1. SAR analysis of a series of acylthiourea derivatives possessing broad-spectrum antiviral activity.
- Author
-
Burgeson JR, Moore AL, Boutilier JK, Cerruti NR, Gharaibeh DN, Lovejoy CE, Amberg SM, Hruby DE, Tyavanagimatt SR, Allen RD 3rd, and Dai D
- Subjects
- Antiviral Agents chemical synthesis, Antiviral Agents pharmacology, Arenavirus drug effects, Dengue Virus drug effects, La Crosse virus drug effects, Orthomyxoviridae drug effects, Structure-Activity Relationship, Thiourea chemical synthesis, Thiourea pharmacology, Vaccinia virus drug effects, Antiviral Agents chemistry, Thiourea chemistry
- Abstract
A series of acylthiourea derivatives were designed, synthesized, and evaluated for broad-spectrum antiviral activity with selected viruses from Poxviridae (vaccinia virus) and two different genera of the family Bunyaviridae (Rift Valley fever and La Crosse viruses). A compound selected from a library screen, compound 1, displayed submicromolar antiviral activity against both vaccinia virus (EC(50)=0.25 μM) and La Crosse virus (EC(50)=0.27 μM) in cytopathic effect (CPE) assays. SAR analysis was performed to further improve antiviral potency and to optimize drug-like properties of the initial hits. During our analysis, we identified 26, which was found to be nearly fourfold more potent than 1 against both vaccinia and La Crosse viruses. Selected compounds were further tested to more fully characterize the spectrum of antiviral activity. Many of these possessed single digit micromolar and sub-micromolar antiviral activity against a diverse array of targets, including influenza virus (Orthomyxoviridae), Tacaribe virus (Arenaviridae), and dengue virus (Flaviviridae)., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF