title: In vitro anti-human immunodeficiency virus activities of Z- and E-methylenecyclopropane nucleoside analogues and their phosphoro-L-alaninate diesters.
abstract: Nucleoside analogues with a Z- or an E-methylenecyclopropane moiety were synthesized and examined for activity against human immunodeficiency virus type 1 (HIV-1) in vitro. The addition of a methyl phenyl phosphoro-L-alaninate moiety to modestly active analogues resulted in potentiation of their anti-HIV-1 activity. Two such compounds, designated QYL-685 (with 2,6-diaminopurine) and QYL-609 (with adenine), were most potent against HIV-1 in vitro, with 50% inhibitory concentrations of 0.034 and 0.0026 microM, respectively, in MT-2 cell-based assays. Both compounds were active against zidovudine-resistant, didanosine-resistant, and multi-dideoxynucleoside-resistant infectious clones in vitro. Further development of these analogues as potential therapies for HIV-1 infection is warranted.
authors.affiliation: The Experimental Retrovirology Section, Department of Developmental Therapeutics, Medicine Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: H
authors.initials: H
authors.lastname: Uchida
authors.forename: E N
authors.initials: EN
authors.lastname: Kodama
authors.forename: K
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Y
authors.initials: Y
authors.lastname: Maeda
authors.forename: P
authors.initials: P
authors.lastname: Kosalaraksa
authors.forename: V
authors.initials: V
authors.lastname: Maroun
authors.forename: Y L
authors.initials: YL
authors.lastname: Qiu
authors.forename: J
authors.initials: J
authors.lastname: Zemlicka
authors.forename: H
authors.initials: H
authors.lastname: Mitsuya
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D009705:Nucleosides / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D009705:Nucleosides