- ANTI-INFLUENZA VIRUS PYRIMIDINE DERIVATIVE
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The present invention discloses a class of anti-influenza virus compounds, and the use thereof in the preparation of a drug for treating diseases associated with influenza viruses. In particular, the present invention discloses a compound represented by formula (I) and a pharmaceutically acceptable salt thereof.
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- FORMULATIONS OF AZAINDOLE COMPOUNDS
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The present invention relates to pharmaceutical compositions, each comprising a multitude of granules that make up an intragranular phase of the composition, wherein the granules are produced by fluid bed granulation and comprise a HCI salt of Compound (1
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- PYRROLO[2,3-B]PYRIDIN DERIVATIVES AS INHIBITORS OF INFLUENZA VIRUS REPLICATION
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Provided herein are compounds of Formula A, B or C that can inhibit the replication of influenza viruses, reduce the amount of influenza viruses, and/or treat influenza.
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- Synthesis of Differentially Protected Azatryptophan Analogs via Pd2(dba)3/XPhos Catalyzed Negishi Coupling of N-Ts Azaindole Halides with Zinc Derivative from Fmoc-Protected tert-Butyl (R)-2-Amino-3-iodopropanoate
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Unnatural amino acids play an important role in peptide based drug discovery. Herein, we report a class of differentially protected azatryptophan derivatives synthesized from N-tosyl-3-haloazaindoles 1 and Fmoc-protected tert-butyl iodoalanine 2 via a Neg
- Nimje, Roshan Y.,Vytla, Devaiah,Kuppusamy, Prakasam,Velayuthaperumal, Rajeswari,Jarugu, Lokesh Babu,Reddy, China Anki,Chikkananjaiah, Nanjundaswamy Kanikahalli,Rampulla, Richard A.,Cavallaro, Cullen L.,Li, Jianqing,Mathur, Arvind,Gupta, Anuradha,Roy, Amrita
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p. 11519 - 11530
(2020/10/12)
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- Novel heterocyclic compounds and medicinal application of same as anti-influenza virus inhibitors
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The invention provides heterocyclic compounds represented by a formula (I) as described in the specification or a pharmaceutically acceptable salt thereof, a preparation method thereof, and application of the heterocyclic compounds to the preparation of m
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- Heterocyclic compounds and, their compositions and their use as anti-influenza virus drugs (by machine translation)
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The invention provides a class of heterocyclic (I) compounds or pharmaceutically acceptable salts thereof as shown in formula (I) or a preparation method thereof as well A as a preparation method and application of the compounds in. preparation of drugs for treating or, preventing influenza viruses RNA. (by machine translation)
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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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- INHIBITORS OF INFLUENZA VIRUS REPLICATION, APPLICATION METHODS AND USES THEREOF
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The invention provides a novel 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 manufacture of medicaments for treating of influenza.
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- Influenza virus replication inhibitor and application thereof
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The invention provides a type of compounds serving as an influenza virus replication inhibitor, a preparation method of the compounds, a pharmaceutical composition comprising the compounds, and application of the compounds and the pharmaceutical composition thereof in treatment of influenza.
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- PYRROLOPYRIMIDINE DERIVATIVES USEFUL AS INHIBITORS OF INFLUENZA VIRUS REPLICATION
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Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient a safe and effective amount of a compound represented by any of Formulas l-lll, or a pharmaceutically acceptable salt thereof. A pharmaceutical composition comprises a safe and effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.
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- INHIBITORS OF INFLUENZA VIRUS REPLICATION, APPLICATION METHODS AND USES THEREOF
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The invention provides a novel 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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- Discovery of Novel, Orally Bioavailable β-Amino Acid Azaindole Inhibitors of Influenza PB2
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In our efforts to develop novel small-molecule inhibitors for the treatment of influenza, we utilized molecular modeling and the X-ray crystal structure of the PB2 subunit of the influenza polymerase to optimize a series of acyclic β-amino acid inhibitors, highlighted by compound 4. Compound 4 showed good oral exposure in both rat and mouse. More importantly, it showed strong potency versus multiple influenza-A strains, including pandemic 2009 H1N1 and avian H5N1 strains and showed a strong efficacy profile in a mouse influenza model even when treatment was initiated 48 h after infection. Compound 4 offers good oral bioavailability with great potential for the treatment of both pandemic and seasonal influenza.
- Farmer, Luc J.,Clark, Michael P.,Boyd, Michael J.,Perola, Emanuele,Jones, Steven M.,Tsai, Alice,Jacobs, Marc D.,Bandarage, Upul K.,Ledeboer, Mark W.,Wang, Tiansheng,Deng, Hongbo,Ledford, Brian,Gu, Wenxin,Duffy, John P.,Bethiel, Randy S.,Shannon, Dean,Byrn, Randal A.,Leeman, Joshua R.,Rijnbrand, Rene,Bennett, Hamilton B.,O’Brien, Colleen,Memmott, Christine,Nti-Addae, Kwame,Bennani, Youssef L.,Charifson, Paul S.
