Synthesis, crystal structure determination, and biological properties of the DNA-dependent protein kinase (DNA-PK) inhibitor 3-cyano-6-hydrazonomethyl-5-(4-pyridyl)pyrid-[1H]-2-one (OK-1035).
The first reported synthesis of the DNA-PK inhibitor 3-cyano-6-hydrazonomethyl-5-(4-pyridyl)pyrid-[1H]-2-one (OK-1035) is described. The structure of OK-1035 was validated by X-ray crystallography. An IC(50) value of 100 microM was determined for inhibition of DNA-PK, and this is approximately 12-fold higher than that reported previously.
Stockley
M
M
Department of Chemistry, Bedson Building, The University, Newcastle upon Tyne NE1 7RU, UK.
Clegg
W
W
Fontana
G
G
Golding
B T
BT
Martin
N
N
Rigoreau
L J
LJ
Smith
G C
GC
Griffin
R J
RJ
D002867:Chromones / Q000494:pharmacology; D018360:Crystallography, X-Ray; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D009025:Morpholines / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011728:Pyridones / Q000737:chemistry / Q000494:pharmacology*
C095985:3-cyano-5-(4-pyridyl)-6-hydrazonomethyl-2-pyridone; D002867:Chromones; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006835:Hydrazones; D009025:Morpholines; D011728:Pyridones; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases