Discovery of Narlaprevir (SCH 900518): A Potent, Second Generation HCV NS3 Serine Protease Inhibitor
Open accessAbstract
Boceprevir (SCH 503034), 1, a novel HCV NS3 serine protease inhibitor discovered in our laboratories, is currently undergoing phase III clinical trials. Detailed investigations toward a second generation protease inhibitor culminated in the discovery of narlaprevir (SCH 900518), 37, with improved potency (∼10-fold over 1), pharmacokinetic profile and physicochemical characteristics, currently in phase II human trials. Exploration of synthetic sequence for preparation of 37 resulted in a route that required no silica gel purification for the entire synthesis.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Boceprevir, telaprevir, and narlaprevir use a ketoamide electrophile to covalently engage the catalytic serine of NS3/4a.
“These compounds, along with narlaprevir113, use a ketoamide electrophile to covalently engage the catalytic serine of NS3/4a.”
From Advances in covalent drug discovery (2022) · cites this paper as [113]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Replication of Subgenomic Hepatitis C Virus RNAs in a Hepatoma Cell Line
Lohmann, V., Körner, F., Koch, J. O., Herian, U., Lorenz Theilmann, I., & Bartenschlager, R. F. W. (1999) · Science · doi:10.1126/science.285.5424.110 · Cited by 2,813 · see citing works
The global burden of hepatitis C
Lavanchy, D. (2009) · Liver International · doi:10.1111/j.1478-3231.2008.01934.x · Cited by 1,353 · see citing works
Mechanism of action of interferon and ribavirin in treatment of hepatitis C
Feld, J. J., & Hoofnagle, J. H. (2005) · Nature · doi:10.1038/nature04082 · Cited by 996 · see citing works
An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus
Lamarre, D., Anderson, P. C., Bailey, M. D., Beaulieu, P. L., Bolger, G. T., Bonneau, P. R., Bös, M., Cameron, D. R., Cartier, M., Cordingley, M. G., et al. (2003) · Nature · doi:10.1038/nature02099 · Cited by 918 · see citing works
Replication of hepatitis C virus
Bartenschlager, R. F. W., & Lohmann, V. (2000) · Microbiology · doi:10.1099/0022-1317-81-7-1631 · Cited by 612 · see citing works
Kolykhalov, A. A., Mihalik, K., Feinstone, S. M., & Rice, C. M. (2000) · Journal of Virology · doi:10.1128/jvi.74.4.2046-2051.2000 · Cited by 606 · see citing works
Reesink, H. W., Zeuzem, S., Weegink, C. J., et al. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.07.013 · Cited by 401 · see citing works
Perni, R. B., Almquist, S. J., Byrn, R. A., Chandorkar, G., Chaturvedi, P. R., Courtney, L. F., Decker, C. J., Dinehart, K., Gates, C. A., Harbeson, S. L., et al. (2006) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.50.3.899-909.2006 · Cited by 391 · see citing works
The Scientific Challenge of Hepatitis C
Cohen, J. (1999) · Science · doi:10.1126/science.285.5424.26 · Cited by 352 · see citing works
Venkatraman, S., Bogen, S. L., Arasappan, A., et al. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm060325b · Cited by 281 · see citing works
Self-citationPreclinical Characteristics of the Hepatitis C Virus NS3/4A Protease Inhibitor ITMN-191 (R7227)
Seiwert, S. D., Andrews, S. W., Jiang, Y., Serebryany, V., Tan, H. T., Kossen, K., Rajagopalan, P. T. R., Misialek, S., Stevens, S., Stoycheva, A. D., et al. (2008) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00699-08 · Cited by 176 · see citing works
Raboisson, P., de Kock, H., Rosenquist, Å., Nilsson, M., Oden, L. S., Lin, T., Roue, N., Ivanov, V., Wähling, H., Wickström, K., et al. (2008) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2008.07.088 · Cited by 145 · see citing works
MK-7009, a Potent and Selective Inhibitor of Hepatitis C Virus NS3/4A Protease
Liverton, N. J., Carroll, S. S., DiMuzio, J. M., Fandozzi, C. M., Graham, D. J., Hazuda, D. J., Holloway, M. K., Ludmerer, S. W., McCauley, J. A., McIntyre, C. J., et al. (2009) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00677-09 · Cited by 141 · see citing works
A Continuous Spectrophotometric Assay for the Hepatitis C Virus Serine Protease
Zhang, R., Beyer, B. M., Durkin, J., et al. (1999) · Analytical Biochemistry · doi:10.1006/abio.1999.4109 · Cited by 92 · see citing works
Emerging therapies for hepatitis C virus infection
Dymock, B. W. (2001) · Emerging Drugs · doi:10.1517/14728214.6.1.13 · Cited by 64 · see citing works
A review of HCV protease inhibitors.
