tetano
Editor, Senior Moderator
Bioorg Med Chem Lett. 2012 May 17. [Epub ahead of print]
SAR analysis of a series of acylthiourea derivatives possessing broad-spectrum antiviral activity.
Burgeson JR, Moore AL, Boutilier JK, Cerruti NR, Gharaibeh DN, Lovejoy CE, Amberg SM, Hruby DE, Tyavanagimatt SR, Allen RD 3rd, Dai D.
Source
SIGA Technologies, Inc., 4575 SW Research Way, Suite 230, Corvallis, OR 97333, United States.
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)=0.25μM) and La Crosse virus (EC(50)=0.27μM) 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.
PMID:
22664128
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22664128
SAR analysis of a series of acylthiourea derivatives possessing broad-spectrum antiviral activity.
Burgeson JR, Moore AL, Boutilier JK, Cerruti NR, Gharaibeh DN, Lovejoy CE, Amberg SM, Hruby DE, Tyavanagimatt SR, Allen RD 3rd, Dai D.
Source
SIGA Technologies, Inc., 4575 SW Research Way, Suite 230, Corvallis, OR 97333, United States.
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)=0.25μM) and La Crosse virus (EC(50)=0.27μM) 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.
PMID:
22664128
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/22664128