title: Thiotetrazole alkynylacetanilides as potent and bioavailable non-nucleoside inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases.
abstract: A series of aryl thiotetrazolylacetanilides were synthesized and found to be potent inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases. The incorporation of an alkynyl fragment on the aniline provided inhibitors with excellent cellular activity and extensive SAR led to the identification of one inhibitor having good oral bioavailability in rats.
authors.affiliation: Boehringer Ingelheim (Canada) Ltd., Research and Development, 2100 Cunard Street, Laval, Que., Canada, H7S 2G5. agagnon@lav.boehringer-ingelheim.com
authors.forename: Alexandre
authors.initials: A
authors.lastname: Gagnon
authors.forename: Ma'an H
authors.initials: MH
authors.lastname: Amad
authors.forename: Pierre R
authors.initials: PR
authors.lastname: Bonneau
authors.forename: René
authors.initials: R
authors.lastname: Coulombe
authors.forename: Patrick L
authors.initials: PL
authors.lastname: DeRoy
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: Araz
authors.initials: A
authors.lastname: Jakalian
authors.forename: Eric
authors.initials: E
authors.lastname: Jolicoeur
authors.forename: Serge
authors.initials: S
authors.lastname: Landry
authors.forename: Eric
authors.initials: E
authors.lastname: Malenfant
authors.forename: Bruno
authors.initials: B
authors.lastname: Simoneau
authors.forename: Christiane
authors.initials: C
authors.lastname: Yoakim
mesh_terms: D000083:Acetanilides / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001682:Biological Availability; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics*; D008958:Models, Molecular; D015394:Molecular Structure; D009154:Mutation; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000083:Acetanilides; D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase