- IRAK4 kinase inhibitor and preparation method thereof
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The present invention provides a compound represented by a general formula I, and a pharmaceutically acceptable salt, a stereoisomer, an ester, a prodrug, a solvate and a deuterated compound thereof,and the compound is an IRAK4 kinase inhibitor, and can be used for prevention and/or treatment of IRAK4 related diseases, such as autoimmune diseases, inflammatory diseases, cancers, heteroimmune diseases, thromboembolism, atherosclerosis, myocardial infarction and metabolic syndrome.
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- Development of a Scalable Enantioselective Synthesis of JAK Inhibitor Upadacitinib
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Process development of a six-stage synthesis of upadacitinib, a JAK1 inhibitor, is described. It is highlighted by an enantioselective and diastereoselective hydrogenation of a tetrasubstituted olefin to set the two pyrrolidine stereocenters. Preparation of the main fragments and strategies to link them together, optimization of the imidazole cyclization, and in-depth understanding of the formation of the urea moiety at the final stage are discussed.
- Bhagavatula, Lakshmi,Christesen, Alan,Dunn, Travis B.,Ickes, Andrew,Kotecki, Brian J.,Marek, James C.,Morrill, Westin H.,Moschetta, Eric,Mulhern, Mathew,Rasmussen, Michael,Reynolds, Troy,Rozema, Michael J.,Yu, Su
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- Preparation of (5 - tosyl - 555H-pyrrolo [2, 3 - b] pyrazine -2 -yl) carbamic acid tert-butyl ester (by machine translation)
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The present invention relates to (5 - tosyl - 555H-pyrrolo [2. The preparation method comprises the following steps: 3 - b,2 - diamine as a starting raw material, synthesizing (-2, 5 -] pyrazino 5 -yl) carbamic acid tert-butyl ester through a series of re
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- Synthesis method of JAK (Janus Kinase) inhibitor
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The invention discloses a synthesis method of a JAK (Janus Kinase) inhibitor. The synthesis method comprises the following steps: carrying out condensation on an intermediate A-8 and an intermediate B-3 to obtain an intermediate AB-1; carrying out deprotection on the intermediate AB-1 to obtain an intermediate AB-2; carrying out cyclization on the AB-2 to obtain an intermediate AB-3; carrying outthe deprotection on the intermediate AB-3 to obtain an intermediate AB-4; carrying out the deprotection on the AB-4 again to obtain an intermediate AB-5; carrying out condensation reaction on the AB-5to obtain the JAK inhibitor 1. The synthesis method disclosed by the invention has the main advantages that the intermediate A-8 is prepared through a chiral catalysis method in a high-yield and high-chiral-purity manner, and the intermediate B-3 and the JAK inhibitor 1 are prepared in a high-yield manner. Useless enantiomers are nearly not generated so that the pressure on the environment is reduced; meanwhile, the reaction yield is high, the operation is simple and the post-treatment is simple and convenient. According to the synthesis method, reaction conditions also can be applied to large-batch preparation and are suitable for industrial production, so that the synthesis method has relatively high practical value and social and economic benefits.
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- Influenza virus replication inhibitors and uses thereof (by machine translation)
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The invention provides a compound as an influenza virus replication inhibitor, a method for preparing the same, a pharmaceutical composition containing the compound and application. (by machine translation)
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- Upadacitinib tartrate: Tyrosine-protein kinase JAK1 inhibitor Treatment of autoimmune inflammatory diseases Treatment of rheumatoid arthritis
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Upadacitinib tartrate (ABT-494) is a potent and selective tyrosine-protein kinase JAK1 inhibitor being developed for the treatment of systemic autoimmune inflammatory diseases, including rheumatoid arthritis (RA), Crohn's disease, ulcerative colitis and psoriatic arthritis. In vitro, upadacitinib demonstrated higher selectivity for inhibiting JAK1 over JAK2 and JAK3, suggesting a potentially improved therapeutic profile in treating patients with inflammatory diseases compared to nonselective JAK inhibitors. Upadacitinib has demonstrated safety and efficacy in phase II trials in patients with RA and inflammatory bowel disease, and is currently in phase III development for these indications.
- Gajdosik
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p. 731 - 743
(2018/11/21)
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- INHIBITORS OF INFLUENZA VIRUS REPLICATION AND USES THEREOF
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The invention provides a class of compounds as inhibitors of influenza virus replication, preparation methods thereof, pharmaceutical compositions containing these compounds, and uses of these compounds and pharmaceutical compositions thereof in the treatment of influenza.
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- JAK1 SELECTIVE INHIBITOR AND USES THEREOF
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The invention relates to the use of a JAK1 kinase-selective inhibitor that has minimal inhibitory activity towards Jak2 kinase for treating a disease, such as an inflammatory disease (e.g., moderate to severe Rheumatoid Arthritis) and/or bone loss, either
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Paragraph 0187
(2015/05/05)
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- Design and synthesis of tricyclic cores for kinase inhibition
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Interest in therapeutic kinase inhibitors continues to grow beyond success in oncology. To date, ATP-mimetic kinase inhibitors have focused primarily on monocyclic and bicyclic heterocyclic cores. We sought to expand on the repertoire of potential cores for kinase inhibition by exploring tricyclic variants of classical bicyclic hinge binding motifs such as pyrrolopyridine and pyrrolopyrazine. Herein we describe the syntheses of eight alternative tricyclic cores as well as in vitro screening results for representative kinases of potential therapeutic interest.
- Van Epps, Stacy,Fiamengo, Bryan,Edmunds, Jeremy,Ericsson, Anna,Frank, Kristine,Friedman, Michael,George, Dawn,George, Jonathan,Goedken, Eric,Kotecki, Brian,Martinez, Gloria,Merta, Philip,Morytko, Michael,Shekhar, Shashank,Skinner, Barbara,Stewart, Kent,Voss, Jeffrey,Wallace, Grier,Wang, Lu,Wishart, Neil
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p. 693 - 698
(2013/03/13)
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