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Discovery and optimization of potent broad-spectrum arenavirus inhibitors derived from benzimidazole and related heterocycles.

Abstract：

:A series of potent arenavirus inhibitors sharing a benzimidazole core were previously reported by our group. SAR studies were expanded beyond the previous analysis, which involved the attached phenyl rings and methylamino linker portion, to include modifications focused on the benzimidazole core. These changes included the introduction of various substituents to the bicyclic benzimidazole ring system along with alternate core heterocycles. Many of the analogs containing alternate nitrogen-based bicyclic ring systems were found to retain antiviral potency compared to the benzimidazole series from which we derived our lead compound, ST-193. In fact, 21 h, built on an imidazopyridine core, possessed a near tenfold increase in potency against Lassa virus pseudotypes compared to ST-193. As found with the benzimidazole series, broad-spectrum arenavirus activity was also observed for a number of the analogs discovered during this study.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Burgeson JR,Moore AL,Gharaibeh DN,Larson RA,Cerruti NR,Amberg SM,Hruby DE,Dai D

doi

10.1016/j.bmcl.2012.11.093

subject

Has Abstract

pub_date

2013-02-01 00:00:00

pages

750-6

issue

3

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(12)01545-4

journal_volume

23

pub_type

杂志文章

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