Novel bisphosphonates for calcium-related disorders

Bisphosphonates are drugs used clinically in various calcium-related disorders such as Paget's disease, hypercalcemia of malignancy, and tumor osteolysis and are undergoing clinical trials for osteoporosis. From the results obtained in various clinical studies using conventional bisphosphonates, it appears that there is a need for compounds with a greater margin between the inhibition of bone resorption and the inhibition of mineralization, without an accompanying increase in toxicity, and at the same time, improved oral bioavailability without gastrointestinal side effects. One research strategy to address these problems is the synthesis and evaluation of non-geminal bisphosphonates, bisacylphosphonates. It is concluded that a new generation of calcium-binding compounds with antiresorptive and anticalcification properties have been obtained. In comparison to clinically used bisphosphonates, the new compounds possess very low toxicity and improved bioavailability.