Enantioselective synthesis of Janus kinase inhibitor INCB018424 via an organocatalytic aza-Michael reaction
Abstract
An enantioselective synthesis of INCB018424 via organocatalytic asymmetric aza-Michael addition of pyrazoles (16 or 20) to (E)-3-cyclopentylacrylaldehyde (23) using diarylprolinol silyl ether as the catalyst was developed. Michael adducts (R)-24 and (R)-27 were isolated in good yield and high ee and were readily converted to INCB018424.
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Ruxolitinib negatively influences JAK1-dependent reactions, specifically the generation of pJAK1_gp130 and pJAK1_pgp130.
“The JAK inhibitor Ruxolitinib (Lin et al., 2009; Quintas-Cardama et al., 2010) negatively influences JAK1-dependent reactions in the model, specifically the generation of pJAK1_gp130 and pJAK1_pgp130.”
From Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib (2017) · cites this paper as Lin et al., 2009
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- Authors
- Lin, Q., Meloni, D., Pan, Y., Xia, M., Rodgers, J., Shepard, S., Li, M., Galya, L., Metcalf, B., Yue, T.-Y., Liu, P., & Zhou, J.
- Affiliations
- Incyte (United States) (US)
- Corresponding author
- Lin, Qiyan
- Venue
- Organic Letters
- Publisher
- American Chemical Society (ACS)
- Published
- 2009-03-27
- Volume
- 11
- Issue
- 9
- Pages
- 1999-2002
- ISSN
- 1523-7052 (ISSN-L)
- 1523-7060
- OpenAlex
- W2052731400
- Cited by
- 171
- References
- 25
- Citations by year
- 2026: 10 · 2025: 4 · 2024: 10 · 2023: 12 · 2022: 10 · 2021: 6 · 2020: 5 · 2019: 2 · 2018: 7 · 2017: 6 · 2016: 12 · 2015: 15 · 2014: 10 · 2013: 14 · 2012: 13
- FWCI
- 7.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Organic Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Asymmetric Synthesis and Catalysis
- Physical Sciences › Chemistry › Inorganic Chemistry › Asymmetric Hydrogenation and Catalysis
- Physical Sciences › Chemistry › Organic Chemistry › Axial and Atropisomeric Chirality Synthesis
- Keywords
- JAK inhibitors, asymmetric synthesis, organocatalysis, pyrazole derivatives, chiral amines
- MeSH terms
- Benzoates, Catalysis, Nitriles, Pyrazoles, Pyrimidines, Stereoisomerism, Molecular Structure, Protein Kinase Inhibitors, Janus Kinases
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