Synthesis of novel 3'-hydroxymethyl 5'-deoxythreosyl phosphonic acid nucleoside analogues as potent antiviral agents.
A very efficient synthetic route to novel 3'-hydroxymethyl 5'-deoxythreosyl phosphonic acid nucleosides was described. The discovery of threosyl phosphonate nucleoside (PMDTA, EC(50) = 2.53 μM) as a potent antihuman immunodeficiency virus (anti-HIV) agent has led to the synthesis and biological evaluation of 3'-modified 5'-deoxy versions of the threosyl phosphonate nucleosides. 3'-Hydroxymethyl 5 '-deoxythreosyl phosphonic acid nucleoside analogues 15, 19, 24, and 28 were synthesized from 1,3-dihydroxyacetone and tested for anti-HIV activity as well as cytotoxicity. The adenine analogue 19 exhibits moderate in vitro anti-HIV-1 activity (EC(50) = 10.2 μM).
BK-21 Project Team, College of Pharmacy, Chosun University, Kwangju, Republic of Korea.
Guang Huan
GH
Shen
Lien
L
Kang
Eunae
E
Kim
Joon Hee
JH
Hong
D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006151:Guanosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D010757:Phosphorous Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D014709:Vero Cells
D019380:Anti-HIV Agents; D010757:Phosphorous Acids; D006151:Guanosine