Novel non-benzimidazole chk2 kinase inhibitors.
In a recent paper, [Arienti, K. L.; Brunmark, A.; Axe, F. U.; McClure, K. M.; Lee, A.; Blevitt, J.; Neff, D. K.; Huang, L.; Crawford, S.; Chennagiri, R. P.; Karlsson, L.; Brietenbucher, J. G. J. Med. Chem.2005, 48, 1873], we described the discovery of a class of benzimidazole chk2 kinase inhibitors, exemplified by compound 1, which had radio-protective effects in human T-cells subjected to ionizing radiation. Here, a series of non-benzimidazole analogs intended to define the scope of the SAR about this new series of inhibitor, and allow for refinement of the binding model of these compounds to the chk2 kinase is described.
McClure
Kelly J
KJ
Johnson and Johnson Pharmaceutical Research and Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, USA. kmcclure@prdus.jnj.com
Huang
Liming
L
Arienti
Kristen L
KL
Axe
Frank U
FU
Brunmark
Anders
A
Blevitt
Jon
J
Breitenbucher
J Guy
JG
D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology; D064447:Checkpoint Kinase 2; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011837:Radiation-Protective Agents / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D011837:Radiation-Protective Agents; D064447:Checkpoint Kinase 2; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases