- COMPOUNDS AND USES THEREOF
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The present disclosure features compounds useful for the treatment of BAF complex-related disorders.
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Page/Page column 71; 92
(2021/08/06)
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- SUBSTITUTED 1,5-NAPHTHYRIDINES OR QUINOLINES AS ALK5 INHIBITORS
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The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.
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Paragraph 226; 254; 266
(2021/05/29)
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- ALK5 INHIBITORS
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The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.
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Paragraph 0479; 0644; 0645
(2020/07/07)
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- Synthetic method of 7-bromo-1,5-naphthyridine-3-methanoic acid
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The invention provides a synthetic method of 7-bromo-1,5-naphthyridine-3-methanoic acid. The synthetic method of the 2-bromo-1,5-naphthyridine-3-methanoic acid comprises the steps of taking 1,5-naphthyridine as a raw material and reacting to generate 7-bromo-1,5-naphthyridine-3-methyl pyrazinecarboxylate; and finally hydrolyzing the 7-bromo-1,5-naphthyridine-3-methyl pyrazinecarboxylate under thealkaline condition to generate the 7-bromo-1,5-naphthyridine-3-methanoic acid. According to the synthetic method of the 7-bromo-1,5-naphthyridine-3-methanoic acid, a synthetic route which takes 1,5-naphthyridine as a raw material is provided. The synthetic method of the 7-bromo-1,5-naphthyridine-3-methanoic acid has the advantages that the synthetic route is simple, the raw materials are low in cost, are simple and are easily obtained, aftertreatment is facilitated, the success rate is high, the synthetic route is easy to enlarge and the like.
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Paragraph 0057; 0058; 0059
(2018/11/03)
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- GLYCOSIDASE INHIBITORS
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Compounds of formula (I) wherein A, R, W, Q, n and m have the meaning according to the claims can be employed, inter alia, for the treatment of tauopathies and Alzheimer's disease.
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Page/Page column 105
(2017/09/15)
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- Combination of mTOR inhibitors and P13-kinase inhibitors, and uses thereof
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The present invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth.
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Page/Page column 335; 336
(2016/04/26)
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- Design and synthesis of novel substituted naphthyridines as potential c-Met kinase inhibitors based on MK-2461
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Abstract Two series of novel 1,5-naphthyridine and 1,6-naphthyridine derivatives were designed and synthesized based on the c-Met kinase inhibitor MK-2461 under the guidance of scaffold hopping strategy. All were tested on c-Met kinase and in vitro anti-tumor activities against Hela and A549 cell lines. The results indicated that 1,6-naphthyridine was a more promising c-Met inhibitory structure core compared with 1,5-naphthyridine. Among them, 26b and 26c showed the best enzymic and cytotoxic activities. The western blot experiments implied that the cytotoxic activity of 26c might be partially through suppressing the phosphorylation of c-Met kinase.
- Wu, Jing-Fang,Liu, Ming-Ming,Huang, Shao-Xu,Wang, Yang
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p. 3251 - 3255
(2015/07/08)
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- COMBINATION OF KINASE INHIBITORS AND USES THEREOF
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The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or a receptor tyrosine kinase (RTK) in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase α and/or an RTK in a subject. In yet another aspect, a method of inhibiting phosphorylation of Akt (S473) in a cell is set forth.
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Page/Page column 63
(2015/02/19)
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- N-(1-HYDROXY-3-(PYRROLIDINYL)PROPAN-2-YL)PYRROLIDINE-3-CARBOXAMIDE DERIVATIVES AS GLUCOSYLCERAMIDE SYNTHASE INHIBITORS
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Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and compounds I for use to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).
