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Novel 8-substituted dipyridodiazepinone inhibitors with a broad-spectrum of activity against HIV-1 strains resistant to non-nucleoside reverse transcriptase inhibitors. 2005
Jeff A O'Meara, and
Christiane Yoakim, and
Pierre R Bonneau, and
Michael Bös, and
Michael G Cordingley, and
Robert Déziel, and
Louise Doyon, and
Jianmin Duan, and
Michel Garneau, and
Ingrid Guse, and
Serge Landry, and
Eric Malenfant, and
Julie Naud, and
William W Ogilvie, and
Bounkham Thavonekham, and
Bruno Simoneau
Boehringer Ingelheim (Canada) Ltd., Research & Development, 2100 Cunard Street, Laval, Québec, Canada H7S 2G5.
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.
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