Design and synthesis of 2-amino-4-methylpyridine analogues as inhibitors for inducible nitric oxide synthase and in vivo evaluation of [18F]6-(2-fluoropropyl)-4-methyl-pyridin-2-amine as a potential PET tracer for inducible nitric oxide synthase

J Med Chem. 2009 Apr 23;52(8):2443-53. doi: 10.1021/jm801556h.


A series of position-6 substituted 2-amino-4-methylpyridine analogues was synthesized and compounds 9, 18, and 20 were identified as the inhibitors with the greatest potential to serve as PET tracers for imaging inducible nitric oxide synthase (iNOS). [(18)F]9 was synthesized and evaluated in a mouse model of lipopolysaccharide (LPS)-induced iNOS activation. In vivo biodistribution studies of [(18)F]9 indicate higher tracer uptake in the lungs of the LPS-treated mice when compared to control mice. Tracer uptake at 60 min postinjection was reduced in a blocking study using a known inhibitor of iNOS. The expression of iNOS was confirmed by Western blot analysis of lung samples from the LPS-treated mice. MicroPET studies also demonstrated accumulation of radiotracer in the lungs of the LPS-treated mice. Taken collectively, these data suggest that [(18)F]9 shows favorable properties as a PET tracer to image iNOS activation with PET.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aminopyridines / chemical synthesis*
  • Aminopyridines / chemistry
  • Aminopyridines / pharmacokinetics
  • Animals
  • Drug Design
  • Enzyme Activation
  • Fluorine Radioisotopes
  • Lipopolysaccharides / pharmacology
  • Lung / diagnostic imaging
  • Lung / enzymology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / metabolism
  • Positron-Emission Tomography
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism
  • Structure-Activity Relationship
  • Tissue Distribution


  • 6-(2-fluoropropyl)-4-methylpyridin-2-amine
  • Aminopyridines
  • Fluorine Radioisotopes
  • Lipopolysaccharides
  • Radiopharmaceuticals
  • Nitric Oxide Synthase Type II