title: Synthesis and biological evaluation of novel tert-azido or tert-amino substituted penciclovir analogs.
abstract: 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.
authors.affiliation: Laboratory of Medicinal Chemistry, College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Hea Ok
authors.initials: HO
authors.lastname: Kim
authors.forename: Hye Won
authors.initials: HW
authors.lastname: Baek
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Dae-Kee
authors.initials: DK
authors.lastname: Kim
authors.forename: Moon Woo
authors.initials: MW
authors.lastname: Chun
authors.forename: Lak Shin
authors.initials: LS
authors.lastname: Jeong
mesh_terms: 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
chemical_list: D000588:Amines; D000998:Antiviral Agents; D001386:Azides; C053539:penciclovir; D006147:Guanine; D000212:Acyclovir