Synthesis and biological evaluation of novel tert-azido or tert-amino substituted penciclovir analogs.
tert-Azido or amino substituted penciclovir analogs, 1-3 were synthesized for the purpose of improving the efficacy and bioavailability of penciclovir and searching for novel antiviral agents. Among several methods attempted to insert an azido group into the alpha,beta-unsaturated ester 6, only Bronsted acid-catalysed 1,4-conjugate addition conditions (NaN3, 75% acetic acid, 80 degrees C) gave the desired tert-azido product 7. The synthesized final penciclovir analogs 1-3 were evaluated in vitro against several viruses such as HIV-1, HSV-1 and 2, poliovirus, VZV, and VSV. Compound 2 only showed weak antiviral activity against HSV-1 without cytotoxicity. Although the synthesized compounds did not exhibit an excellent antiviral activity, the successful method used in introducing the tert-azido group is expected to be generally utilized for the synthesis of nucleoside analogs with a tert-azido substituent.
Kim
Hea Ok
HO
Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
Baek
Hye Won
HW
Moon
Hyung Ryong
HR
Kim
Dae-Kee
DK
Chun
Moon Woo
MW
Jeong
Lak Shin
LS
D000212:Acyclovir / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000588:Amines / Q000737:chemistry*; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001386:Azides / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D002460:Cell Line; D006147:Guanine; D015497:HIV-1 / Q000187:drug effects; D015498:HIV-2 / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D017955:Poliovirus / Q000187:drug effects; D018139:Simplexvirus / Q000187:drug effects
D000588:Amines; D000998:Antiviral Agents; D001386:Azides; C053539:penciclovir; D006147:Guanine; D000212:Acyclovir