Structure-based design of 3-aryl-6-amino-triazolo[4,3-b]pyridazine inhibitors of Pim-1 kinase.

Article Details

Citation

Grey R, Pierce AC, Bemis GW, Jacobs MD, Moody CS, Jajoo R, Mohal N, Green J

Structure-based design of 3-aryl-6-amino-triazolo[4,3-b]pyridazine inhibitors of Pim-1 kinase.

Bioorg Med Chem Lett. 2009 Jun 1;19(11):3019-22. doi: 10.1016/j.bmcl.2009.04.061. Epub 2009 Apr 20.

PubMed ID
19414255 [ View in PubMed
]
Abstract

A series of substituted 3-aryl-6-amino-triazolo[4,3-b]pyridazines were identified as highly selective inhibitors of Pim-1 kinase. Initial exploration identified compound 24 as a potent, selective inhibitor, limited in its utility by poor solubility and permeability. Understanding the unusual ATP-binding site of the Pim kinases and X-ray crystallographic data on compound 24 led to design improvements in this class of inhibitor. This resulted in compound 29, a selective, soluble and permeable inhibitor of Pim-1.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
6-(5-BROMO-2-HYDROXYPHENYL)-2-OXO-4-PHENYL-1,2-DIHYDROPYRIDINE-3-CARBONITRILESerine/threonine-protein kinase pim-1IC 50 (nM)50N/AN/ADetails
IMIDAZOPYRIDAZIN 1Serine/threonine-protein kinase pim-1IC 50 (nM)61N/AN/ADetails
N-cyclohexyl-3-[3-(trifluoromethyl)phenyl][1,2,4]triazolo[4,3-b]pyridazin-6-amineSerine/threonine-protein kinase pim-1Ki (nM)11N/AN/ADetails