551919-64-3Relevant academic research and scientific papers
Mining Public Domain Data to Develop Selective DYRK1A Inhibitors
Henderson, Scott H.,Sorrell, Fiona,Bennett, James,Hanley, Marcus T.,Robinson, Sean,Hopkins Navratilova, Iva,Elkins, Jonathan M.,Ward, Simon E.
, p. 1620 - 1626 (2020)
Kinases represent one of the most intensively pursued groups of targets in modern-day drug discovery. Often it is desirable to achieve selective inhibition of the kinase of interest over the remaining ～500 kinases in the human kinome. This is especially true when inhibitors are intended to be used to study the biology of the target of interest. We present a pipeline of open-source software that analyzes public domain data to repurpose compounds that have been used in previous kinase inhibitor development projects. We define the dual-specificity tyrosine-regulated kinase 1A (DYRK1A) as the kinase of interest, and by addition of a single methyl group to the chosen starting point we remove glycogen synthase kinase β (GSK3β) and cyclin-dependent kinase (CDK) inhibition. Thus, in an efficient manner we repurpose a GSK3β/CDK chemotype to deliver 8b, a highly selective DYRK1A inhibitor.
Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5- b]pyridazines for the Treatment of Human African Trypanosomiasis
Tear, Westley F.,Bag, Seema,Diaz-Gonzalez, Rosario,Ceballos-Pérez, Gloria,Rojas-Barros, Domingo I.,Cordon-Obras, Carlos,Pérez-Moreno, Guiomar,García-Hernández, Raquel,Martinez-Martinez, Maria Santos,Ruiz-Perez, Luis Miguel,Gamarro, Francisco,Gonzalez Pacanowska, Dolores,Caffrey, Conor R.,Ferrins, Lori,Manzano, Pilar,Navarro, Miguel,Pollastri, Michael P.
, p. 756 - 783 (2020/02/04)
From a high-throughput screen of 42 44 known human kinases inhibitors, a pyrazolo[1,5-b]pyridazine scaffold was identified to begin optimization for the treatment of human African trypanosomiasis. Previously reported data for analogous compounds against h
Synthesis and evaluation of pyrazolo[1,5-b]pyridazines as selective cyclin dependent kinase inhibitors
Stevens, Kirk L.,Reno, Michael J.,Alberti, Jennifer B.,Price, Daniel J.,Kane-Carson, Laurie S.,Knick, Victoria B.,Shewchuk, Lisa M.,Hassell, Anne M.,Veal, James M.,Davis, Stephen T.,Griffin, Robert J.,Peel, Michael R.
scheme or table, p. 5758 - 5762 (2009/06/18)
A novel series of pyrazolo[1,5-b]pyridazines have been synthesized and identified as cyclin dependant kinase inhibitors potentially useful for the treatment of solid tumors. Modification of the hinge-binding amine or the C(2)- and C(6)-substitutions on the pyrazolopyridazine core provided potent inhibitors of CDK4 and demonstrated enzyme selectivity against VEGFR-2 and GSK3β.
PYRADAZINE COMPOUNDS AS GSK-3 INHIBITORS
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Page 39-40, (2008/06/13)
The present invention relates generally to inhibitors of the kinases, such as GSK3, and more particularly to fused pyradazine compounds according to formula (I) and methods of their use.