Chen, K. X., & Njoroge, F. G. (2009) · PubMed · Cited by 56 · see citing works
Self-citationTong, X., Arasappan, A., Bennett, F., et al. (2010) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.00135-10 · Cited by 45 · see citing works
Self-citationBogen, S. L., Pan, W., Ruan, S., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm801632a · Cited by 26 · see citing works
Self-citationReesink, H. W., Bergmann, J., de Bruijne, J., et al. (2009) · Journal of Hepatology · doi:10.1016/s0168-8278(09)60088-x · Cited by 25 · see citing works
Arasappan, A., Padilla, A. I., Jao, E., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm801616e · Cited by 19 · see citing works
Self-citationVenkatraman, S., Blackman, M., Wu, W., et al. (2009) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2009.05.012 · Cited by 13 · see citing works
Self-citationTong, X., Arasappan, A., Bennett, F., et al. (2009) · Journal of Hepatology · doi:10.1016/s0168-8278(09)60969-7 · Cited by 1 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- Meanwell N. A.; Kadow J. F.; Scola P. M. Progress toward the discovery and development of specifically targeted inhibitors of hepatitis C virus. Annu. Rep. Med. Chem. 2009, 44397–440. [Google Scholar]
- Zeuzem S.; Sarrazin C.; Rouzier R.; Tarral A.; Brion N.; Forestier N.; Gupta S.; Deckman D.; Fellows K.; Hussain M.; Cutler D.; Zhang J. In 56th Annual Meeting of AASLD, San Francisco, CA, 2005. [Google Scholar]
Cited by
Sorted by citations
Oral Druggable Space beyond the Rule of 5: Insights from Drugs and Clinical Candidates
Doak, B. C., Over, B., Giordanetto, F., & Kihlberg, J. (2014) · Chemistry & Biology · doi:10.1016/j.chembiol.2014.08.013 · Cited by 835 · see citing works
Advances in covalent drug discovery
Boike, L., Henning, N. J., & Nomura, D. K. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00542-z · Cited by 823 · see citing works
Hepatitis C virus NS3/4a protease inhibitors
McCauley, J. A., & Rudd, M. T. (2016) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2016.07.015 · Cited by 120 · see citing works
- Authors
- Arasappan, A., Bennett, F., Bogen, S. L., Venkatraman, S., Blackman, M., Chen, K. X., Hendrata, S., Huang, Y., Huelgas, R. M., Nair, L., Padilla, A. I., Pan, W., Pike, R., Pinto, P., Ruan, S., Sannigrahi, M., Velazquez, F., Vibulbhan, B., Wu, W., Yang, W., Saksena, A. K., Girijavallabhan, V., Shih, N.-Y., Kong, J., Meng, T., Jin, Y., Wong, J., McNamara, P., Prongay, A., Madison, V., Piwinski, J. J., Cheng, K.-C., Morrison, R., Malcolm, B., Tong, X., Ralston, R., & Njoroge, F. G.
- Affiliations
- Schering Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033
- Corresponding author
- Arasappan, Ashok
- Bennett, Frank
- Venue
- ACS Medicinal Chemistry Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2010-02-15
- Volume
- 1
- Issue
- 2
- Pages
- 64-69
- ISSN
- 1948-5875 (ISSN-L)
- PMC
- PMC4007962
- OpenAlex
- W2023033918
- Cited by
- 102
- References
- 22
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 9 · 2023: 12 · 2022: 5 · 2021: 6 · 2020: 6 · 2019: 5 · 2018: 3 · 2017: 6 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 5 · 2012: 7
- FWCI
- 3.99
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- ACS Medicinal Chemistry Letters (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hepatology › Hepatitis C virus research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
- Keywords
- boceprevir, hepatitis C virus, synthetic route, pharmacokinetics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
