title: Novel nevirapine-like inhibitors with improved activity against NNRTI-resistant HIV: 8-heteroarylthiomethyldipyridodiazepinone derivatives.
abstract: A series of 8-heteroarylthiomethyldipyridodiazepinone derivatives were prepared and evaluated for their antiviral profile against wild type virus and the important K103N/Y181C mutant as an indicator for broad activity. 2,6-Dimethylpyridine derivative 16 was found to have a good pharmacokinetic profile in spite of poor metabolic stability in rat liver microsomes.
authors.affiliation: Department of Chemistry, Boehringer Ingelheim (Canada) Ltd, Research & Development, 2100 Cunard Street, Laval, Québec, Canada H7S 2G5. cyoakim@lav.boehringer-ingelheim.com
authors.forename: C
authors.initials: C
authors.lastname: Yoakim
authors.forename: P R
authors.initials: PR
authors.lastname: Bonneau
authors.forename: R
authors.initials: R
authors.lastname: Déziel
authors.forename: L
authors.initials: L
authors.lastname: Doyon
authors.forename: J
authors.initials: J
authors.lastname: Duan
authors.forename: I
authors.initials: I
authors.lastname: Guse
authors.forename: S
authors.initials: S
authors.lastname: Landry
authors.forename: E
authors.initials: E
authors.lastname: Malenfant
authors.forename: J
authors.initials: J
authors.lastname: Naud
authors.forename: W W
authors.initials: WW
authors.lastname: Ogilvie
authors.forename: J A
authors.initials: JA
authors.lastname: O'Meara
authors.forename: R
authors.initials: R
authors.lastname: Plante
authors.forename: B
authors.initials: B
authors.lastname: Simoneau
authors.forename: B
authors.initials: B
authors.lastname: Thavonekham
authors.forename: M
authors.initials: M
authors.lastname: Bös
authors.forename: M G
authors.initials: MG
authors.lastname: Cordingley
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D001381:Azepines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000737:chemistry; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008657:Metabolic Clearance Rate; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009154:Mutation; D019829:Nevirapine / Q000138:chemical synthesis* / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D001381:Azepines; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D054303:HIV Reverse Transcriptase; C023666:pyridine