title: Inhibition of HIV-1 capsid assembly: optimization of the antiviral potency by site selective modifications at N1, C2 and C16 of a 5-(5-furan-2-yl-pyrazol-1-yl)-1H-benzimidazole scaffold.
abstract: A uHTS campaign led to the discovery of a 5-(5-furan-2-ylpyrazol-1-yl)-1H-benzimidazole series that inhibits assembly of HIV-1 capsid. Synthetic manipulations at N1, C2 and C16 positions improved the antiviral potency by a . The X-ray structure of 33 complexed with the capsid N-terminal domain allowed identification of major interactions between the inhibitor and the protein.
authors.affiliation: Boehringer Ingelheim (Canada) Ltd, Research & Development, Laval, Québec, Canada H7S 2G5. martin.tremblay@boehringer-ingelheim.com
authors.forename: Martin
authors.initials: M
authors.lastname: Tremblay
authors.forename: Pierre
authors.initials: P
authors.lastname: Bonneau
authors.forename: Yves
authors.initials: Y
authors.lastname: Bousquet
authors.forename: Patrick
authors.initials: P
authors.lastname: DeRoy
authors.forename: Jianmin
authors.initials: J
authors.lastname: Duan
authors.forename: Martin
authors.initials: M
authors.lastname: Duplessis
authors.forename: Alexandre
authors.initials: A
authors.lastname: Gagnon
authors.forename: Michel
authors.initials: M
authors.lastname: Garneau
authors.forename: Nathalie
authors.initials: N
authors.lastname: Goudreau
authors.forename: Ingrid
authors.initials: I
authors.lastname: Guse
authors.forename: Oliver
authors.initials: O
authors.lastname: Hucke
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Kawai
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Lemke
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Mason
authors.forename: Bruno
authors.initials: B
authors.lastname: Simoneau
authors.forename: Simon
authors.initials: S
authors.lastname: Surprenant
authors.forename: Steve
authors.initials: S
authors.lastname: Titolo
authors.forename: Christiane
authors.initials: C
authors.lastname: Yoakim
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D036022:Capsid Proteins / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D015497:HIV-1 / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: C581073:5-(5-furan-2-yl-pyrazol-1-yl)-1H-benzimidazole; D000998:Antiviral Agents; D001562:Benzimidazoles; D036022:Capsid Proteins