- INHIBITORS OF HEPATITIS C VIRUS REPLICATION
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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.
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Paragraph 0630-0631
(2019/05/15)
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- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
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The present invention provides compounds of formula I: or a pharmaceutically acceptable salt, tautomer, or stereoisomer, thereof, wherein the variables are as defined herein. The present invention further provides pharmaceutical compositions comprising su
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Paragraph 0416
(2014/09/30)
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- Discovery of a series of 2,5-diaminopyrimidine covalent irreversible inhibitors of Bruton's tyrosine kinase with in vivo antitumor activity
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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.
- Li, Xitao,Zuo, Yingying,Tang, Guanghui,Wang, Yan,Zhou, Yiqing,Wang, Xueying,Guo, Tianlin,Xia, Mengying,Ding, Ning,Pan, Zhengying
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p. 5112 - 5128
(2014/07/08)
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- INHIBITORS OF HEPATITIS C VIRUS REPLICATION
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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.
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Page/Page column 90
(2010/11/04)
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- 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
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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
- 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
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p. 1681 - 1694
(2008/12/20)
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- Therapeutic quinazoline derivatives
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A compound of formula (I) or a salt, ester, amide or prodrug thereof; where X is O, or S, S(O), S(O)2 or NR6 where R6 is hydrogen of C1-6alkyl; R5 is an optionally substituted 6-membered aromatic ring containing at least one nitrogen atom, and R1, R2, R3, R4 are independently selected from halogeno, cyano, nitro, C1-3alkylsulphanyl, —N(OH)R7— (wherein R7 is hydrogen, or C1-3alkyl), or R9X1— (wherein X1 represents a direct bond, —O—, —CH2—, —OC(O), —C(O)—, —S—, —SO—, —SO2—, —NR10C(O)—, —C(O)NR11—, —SO2NR12—, —NR13SO2— or NR14— (wherein R10, R11, R12, R13 and R14 each independently represents hydrogen, C1-3alkyl or C1-3alkoxyC2-3alkyl), and R9 is hydrogen, optionally substituted hydrocarbyl, optionally substituted heterocyclyl or optionally substituted alkoxy; provided that at least one of R2 or R3 is other than hydrogen. These compounds inhibit aurora 2 kinase and are useful in the preparation of medicaments for the treatment of proliferative disease such as cancer.
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