Design and synthesis of novel 1',3'-dioxolane 5'-deoxyphosphonic acid purine analogues as potent antiviral agents.
Electronic parameters of 1',3 '-oxygen play significant roles in steering the conformation of nucleoside phosphonic acid analogues. To investigate the relationship of two oxygen atoms with antiviral enhancement, novel 1',3 '-dioxolane 5 '-deoxyphosphonic acid purine analogues were synthesized via de novo acyclic stereoselective route from acrolein and glycolic acid. The synthesized nucleoside phosphonic acid analogues 14 and 19 were subjected to antiviral screening against several viruses, such as HIV-1, HSV-1, HSV-2, and HCMV. The guanine analogue 19 exhibits in vitro anti-HIV-1 activity similar to that of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) in MT-4 cells.
College of Pharmacy, Chosun University, Dong-gu, Kwangju, Republic of Korea.
Eunae
E
Kim
Lian Jin
LJ
Liu
Wonjae
W
Lee
Joon Hee
JH
Hong
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003587:Cytomegalovirus / Q000187:drug effects; D004148:Dioxolanes / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006150:Guanine Nucleotides / Q000737:chemistry* / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000187:drug effects; D018258:Herpesvirus 2, Human / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C572556:9-(((2-ethyl(1,3)dioxolan-4-yl)guanine))phosphonic acid; D000998:Antiviral Agents; D004148:Dioxolanes; D006150:Guanine Nucleotides