Design, synthesis, and biological evaluation of novel iso-D-2',3'-dideoxy-3'-fluorothianucleoside derivatives.
Novel iso-d-2',3'-dideoxythianucleoside derivatives 1-4 were designed and asymmetrically synthesized as a bioisostere of lamivudine to search for new anti-HIV agents. The information about using sulfur participation occurred on DAST fluorination and Mitsunobu reaction will be of great help in synthesizing sulfur-containing compounds. Final compounds 1-4 were evaluated against HIV-1 and 2, HSV-1 and 2, EMCV, Cox. B3, VSV, FluA (Taiwan), FluA (Johan.), FCV, and FIP. Only cytosine analogue 3 showed a potent anti-VSV activity (EC(50)=9.43microg/mL). This result implies that iso-2',3'-dideoxy sugar templates might play a role of a sugar surrogate of nucleosides for the development of anti-RNA virus agent.
Kim
Kyung Ran
KR
Laboratory of Medicinal Chemistry, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 609-735, Republic of Korea.
Moon
Hyung Ryong
HR
Park
Ah-Young
AY
Chun
Moon Woo
MW
Jeong
Lak Shin
LS
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D004686:Encephalomyocarditis virus / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects*; D015498:HIV-2 / Q000187:drug effects*; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D007094:Imides / Q000138:chemical synthesis* / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D010569:Perylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects*
D000998:Antiviral Agents; D007094:Imides; C517085:perylenetetracarboxylic diimide; D010569:Perylene