Design and synthesis of acyclic nucleoside analogs with chlorinated imidazo[1,2-a]pyridine bases.
A series of acyclic C-nucleoside analogs of 2,6-dichloro- and 2,6,7-trichloroimidazo[1,2-a]pyridine were synthesized and tested for antiviral activity. The appropriate hydroxymethyl-substituted heterocycles were treated successively with thionyl chloride, an appropriate nucleophile, then diisopropylethylamine to obtain the desired acyclic nucleoside analogs. These compounds were evaluated for activity against human cytomegalovirus and herpes simplex virus, type 1. Two of the dichloro analogs, but none of the trichloro analogs demonstrated slight antiviral activity (IC50's = 20-45 microM) at non-cytotoxic concentrations.
Williams
John D
JD
Department of Medicinal Chemistry, College of Pharmacy, University of Michigan, Ann Arbor, Michigan 48019-1065, USA.
Mourad
Alaa E
AE
Drach
John C
JC
Townsend
Leroy B
LB
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D002460:Cell Line; D002713:Chlorine / Q000737:chemistry*; D003587:Cytomegalovirus / Q000187:drug effects / Q000502:physiology; D015195:Drug Design; D004797:Enzyme-Linked Immunosorbent Assay; D018259:Herpesvirus 1, Human / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009711:Nucleotides / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D009711:Nucleotides; D011725:Pyridines; C017579:nucleoside 3',5'-biphosphates; D002713:Chlorine; C001439:imidazo(1,2-a)pyridine