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supporting information
p. 256 - 260
(2017/03/08)
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- METHODS OF PREPARING INHIBITORS OF INFLUENZA VIRUSES REPLICATION
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A method of preparing a compound of Formula (I) or a pharmaceutically acceptable salt thereof comprises: (a) reacting Compound (1) or (b) a pharmaceutically acceptable salt thereof with Compound (2) in the presence of water, an organic solvent, a base, an
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- Discovery of VX-509 (Decernotinib): A Potent and Selective Janus Kinase 3 Inhibitor for the Treatment of Autoimmune Diseases
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While several therapeutic options exist, the need for more effective, safe, and convenient treatment for a variety of autoimmune diseases persists. Targeting the Janus tyrosine kinases (JAKs), which play essential roles in cell signaling responses and can contribute to aberrant immune function associated with disease, has emerged as a novel and attractive approach for the development of new autoimmune disease therapies. We screened our compound library against JAK3, a key signaling kinase in immune cells, and identified multiple scaffolds showing good inhibitory activity for this kinase. A particular scaffold of interest, the 1H-pyrrolo[2,3-b]pyridine series (7-azaindoles), was selected for further optimization in part on the basis of binding affinity (Ki) as well as on the basis of cellular potency. Optimization of this chemical series led to the identification of VX-509 (decernotinib), a novel, potent, and selective JAK3 inhibitor, which demonstrates good efficacy in vivo in the rat host versus graft model (HvG). On the basis of these findings, it appears that VX-509 offers potential for the treatment of a variety of autoimmune diseases.
- Farmer, Luc J.,Ledeboer, Mark W.,Hoock, Thomas,Arnost, Michael J.,Bethiel, Randy S.,Bennani, Youssef L.,Black, James J.,Brummel, Christopher L.,Chakilam, Ananthsrinivas,Dorsch, Warren A.,Fan, Bin,Cochran, John E.,Halas, Summer,Harrington, Edmund M.,Hogan, James K.,Howe, David,Huang, Hui,Jacobs, Dylan H.,Laitinen, Leena M.,Liao, Shengkai,Mahajan, Sudipta,Marone, Valerie,Martinez-Botella, Gabriel,McCarthy, Pamela,Messersmith, David,Namchuk, Mark,Oh, Luke,Penney, Marina S.,Pierce, Albert C.,Raybuck, Scott A.,Rugg, Arthur,Salituro, Francesco G.,Saxena, Kumkum,Shannon, Dean,Shlyakter, Dina,Swenson, Lora,Tian, Shi-Kai,Town, Christopher,Wang, Jian,Wang, Tiansheng,Wannamaker, M. Woods,Winquist, Raymond J.,Zuccola, Harmon J.
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p. 7195 - 7216
(2015/10/05)
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- METHODS OF PREPARING INHIBITORS OF INFLUENZA VIRUSES REPLICATION
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A method of preparing Compound (1) or a pharmaceutically acceptable salt thereof: comprises: (a) reacting Compound (X): a pharmaceutically acceptable salt thereof with Compound (Y): in the presence of a palladium catalyst and a carbonate or phosphate base
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- INHIBITORS OF INFLUENZA VIRUSES REPLICATION
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Polymorphic forms of Compound (1) or a pharmaceutically acceptable salt thereof, wherein Compound (1) is represented by the following structural formula: are Form A of HCl salt of Compound (1)·1/2Η20, Form F of HCl salt of Compound (1)·3Η2
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- Discovery of a novel, first-in-class, orally bioavailable azaindole inhibitor (VX-787) of influenza PB2
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In our effort to develop agents for the treatment of influenza, a phenotypic screening approach utilizing a cell protection assay identified a series of azaindole based inhibitors of the cap-snatching function of the PB2 subunit of the influenza A viral polymerase complex. Using a bDNA viral replication assay (Wagaman, P. C., Leong, M. A., and Simmen, K. A. Development of a novel influenza A antiviral assay. J. Virol. Methods 2002, 105, 105-114) in cells as a direct measure of antiviral activity, we discovered a set of cyclohexyl carboxylic acid analogues, highlighted by VX-787 (2). Compound 2 shows strong potency versus multiple influenza A strains, including pandemic 2009 H1N1 and avian H5N1 flu strains, and shows an efficacy profile in a mouse influenza model even when treatment was administered 48 h after infection. Compound 2 represents a first-in-class, orally bioavailable, novel compound that offers potential for the treatment of both pandemic and seasonal influenza and has a distinct advantage over the current standard of care treatments including potency, efficacy, and extended treatment window.
- Clark, Michael P.,Ledeboer, Mark W.,Davies, Ioana,Byrn, Randal A.,Jones, Steven M.,Perola, Emanuele,Tsai, Alice,Jacobs, Marc,Nti-Addae, Kwame,Bandarage, Upul K.,Boyd, Michael J.,Bethiel, Randy S.,Court, John J.,Deng, Hongbo,Duffy, John P.,Dorsch, Warren A.,Farmer, Luc J.,Gao, Huai,Gu, Wenxin,Jackson, Katrina,Jacobs, Dylan H.,Kennedy, Joseph M.,Ledford, Brian,Liang, Jianglin,Maltais, Fran?ois,Murcko, Mark,Wang, Tiansheng,Wannamaker, M. Woods,Bennett, Hamilton B.,Leeman, Joshua R.,McNeil, Colleen,Taylor, William P.,Memmott, Christine,Jiang, Min,Rijnbrand, Rene,Bral, Christopher,Germann, Ursula,Nezami, Azin,Zhang, Yuegang,Salituro, Francesco G.,Bennani, Youssef L.,Charifson, Paul S.
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p. 6668 - 6678
(2014/10/15)
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- INHIBITORS OF INFLUENZA VIRUSES REPLICATION
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Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient an effective amount of a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (I) are as described herein. A compound is represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (I) are as described herein. A pharmaceutical composition comprises an effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.
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Page/Page column 65
(2013/03/26)
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