- MODULATORS OF MYC FAMILY PROTO-ONCOGENE PROTEIN
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Disclosed herein are compounds and compositions having potency in the modulation of Myc family proteins. Such compounds and compositions can be used in the treatment of proliferative diseases, such as cancer, or in the treatment of disease where modulation of Myc family proteins is desired. Also disclosed herein are methods of using said compounds and compositions.
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Paragraph 00144
(2020/09/08)
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- Scaffold-Hopping and Structure-Based Discovery of Potent, Selective, And Brain Penetrant N-(1H-Pyrazol-3-yl)pyridin-2-amine Inhibitors of Dual Leucine Zipper Kinase (DLK, MAP3K12)
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Recent data suggest that inhibition of dual leucine zipper kinase (DLK, MAP3K12) has therapeutic potential for treatment of a number of indications ranging from acute neuronal injury to chronic neurodegenerative disease. Thus, high demand exists for selective small molecule DLK inhibitors with favorable drug-like properties and good CNS penetration. Herein we describe a shape-based scaffold hopping approach to convert pyrimidine 1 to a pyrazole core with improved physicochemical properties. We also present the first crystal structures of DLK. By utilizing a combination of property and structure-based design, we identified inhibitor 11, a potent, selective, and brain-penetrant inhibitor of DLK with activity in an in vivo nerve injury model.
- Patel, Snahel,Harris, Seth F.,Gibbons, Paul,Deshmukh, Gauri,Gustafson, Amy,Kellar, Terry,Lin, Han,Liu, Xingrong,Liu, Yanzhou,Liu, Yichin,Ma, Changyou,Scearce-Levie, Kimberly,Ghosh, Arundhati Sengupta,Shin, Young G.,Solanoy, Hilda,Wang, Jian,Wang, Bei,Yin, Jianping,Siu, Michael,Lewcock, Joseph W.
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p. 8182 - 8199
(2015/11/09)
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- 3-SUBSTITUTED PYRAZOLES AND USE AS DLK INHIBITORS
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The present invention provides for compounds of Formula (I) and various embodiments thereof, and compositions comprising compounds of Formula (I) and various embodiments thereof. (I) In compounds of Formula I, the groups R1, R2, R3, R4, R5, R6 and R7 have the meaning as described herein. The present invention also provides for methods of using compounds of Formula I and compositions comprising compounds of Formula (I) as DLK inhibitors and for treating neurodegeneration diseases and disorders.
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- Substituted pyrazoloquinazolinones and pyrroloquinazolinones as allosteric modulators of group II metabotropic glutamate receptors
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The present invention relates to the pyrazoloquinazolinone and pyrroloquinazolinone derivatives of the general formula (I), as well as pharmaceutical compositions containing them, and their use in the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals, in particular their use in the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders.
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Paragraph 0369
(2014/01/07)
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- SUBSTITUTED PYRAZOLOQUINAZOLINONES AND PYRROLOQUINAZOLINONES AS ALLOSTERIC MODULATORS OF GROUP II METABOTROPIC GLUTAMATE RECEPTORS
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The present invention relates to the pyrazoloquinazolinone and pyrroloquinazolinone derivatives of the general formula (I), as well as pharmaceutical compositions containing them, and their use in the treatment and/or prophylaxis of conditions associated with altered glutamatergic signalling and/or functions, and/or conditions which can be affected by alteration of glutamate level or signalling in mammals, in particular their use in the treatment and/or prophylaxis of acute and chronic neurological and/or psychiatric disorders.
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Page/Page column 94; 131
(2014/01/07)
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- PYRAZOLE [3, 4-B] PYRIDINE RAF INHIBITORS
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Compounds of Formula I are useful for inhibition of Raf kinases. Methods of using compounds of Formula I and stereoisomers, tautomers, prodrugs and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
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Page/Page column 123
(2009/10/22)
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