Discovery of imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors.
The synthesis and structure-activity relationships (SAR) of novel, potent imidazo[1,2-a]pyrazine-based Aurora kinase inhibitors are described. The X-ray crystal structure of imidazo[1,2-a]pyrazine Aurora inhibitor 1j is disclosed. Compound 10i was identified as lead compound with a promising overall profile.
Belanger
David B
DB
Department of Chemistry, Merck Research Laboratories, Cambridge, MA 02141, USA. david.belanger@merck.com
Curran
Patrick J
PJ
Hruza
Alan
A
Voigt
Johannes
J
Meng
Zhaoyang
Z
Mandal
Amit K
AK
Siddiqui
M Arshad
MA
Basso
Andrea D
AD
Gray
Kimberly
K
D064127:Aurora Kinases; D001798:Blood Proteins / Q000378:metabolism; D018360:Crystallography, X-Ray; D055808:Drug Discovery; D005434:Flow Cytometry; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011719:Pyrazines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D001798:Blood Proteins; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011719:Pyrazines; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases