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006678:HIV / Q000187:drug effects* / Q000235:genetics*; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D063065:Organophosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000068698:Tenofovir
chemical_list: C526695:(5-(6-amino-purin-9-yl)-2,5-dihydrofuran-2-yloxymethyl)phosphonic acid; D019380:Anti-HIV Agents; D009705:Nucleosides; D063065:Organophosphonates; D018894:Reverse Transcriptase Inhibitors; D000068698:Tenofovir; D000225:Adenine