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Paragraph 000712
(2015/05/19)
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- Discovery of 7-aryl-substituted (1,5-naphthyridin-4-yl)ureas as Aurora kinase inhibitors
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As part of our research projects to identify new chemical entities of biological interest, we developed a synthetic approach and the biological evaluation of (7-aryl-1,5-naphthyridin-4-yl)ureas as a novel class of Aurora kinase inhibitors for the treatment of malignant diseases based on pathological cell proliferation. 1,5-Naphthyridine derivatives showed excellent inhibitory activities toward Aurora kinases A and B, and the most active compound, 1-cyclopropyl-3-[7-(1-methyl-1H-pyrazol-4-yl)-1,5-naphthyridin-4-yl]urea (49), displayed IC50 values of 13 and 107 nM against Aurora kinases A and B, respectively. In addition, the selectivity toward a panel of seven cancer-related protein kinases was highlighted. In vitro ADME properties were also determined in order to rationalize the difficulties in correlating antiproliferative activity with Aurora kinase inhibition. Finally, the good safety profile of these compounds imparts promising potential for their further development as anticancer agents. Promising Aurora inhibitors: Herein we report a series of (7-aryl-1,5-naphthyridin-4-yl)ureas as a novel class of nanomolar-range Aurora kinase inhibitors. The described derivatives have good cell-penetration parameters and safety profiles, but their efficiency toward signaling pathways are insufficient to induce cell death. We also highlight their selectivity toward a panel of seven cancer-related protein kinases. Copyright
- Defaux, Julien,Antoine, Maud,Le Borgne, Marc,Schuster, Tilmann,Seipelt, Irene,Aicher, Babette,Teifel, Michael,Guenther, Eckhard,Gerlach, Matthias,Marchand, Pascal
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p. 217 - 232
(2014/01/17)
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- COMBINATION OF KINASE INHIBITORS AND USES THEREOF
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The present invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In another aspect, the invention provides for a method for treating a disease condition associated with PI3-kinase a and/or mTOR in a subject. In yet another aspect, a method of inhibiting phosphorylation of both Akt (S473) and Akt (T308) in a cell is set forth. The present invention also provides a pharmaceutical kit effective for treating a disease condition associated with PI3 -kinase α and/or mTOR in a subject.
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Paragraph 00641
(2014/10/04)
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- Discovery of (7-aryl-1,5-naphthyridin-2-yl)ureas as dual inhibitors of ERK2 and Aurora B kinases with antiproliferative activity against cancer cells
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A novel series of (7-aryl-1,5-naphthyridin-2-yl)ureas was discovered as dual ERK2 and Aurora B kinases inhibitors. Several analogues were active at micromolar and submicromolar range against ERK2 and Aurora B, associated with very promising antiproliferat
- Defaux, Julien,Antoine, Maud,Logé, Cédric,Le Borgne, Marc,Schuster, Tilmann,Seipelt, Irene,Aicher, Babette,Teifel, Michael,Günther, Eckhard,Gerlach, Matthias,Marchand, Pascal
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p. 3748 - 3752
(2014/09/17)
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- HETEROCYCLIC COMPOUNDS AND USES THEREOF
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Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.
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Paragraph 00143; 00305
(2013/06/06)
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- HETEROCYCLIC COMPOUNDS AND USES THEREOF
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Heterocyclic entities that modulate PI3 kinase activity, pharmaceutical compositions containing the heterocyclic entities, and methods of using these chemical entities for treating diseases and conditions associated with PI3 kinase activity are described herein.
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Page/Page column 39; 75
(2011/12/14)
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- METABOTROPIC GLUTAMATE RECEPTOR MODULATORS
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The invention relates to heterocyclic derivatives as well as their pharmaceutically acceptable salts. The invention further relates to a process for the preparation of such compounds. The compounds of the invention are mGluR5 modulators and are therefore useful for the control and prevention of acute and/or chronic neurological disorders
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Page/Page column 40
(2011/02/24)
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- NOVEL JNK INHIBITORS
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Disclosed are compounds of the formula (I) wherein X is N or CH, and Y is N or CR5. Also disclosed are methods of treating JNK and ERK mediated diseases using the compounds of formula 1.0.
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Page/Page column 108
(2008/12/07)
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- Synthesis and SAR comparison of regioisomeric aryl naphthyridines as potent mGlu5 receptor antagonists
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We describe three novel regioisomeric series of aryl naphthyridine analogs, which are potent antagonists of the Class III GPCR mGlu5 receptor. The synthesis and in vitro and in vivo pharmacological activities of these analogs are discussed.
- Galatsis, Paul,Yamagata, Koji,Wendt, John A.,Connolly, Cleo J.,Mickelson, John W.,Milbank, Jared B.J.,Bove, Susan E.,Knauer, Christopher S.,Brooker, Rachel M.,Augelli-Szafran, Corinne E.,Schwarz, Roy D.,Kinsora, Jack J.,Kilgore, Kenneth S.
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p. 6525 - 6528
(2008/03/18)
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