Synthesis And Characterization Of The Bisphosphonate Class Of Anti-osteoporosis Drug Risedronate And Its Derivatives

Bisphosphonates are one kind of the important antiosteoporosis drugs.They are widely used for the treatment of osteoporosis,deformation bone flammation, bone metastases from malignant hypercalcemia and so on.As the bisphosphonate compounds are in-depth studies and widely used on them, three generations of bisphosphonate products have been developed. Risedronate sodium, a third-generation bisphosphonate with pyridyl, is the earliest protein inhibitor of bone absorption on market and its effect was stronger than earlier the first and second-generation products. As a commercial drug, the disadvantage of the risedronate is that four hydroxyls on both phosphorus atoms of it can chelate easily Ca2+and transition metal ions such as Co2+, Ni+, Cu2+, Fe2+, and Cr2+to form complexes or precipitation, so that make it less effective in biological system. In order to overcome this problem, our strategy, based on the parent structure of residronate, is to modify its structure by esterification and cyclization of the hydroxyls of it and bring a hydrophilic group.Based on this strategy, the following research has been down:(1) The risedronate sodium was synthesized for the third-generation bisphosphonates as anti-osteoporosis drugs.(2) To explore complexing capacity between risedronate and metal ions, the risedronate complexes with calcium ion and a serious of transition metal ions were synthesized, and the results indicated that the complexes have a 1:1 ration of ligand and metals, (3) To reasearch risedronate salts for anti-osteoporosis new drugs, three mono-and di-substituted and cyclic derivatives of risedronate were design and synthesized, which are not reported in lectures, and (4) a novel risedronate molecule with fluorescent group was successfully synthesized by a crosslink group which linking risedronate and fluorescent reagent, this will help to investigate the mechanism of the drug. All synthesized compounds were characterized by EA,IR,UV-Vis and 1HNMR and confirmed.