- Target-Based Identification and Optimization of 5-Indazol-5-yl Pyridones as Toll-like Receptor 7 and 8 Antagonists Using a Biochemical TLR8 Antagonist Competition Assay
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Inappropriate activation of endosomal TLR7 and TLR8 occurs in several autoimmune diseases, in particular systemic lupus erythematosus (SLE). Herein, the development of a TLR8 antagonist competition assay and its application for hit generation of dual TLR7
- Knoepfel, Thomas,Nimsgern, Pierre,Jacquier, Sébastien,Bourrel, Marjorie,Vangrevelinghe, Eric,Glatthar, Ralf,Behnke, Dirk,Alper, Phil B.,Michellys, Pierre-Yves,Deane, Jonathan,Junt, Tobias,Zipfel, Géraldine,Limonta, Sarah,Hawtin, Stuart,Andre, Cedric,Boulay, Thomas,Loetscher, Pius,Faller, Michael,Blank, Jutta,Feifel, Roland,Betschart, Claudia
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p. 8276 - 8295
(2020/08/24)
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- ARYL, HETEROARY, AND HETEROCYCLIC PHARMACEUTICAL COMPOUNDS FOR TREATMENT OF MEDICAL DISORDERS
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Complement Factor D inhibitors, pharmaceutical compositions, and uses thereof, as well as processes for their manufacture are provided. The compounds provided include Formula I, Formula II, Formula III, Formula IV, and Formula V, or a pharmaceutically acceptable salt, prodrug, isotopic analog, N-oxide, or isolated isomer thereof, optionally in a pharmaceutically acceptable composition. The inhibitors described herein target Factor D and inhibit or regulate the complement cascade.
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- PARAZOLE CONDENSED-RING DERIVATIVES AND PREPARATION METHOD THEREOF AND APPLICATION THEREOF IN TREATMENT OF CANCERS, INFLAMMATION AND IMMUNE DISEASES
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The present invention relates to pyrazole fused-ring derivatives, their preparation methods, and use thereof in medicine. In particular, the present invention relates to a novel derivative represented by formula (I), and a pharmaceutically acceptable salt
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- 2,4-Diaminopyrimidine MK2 inhibitors. Part II: Structure-based inhibitor optimization
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We describe structure-based optimization of a series of novel 2,4-diaminopyrimidine MK2 inhibitors. Co-crystal structures (see accompanying Letter) demonstrated a unique inhibitor binding mode. Resulting inhibitors had IC50 values as low as 19 nM and moderate selectivity against a kinase panel. Compounds 15, 31a, and 31b inhibit TNFα production in peripheral human monocytes.
- Harris, Christopher M.,Ericsson, Anna M.,Argiriadi, Maria A.,Barberis, Claude,Borhani, David W.,Burchat, Andrew,Calderwood, David J.,Cunha, George A.,Dixon, Richard W.,Frank, Kristine E.,Johnson, Eric F.,Kamens, Joanne,Kwak, Silvia,Li, Biqin,Mullen, Kelly D.,Perron, Denise C.,Wang, Lu,Wishart, Neil,Wu, Xiaoyun,Zhang, Xiaolei,Zmetra, Tami R.,Talanian, Robert V.
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scheme or table
p. 334 - 337
(2010/04/02)
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