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)

Bioorg Med Chem Lett. 2001 Nov 5;11(21):2837-41. doi: 10.1016/s0960-894x(01)00537-6.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromones / pharmacology
  • Crystallography, X-Ray
  • DNA-Activated Protein Kinase
  • DNA-Binding Proteins*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Models, Molecular
  • Morpholines / pharmacology
  • Protein Serine-Threonine Kinases / antagonists & inhibitors*
  • Pyridones / chemistry
  • Pyridones / pharmacology*

Substances

  • 3-cyano-5-(4-pyridyl)-6-hydrazonomethyl-2-pyridone
  • Chromones
  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Hydrazones
  • Morpholines
  • Pyridones
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • DNA-Activated Protein Kinase
  • Protein Serine-Threonine Kinases