Journal of medicinal chemistry · 2005
Synthesis and structure-activity-relationships of 1H-imidazo[4,5-c]quinolines that induce interferon production.
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Gerster John F, Lindstrom Kyle J, Miller Richard L, Tomai Mark A, Birmachu Woubalem, Bomersine Shannon N, Gibson Shiela J, Imbertson Linda M, Jacobson Joel R, Knafla Roy T, Maye Peter V, Nikolaides Nickolas, Oneyemi Folakemi Y, Parkhurst Gwen J, Pecore Sharon E, Reiter Michael J, Scribner Lisa S, Testerman Tracy L, Thompson Natalie J, Wagner Tammy L, Weeks Charles E, Andre Jean-Denis, Lagain Daniel, Bastard Yvon, Lupu Michel
Аннотация
1H-Imidazo-[4,5-c]quinolines were prepared while investigating novel nucleoside analogues as potential antiviral agents. While these compounds showed no direct antiviral activity when tested in a number of cell culture systems, some demonstrated potent inhibition of virus lesion development in an intravaginal guinea pig herpes simplex virus-2 assay. We have determined that the in vivo antiviral activity can be attributed to the ability of these molecules to induce the production of cytokines, especially interferon (IFN), in this model. Subsequently, we found that the compounds also induce in vitro production of IFN in human peripheral blood mononuclear cells (hPBMCs). The in vitro results reported herein and the in vivo results reported previously led to the discovery of imiquimod, 26, which was developed as a topical agent and has been approved for the treatment of genital warts, actinic keratosis, and superficial basal cell carcinoma.