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

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 (EC50=6 μM), active in-vivo in the Weanling rat model when administered subcutaneously.