TY - JOUR
T1 - In vitro anti-human immunodeficiency virus activities of Z- and E- methylenecyclopropane nucleoside analogues and their phosphoro-L-alaninate diesters
AU - Uchida, Hiroyuki
AU - Kodama, Eiichi N.
AU - Yoshimura, Kazuhisa
AU - Maeda, Yosuke
AU - Kosalaraksa, Pope
AU - Maroun, Victor
AU - Qiu, Yao Ling
AU - Zemlicka, Jiri
AU - Mitsuya, Hiroaki
PY - 1999/6
Y1 - 1999/6
N2 - 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 μM, 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.
AB - 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 μM, 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.
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U2 - 10.1128/aac.43.6.1487
DO - 10.1128/aac.43.6.1487
M3 - Article
C2 - 10348777
AN - SCOPUS:0033026673
VL - 43
SP - 1487
EP - 1490
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 6
ER -