Bisphosphonates and novel related structural classes for bone resorption disorders

Bisphosphonates (BPs) are powerful inhibitors of bone resorption. They exert a strong affinity to bone mineral which allows the rapid and selective targeting to bone in vivo. We synthesized and evaluated two new classes of compounds: phosphono succinic acid (PSA) and phosphono glutaric acid (PGA) derivatives. In order to transfer the antiresorptive properties of bisphosphonates attempts have been made to elucidate the key elements of the putative BP pharmacophore. Whereas the new compounds revealed similar or better bone mineral affinity properties than BPs in vitro, the inhibition of endogenous bone resorption in vivo was less effective, but in contrast to BPs the effects were reversible after discontinuation of treatment, which suggests that these compounds are metabolically degradable.