- Discovery of a novel aminopyrazine series as selective PI3Kα inhibitors
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We report the discovery of a novel aminopyrazine series of PI3Kα inhibitors, designed by hybridizing two known scaffolds of PI3K inhibitors. We describe the progress achieved from the first compounds plagued with poor general kinase selectivity to compounds showing high selectivity for PI3Kα over PI3Kβ and excellent general kinase selectivity. This effort culminated with the identification of compound 5 displaying high potency and selectivity, and suitable physiochemical and pharmacokinetic properties for oral administration. In vivo, compound 5 showed good inhibition of tumour growth (86% tumour growth inhibition at 50?mg/kg twice daily orally) in the MCF7 xenograft model in mice.
- Barlaam, Bernard,Cosulich, Sabina,Fitzek, Martina,Germain, Hervé,Green, Stephen,Hanson, Lyndsey L.,Harris, Craig S.,Hancox, Urs,Hudson, Kevin,Lambert-van der Brempt, Christine,Lamorlette, Maryannick,Magnien, Fran?oise,Ouvry, Gilles,Page, Ken,Ruston, Linette,Ward, Lara,Delouvrié, Bénédicte
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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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Paragraph 00500
(2018/07/05)
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- Compounds used as JAK inhibitor, and use of compounds
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The invention provides compounds used as a JAK inhibitor, and a use of the compounds, and concretely provides compounds (represented by formula (I)) with JAK inhibition activity or a stereoisomer, a geometric isomer, a tautomer, a racemate, a nitrogen oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, and a medicinal composition including the compounds. The invention also discloses a use of the compounds or the medicinal composition thereof in the preparation of medicines used for treating autoimmune diseases or proliferative diseases.
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Paragraph 0357; 0358; 0359; 0340
(2017/08/27)
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- SYK INHIBITORS
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The present disclosure relates to compounds that are Syk inhibitors and to their use in the treatment of various disease slates, including cancer and inflammatory conditions. In particular embodiments, the structure of the compounds is given by Formula I: wherein R1, R2, R3, and R4 are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk. In certain embodiments, also disclosed are methods for treating a cancer in a subject (e.g., a human) in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, in combination with a vinca-alkaloid, or a pharmaceutically acceptable salt thereof.
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Paragraph 0280
(2016/02/26)
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- TREATMENT OF CHRONIC GRAFT VERSUS HOST DISEASE WITH SYK INHIBITORS
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The present disclosure provides methods of utilizing Syk inhibiting compounds in the treatment for graft versus host disease (GVHD) in a human, including acute graft versus host disease (aGVHD) and chronic graft versus host disease (cGVHD), including the use of compounds selected from the group consisting of the formulas below: (I) and (II).
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Page/Page column 33
(2016/11/17)
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- SYK INHIBITORS
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The present disclosure relates to compounds that are Syk inhibitors and to their use in the treatment of various disease states, including cancer and inflammatory conditions. In particular embodiments, the structure of the compounds is given by Formula I: wherein R1, R2, R3, and R4 are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts or co-crystals thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk.
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Paragraph 0242; 0244
(2015/07/02)
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- SYK INHIBITORS
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The present disclosure relates to compounds that are Syk inhibitors and to their use in the treatment of various disease states, including cancer and inflammatory conditions. In particular embodiments, the structure of the compounds is given by Formula I: wherein R1, R2, R3, and R4 are as described herein. The present disclosure further provides pharmaceutical compositions that include a compound of Formula I, or pharmaceutically acceptable salts or co-crystals thereof, and methods of using these compounds and compositions to treat conditions mediated by Syk.
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Page/Page column 99
(2015/07/15)
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- Novel Heterocyclic Compounds and Uses Thereof
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New substituted heterocyclic compounds, compositions containing them, and methods of using them for the inhibition of Raf kinase activity are provided. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a Raf kinase mediated disorder, such as cancer.
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Paragraph 0391
(2013/08/28)
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- NOVEL HETEROCYCLIC COMPOUNDS AND USES THEROF
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New substituted heterocyclic compounds, compositions containing them, and methods of using them for the inhibition of Raf kinase activity are provided. The new compounds and compositions may be used either alone or in combination with at least one additional agent for the treatment of a Raf kinase mediated disorder, such as cancer.
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Page/Page column 118
(2009/10/22)
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- HETEROARYL COMPOUNDS, COMPOSITIONS THEREOF, AND METHODS OF TREATMENT THEREWITH
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Provided herein are Heteroaryl Compounds having the following structure: (I) wherein R1, R2, L, X, Y, Z, Q, A and B are as defined herein, compositions comprising an effective amount of a Heteroaryl Compound and methods for treating or preventing cancer, inflammatory conditions, immunological conditions, metabolic conditions and conditions treatable or preventable by inhibition of a kinase pathway comprising administering an effective amount of a Heteroaryl Compound to a patient in need thereof.
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Page/Page column 101
(2008/12/05)
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- CRF1 RECEPTOR LIGANDS COMPRISING FUSED BICYCLIC HETEROARYL MOIETIES
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Substituted heteroaryl fused pyridine, pyrazine, and related heterobicyclic compounds that act as selective modulators of CRF1 receptors are provided. These compounds are useful in the treatment of a number of CNS and periphereal disorders, particularly stress, anxiety, depression, cardiovascular disorders, gastrointestinal disorders, and eating disorders. Methods of treatment of such disorders as well as packaged pharmaceutical compositions are also provided. Compounds provided herein are also useful as probes for the localization of CRF receptors and as standards in assays for CRF receptor binding. Methods of using the compounds in receptor localization studies are given.
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Page/Page column 85
(2008/12/07)
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- NOVEL N-PYRAZINIL-PHENYLSULFONAMIDE DERIVATIVES AS CHEMOKINE RECEPTOR MODULATORS FOR USE IN THE TREATMENT OF ASTHMA
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The invention provides a compound of formula (I), wherein R1, R2 and R3 are as defined in the specification, pharmaceutical compositions containing them, a process for preparing the pharmaceutical compositions, and their use in therapy.
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Page/Page column 29-30
(2010/11/26)
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- Real light emitter in the bioluminescence of the calcium-activated photoproteins aequorin and obelin: light emission from the singlet-excited state of coelenteramide phenolate anion in a contact ion pair
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Fluorescence of the phenolate anion (3(O)-) and the amide anion (5(N)-) of coelenteramide analogues in ion pairs with various counter cations was systematically investigated to elucidate the ionic structure of the light emitter in th
- Mori, Kotaro,Maki, Shojiro,Niwa, Haruki,Ikeda, Hiroshi,Hirano, Takashi
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p. 6272 - 6288
(2007/10/03)
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- SULPHONAMIDE COMPOUNDS THAT MODULATE CHEMOKINE RECEPTOR ACTIVITY (CCR4)
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The invention relates to sulphonamide compounds, processes and intermediates used in their preparation, pharmaceutical compositions containing them and their use in therapy.
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- Studies on Pyrazines. 6. A Facile Separation Method for a Mixture of the Isomeric 2-Amino-3,5, and 6-methylpyrazines
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This paper describes a facile separation method for a mixture of the isomeric aminomethylpyrazines by two-stage processes.Thus the mixture of aminomethylpyrazines was converted into that of the aminobromomethylpyrazines, which could be separated by chromatography on silica gel.Each of the bromopyrazines was hydrogenated to regenerate the original aminopyrazine as a pure form.
- Sato, Nobuhiro
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p. 143 - 147
(2007/10/02)
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