title: 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.
authors.affiliation: SIGA Technologies, Inc., 4575 SW Research Way, Suite 230, Corvallis, OR 97333, USA.
authors.forename: James R
authors.initials: JR
authors.lastname: Burgeson
authors.forename: Amy L
authors.initials: AL
authors.lastname: Moore
authors.forename: Dima N
authors.initials: DN
authors.lastname: Gharaibeh
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Larson
authors.forename: Natasha R
authors.initials: NR
authors.lastname: Cerruti
authors.forename: Sean M
authors.initials: SM
authors.lastname: Amberg
authors.forename: Dennis E
authors.initials: DE
authors.lastname: Hruby
authors.forename: Dongcheng
authors.initials: D
authors.lastname: Dai
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018050:Arenavirus / Q000187:drug effects*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055808:Drug Discovery; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007836:Lassa virus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D001562:Benzimidazoles; D006571:Heterocyclic Compounds; C581846:ST-193