1620575-55-4Relevant academic research and scientific papers
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)
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.
, p. 8182 - 8199 (2015)
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.
3-SUBSTITUTED PYRAZOLES AND USE AS DLK INHIBITORS
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Page/Page column 154, (2014/08/06)
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.
