22715-27-1Relevant articles and documents
INHIBITORS OF HEPATITIS C VIRUS REPLICATION
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Paragraph 0630-0631, (2019/05/15)
The present invention relates to compounds of formula (I) that are useful as hepatitis C virus (HCV) NS5A inhibitors, the synthesis of such compounds, and the use of such compounds for inhibiting HCV NS5A activity, for treating or preventing HCV infections and for inhibiting HCV viral replication and/or viral production in a cell-based system.
Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity
Li, Xitao,Zuo, Yingying,Tang, Guanghui,Wang, Yan,Zhou, Yiqing,Wang, Xueying,Guo, Tianlin,Xia, Mengying,Ding, Ning,Pan, Zhengying
, p. 5112 - 5128 (2014/07/08)
Bruton's tyrosine kinase (Btk) is an attractive drug target for treating several B-cell lineage cancers. Ibrutinib is a first-in-class covalent irreversible Btk inhibitor and has demonstrated impressive effects in multiple clinical trials. Herein, we present a series of novel 2,5-diaminopyrimidine covalent irreversible inhibitors of Btk. Compared with ibrutinib, these inhibitors exhibited a different selectivity profile for the analyzed kinases as well as a dual-action mode of inhibition of both Btk activation and catalytic activity, which counteracts a negative regulation loop for Btk. Two compounds from this series, 31 and 38, showed potent antiproliferative activities toward multiple B-cell lymphoma cell lines, including germinal center B-cell-like diffuse large B cell lymphoma (GCB-DLBCL) cells. In addition, compound 31 significantly prevented tumor growth in a mouse xenograft model.
Structure-guided design of aminopyrimidine amides as potent, selective inhibitors of lymphocyte specific kinase: Synthesis, structure-activity relationships, and inhibition of in vivo T cell activation
DiMauro, Erin F.,Newcomb, John,Nunes, Joseph J.,Bemis, Jean E.,Boucher, Christina,Chai, Lilly,Chaffee, Stuart C.,Deak, Holly L.,Epstein, Linda F.,Faust, Ted,Gallant, Paul,Gore, Anu,Gu, Yan,Henkle, Brad,Hsieh, Faye,Huang, Xin,Kim, Joseph L.,Lee, Josie H.,Martin, Matthew W.,McGowan, David C.,Metz, Daniela,Mohn, Deanna,Morgenstern, Kurt A.,Oliveira-Dos-Santos, Antonio,Patel, Vinod F.,Powers, David,Rose, Paul E.,Schneider, Stephen,Tomlinson, Susan A.,Tudor, Yan-Yan,Turci, Susan M.,Welcher, Andrew,Zhao, Huilin,Zhu, Li,Zhu, Xiaotian
, p. 1681 - 1694 (2008/12/20)
The lymphocyte-specific kinase (Lck), a member of the Src family of cytoplasmic tyrosine kinases, is expressed in T cells and natural killer (NK) cells. Genetic evidence, including knockout mice and human mutations, demonstrates that Lck kinase activity i