title: Novel 8-substituted dipyridodiazepinone inhibitors with a broad-spectrum of activity against HIV-1 strains resistant to non-nucleoside reverse transcriptase inhibitors.
abstract: A series of novel 8-substituted dipyridodiazepinone-based inhibitors were investigated for their antiviral activity against wild type human immunodeficiency virus (HIV-1) and the clinically prevalent K103N/Y181C mutant virus. Our efforts have resulted in a series of benzoic acid analogues that are potent inhibitors of HIV-1 replication against a panel of HIV-1 strains resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIs). Furthermore, the combination of good antiviral potency, a broad spectrum of activity, and an excellent pharmacokinetic profile provides strong justification for the further development of compound (7) as a potential treatment for wild type and NNRTI-resistant HIV-1 infection.
authors.affiliation: Boehringer Ingelheim (Canada) Ltd., Research & Development, 2100 Cunard Street, Laval, Québec, Canada H7S 2G5.
authors.forename: Jeff A
authors.initials: JA
authors.lastname: O'Meara
authors.forename: Christiane
authors.initials: C
authors.lastname: Yoakim
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Bonneau
authors.forename: Michael
authors.initials: M
authors.lastname: Bös
authors.forename: Michael G
authors.initials: MG
authors.lastname: Cordingley
authors.forename: Robert
authors.initials: R
authors.lastname: Déziel
authors.forename: Louise
authors.initials: L
authors.lastname: Doyon
authors.forename: Jianmin
authors.initials: J
authors.lastname: Duan
authors.forename: Michel
authors.initials: M
authors.lastname: Garneau
authors.forename: Ingrid
authors.initials: I
authors.lastname: Guse
authors.forename: Serge
authors.initials: S
authors.lastname: Landry
authors.forename: Eric
authors.initials: E
authors.lastname: Malenfant
authors.forename: Julie
authors.initials: J
authors.lastname: Naud
authors.forename: William W
authors.initials: WW
authors.lastname: Ogilvie
authors.forename: Bounkham
authors.initials: B
authors.lastname: Thavonekham
authors.forename: Bruno
authors.initials: B
authors.lastname: Simoneau
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018938:Caco-2 Cells; D004285:Dogs; D024882:Drug Resistance, Viral; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008253:Macaca mulatta; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009154:Mutation; D010539:Permeability; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D001381:Azepines; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors