نبذة مختصرة : Selective inhibitors of DYRK1A are of interest for the treatment of cancer, Type 2 diabetes and neurological disorders. Optimization of imidazo [1,2-b]pyridazine fragment 1 through structure−activity relationship exploration and in silico drug design efforts led to the discovery of compound 17 as a potent cellular inhibitor of DYRK1A with selectivity over much of the kinome. The binding mode of compound 17 was elucidated with X-ray crystallography, facilitating the rational design of compound 29, an imidazo [1,2-b]pyridazine with improved kinase selectivity with respect to closely related CLK kinases.
Relation: https://orca.cardiff.ac.uk/id/eprint/167926/1/1-s2.0-S0223523424001727-main.pdf; Henderson, Scott, Sorrell, Fiona, Bennett, James, Fedorov, Oleg, Hanley, Marcus https://orca.cardiff.ac.uk/view/cardiffauthors/A24054555.html, Godoi, Paulo, de Sousa, Roberta Ruela, Robinson, Sean, Hopkins Navratilova, Iva, Elkins, Jonathan and Ward, Simon https://orca.cardiff.ac.uk/view/cardiffauthors/A2342916Z.html orcid:0000-0002-8745-8377 orcid:0000-0002-8745-8377 2024. Imidazo[1,2-b]pyridazines as inhibitors of DYRK kinases. European Journal of Medicinal Chemistry 269 , 16292. 10.1016/j.ejmech.2024.116292 https://doi.org/10.1016/j.ejmech.2024.116292 file https://orca.cardiff.ac.uk/id/eprint/167926/1/1-s2.0-S0223523424001727-main.pdf
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