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Lead optimization of an acylhydrazone scaffold possessing antiviral activity against Lassa virus.

Abstract：

:Previously we reported the optimization of antiviral scaffolds containing benzimidazole and related heterocycles possessing activity against a variety of arenaviruses. These series of compounds were discovered through an HTS campaign of a 400,000 small molecule library using lentivirus-based pseudotypes incorporated with the Lassa virus envelope glycoprotein (LASV GP). This screening also uncovered an alternate series of very potent arenavirus inhibitors based upon an acylhydrazone scaffold. Subsequent SAR analysis of this chemical series involved various substitutions throughout the chemical framework along with assessment of the preferred stereochemistry. These studies led to an optimized analog (ST-161) possessing subnanomolar activity against LASV and submicromolar activity against a number of other viruses in the Arenaviridae family.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Burgeson JR,Gharaibeh DN,Moore AL,Larson RA,Amberg SM,Bolken TC,Hruby DE,Dai D

doi

10.1016/j.bmcl.2013.08.103

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

5840-3

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(13)01052-4

journal_volume

23

pub_type

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