Discovery of a dihydropyrimidine series of molecules that selectively mimic the biological actions of calcitonin

Bioorg Med Chem Lett. 2004 Mar 8;14(5):1155-9. doi: 10.1016/j.bmcl.2003.12.071.

Abstract

The use of a multiplex mimetic assay led us to identify 1,4-dihydropyrimidines with potent and selective calcitonin receptor mimetic activity. Subsequent modification of the dihydropyrimidine scaffold led to a series of molecules that were efficacious in a neonatal mouse calvaria in vitro model. Dihydropyrimidine 5h, in particular, was identified as a calcitonin mimetic (EC(50)=6 microM), active in-vivo in the Weanling rat model when administered subcutaneously.

MeSH terms

  • Animals
  • Calcitonin / chemistry*
  • Calcitonin / physiology*
  • Calcitonin / urine
  • Cell Line
  • Dihydropyridines / chemistry*
  • Dihydropyridines / pharmacology
  • Dihydropyridines / urine
  • Humans
  • Molecular Mimicry / physiology*
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology
  • Pyrimidines / urine
  • Rats

Substances

  • Dihydropyridines
  • Pyrimidines
  • Calcitonin