title: Synthesis and SAR studies of imidazo-[1,2-a]-pyrazine Aurora kinase inhibitors with improved off-target kinase selectivity.
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.
authors.affiliation: AMRI Global, 26 Corporate Circle, Albany, NY 12212, USA. matthew.voss@amriglobal.com
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Voss
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Rainka
authors.forename: Mike
authors.initials: M
authors.lastname: Fleming
authors.forename: Lisa H
authors.initials: LH
authors.lastname: Peterson
authors.forename: David B
authors.initials: DB
authors.lastname: Belanger
authors.forename: M Arshad
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: Alan
authors.initials: A
authors.lastname: Hruza
authors.forename: Johannes
authors.initials: J
authors.lastname: Voigt
authors.forename: Kimberly
authors.initials: K
authors.lastname: Gray
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Basso
mesh_terms: D064127:Aurora Kinases; D018360:Crystallography, X-Ray; D007093:Imidazoles / Q000494:pharmacology*; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011719:Pyrazines / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; C556838:imidazo(1,2-a)pyrazine; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases