Studies on Novel Bone Resorption Inhibitors. I. Synthesis and Pharmacological Activities of Aminomethylenebisphosphonate Derivatives

A series of aminomethylenebisphosphonate derivatives was synthesized and evaluated for their antiresorptive activities using a parathyroid hormone (PTH)-induced hypercalemia model in rats (PIH model). Among these compounds, (cycloheptylamino)methylenebis(phosphonic acid) (3j) was finally selected for further investigation, proving 10-fold as potent as pamidronate in the PIH model and an immobilization bone atrophy model in rats (DA model). The structure-activity relationships of this series of bisphosphonates are discussed.