Novel 8-substituted dipyridodiazepinone inhibitors with a broad-spectrum of activity against HIV-1 strains resistant to non-nucleoside reverse transcriptase inhibitors.
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.
O'Meara
Jeff A
JA
Boehringer Ingelheim (Canada) Ltd., Research & Development, 2100 Cunard Street, Laval, Québec, Canada H7S 2G5.
Yoakim
Christiane
C
Bonneau
Pierre R
PR
Bös
Michael
M
Cordingley
Michael G
MG
Déziel
Robert
R
Doyon
Louise
L
Duan
Jianmin
J
Garneau
Michel
M
Guse
Ingrid
I
Landry
Serge
S
Malenfant
Eric
E
Naud
Julie
J
Ogilvie
William W
WW
Thavonekham
Bounkham
B
Simoneau
Bruno
B
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
D019380:Anti-HIV Agents; D001381:Azepines; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors