3VAP

Synthesis and SAR Studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off target kinase selectivity

Summary for 3VAP

• Entry DOI: 10.2210/pdb3vap/pdb
• Descriptor: Aurora kinase A, 3-(1-{2-[(3-fluoropyridinium-4-yl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)-6-methyl-8-[(3-{[(1R,3R)-3-methylpiperidinium-1-yl]methyl}-1,2-thiazol-5-yl)amino]imidazo[1,2-a]pyrazin-1-ium (2 entities in total)
• Functional Keywords: kinase, cell cycle, inhibitor, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm, cytoskeleton, centrosome: O14965
• Total number of polymer chains: 1
• Total formula weight: 32003.82

Authors

Voss, M.E.,Rainka, M.P.,Fleming, M.,Peterson, L.H.,Belanger, D.B.,Siddiqui, M.A.,Hruza, A.,Voigt, J.,Basso, A.D.,Gray, K. (deposition date: 2011-12-29, release date: 2012-05-02, Last modification date: 2024-02-28)

Primary citation

Voss, M.E.,Rainka, M.P.,Fleming, M.,Peterson, L.H.,Belanger, D.B.,Siddiqui, M.A.,Hruza, A.,Voigt, J.,Gray, K.,Basso, A.D.
Synthesis and SAR studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off-target kinase selectivity.
Bioorg.Med.Chem.Lett., 22:3544-3549, 2012

PubMed Abstract: The structure-activity relationships of new Aurora A/B kinase inhibitors derived from the previously identified kinase inhibitor 12 are described. Introduction of acetic acid amides onto the pyrazole of compound 12 was postulated to influence Aurora A/B selectivity and improve the profile against off-target kinases. The SAR of the acetic acid amides was explored and the effect of substitution on enzyme inhibition as well as mechanism-based cell activity was studied. Additionally, several of the more potent inhibitors were screened for their off-target kinase selectivity.

PubMed: 22503250
DOI: 10.1016/j.bmcl.2012.03.051

Experimental method

X-RAY DIFFRACTION (2.66 Å)