Metabolites of orally active NO-independent pyrazolopyridine stimulators of soluble guanylate cyclase

Bioorg Med Chem. 2002 Jun;10(6):1711-7. doi: 10.1016/s0968-0896(02)00034-2.

Abstract

The pyrazolopyridine stimulators of soluble guanylate cyclase BAY 41-2272 and 41-8543 were oxidised in rats and dogs at their 5-pyrimidinyl-cyclopropyl and -morpholino residue. These metabolites activate the soluble guanylate cyclase, induce vasoelaxation and thereby may contribute to the in vivo activity of BAY 41-2272 and BAY 41-8543.

MeSH terms

  • Administration, Oral
  • Animals
  • Aorta / drug effects
  • Blood Pressure / drug effects
  • Crystallography, X-Ray
  • Dogs
  • Enzyme Activation / drug effects
  • Guanylate Cyclase / chemistry
  • Guanylate Cyclase / metabolism*
  • In Vitro Techniques
  • Injections, Intravenous
  • Lung / drug effects
  • Lung / enzymology
  • Molecular Structure
  • Morpholines / administration & dosage
  • Morpholines / blood
  • Morpholines / metabolism*
  • Morpholines / pharmacology*
  • Nitric Oxide / metabolism
  • Pyrazoles / administration & dosage
  • Pyrazoles / blood
  • Pyrazoles / metabolism*
  • Pyrazoles / pharmacology*
  • Pyridines / administration & dosage
  • Pyridines / blood
  • Pyridines / metabolism*
  • Pyridines / pharmacology*
  • Pyrimidines / administration & dosage
  • Pyrimidines / blood
  • Pyrimidines / metabolism*
  • Pyrimidines / pharmacology*
  • Rats
  • Rats, Wistar
  • Solubility
  • Vasodilation / drug effects

Substances

  • 3-(4-Amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo(3,4-b)pyridine
  • BAY 41-8543
  • Morpholines
  • Pyrazoles
  • Pyridines
  • Pyrimidines
  • pyrazolopyridine
  • Nitric Oxide
  • Guanylate Cyclase