Hexahydro-pyrrolo- and hexahydro-1H-pyrido[1,2-b]pyridazin-2-ones as potent inhibitors of HCV NS5B polymerase
Graphical abstract
Section snippets
Acknowledgments
The authors thank Drs. Peter Dragovich, Devron Averett and Steve Worland for their support and helpful discussions during the course of this work.
References and notes (17)
- et al.
J. Med. Chem.
(2007)et al.J. Biol. Chem.
(2002)et al.Bioorg. Med. Chem. Lett.
(2006)dBlake, J. F.; Fell, J. B.; Fischer, J. P.; Hendricks, R. T.; Spencer, S. R.; Stengel, P. J. WO2006117306,... et al.Bioorg. Med. Chem. Lett.
(2005)fHutchinson, D. K. et al. U.S. Patent US2005107364,... et al.Bioorg. Med. Chem. Lett.
(2008) - et al.
Bioorg. Med. Chem. Lett.
(2008) - et al.
J. Prakt. Chem.
(1977) - et al.
Pharm. Res.
(1993) - et al.
Science
(1989) Hepatology
(2002)et al.N. Engl. J. Med.
(1999)et al.J. Hepatol.
(2003)- et al.
Science
(1972)et al.Adv. Virus Res.
(1993)
Cited by (17)
Facilitating SARS CoV-2 RNA-Dependent RNA polymerase (RdRp) drug discovery by the aid of HCV NS5B palm subdomain binders: In silico approaches and benchmarking
2021, Computers in Biology and MedicineCitation Excerpt :It is important to mention that irreversible inhibitors were excluded from the set. Collectively, these compounds represent the following scaffold classes: Benzothiadiazine, benzothiazine, 1,1-dioxoisothiazole, 5,6-dihydro-1H-pyridin-2-one, proline sulfonamide, acrylic acid, N-acyl pyrrolidine, benzamide, nicotinamide, anthranilic acid, benzodiazepine, sulphone and benzofuran [18,20–32]. For selecting a protein structure for the benchmarking study, we downloaded the NS5B structures from the PDB (Table S2 in SM).
Bicyclic 6-6 Systems With One Bridgehead (Ring Junction) Nitrogen Atom: One Extra Heteroatom 1:0
2021, Comprehensive Heterocyclic Chemistry IVRecent advances in drug discovery of benzothiadiazine and related analogs as HCV NS5B polymerase inhibitors
2011, Bioorganic and Medicinal ChemistryCitation Excerpt :Although the potency of the series was maintained, poor bioavailability was observed. The best compound of the series 14c exhibited poor bioavailability (%F = 7), potentially due to low intestinal permeability.99 To reduce the PSA, the ring nitrogen of 14 was removed and 5,6-dihydro-1H-pyridine-2-ones of general structure 16 were prepared.100
Cellular models for the screening and development of anti-hepatitis C virus agents
2009, Pharmacology and Therapeutics5,6-Dihydro-1H-pyridin-2-ones as potent inhibitors of HCV NS5B polymerase
2009, Bioorganic and Medicinal Chemistry LettersDiscovery of tricyclic 5,6-dihydro-1H-pyridin-2-ones as novel, potent, and orally bioavailable inhibitors of HCV NS5B polymerase
2009, Bioorganic and Medicinal Chemistry Letters