Thiotetrazole alkynylacetanilides as potent and bioavailable non-nucleoside inhibitors of the HIV-1 wild type and K103N/Y181C double mutant reverse transcriptases.
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.
Gagnon
Alexandre
A
Boehringer Ingelheim (Canada) Ltd., Research and Development, 2100 Cunard Street, Laval, Que., Canada, H7S 2G5. agagnon@lav.boehringer-ingelheim.com
Amad
Ma'an H
MH
Bonneau
Pierre R
PR
Coulombe
René
R
DeRoy
Patrick L
PL
Doyon
Louise
L
Duan
Jianmin
J
Garneau
Michel
M
Guse
Ingrid
I
Jakalian
Araz
A
Jolicoeur
Eric
E
Landry
Serge
S
Malenfant
Eric
E
Simoneau
Bruno
B
Yoakim
Christiane
C
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
D000083:Acetanilides; D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase