Synthesis of new alendronate analogs for bone-targeted drug delivery strategies

Abstract

1-Hydroxymethylene-1,1-bisphosphonate (HMBP) derivatives are widely used for the treatment of bone disorders and for bone imagery. Through their high affinity for bone matrix hydroxyapatite, they have shown promising development as powerful bone vectors for many bioactive compounds. To improve the toolbox of conjugatable bisphosphonates, we reported here a convenient synthesis of alendronate derivatives bearing tunable functions on their side chain. The developed straightforward synthetic strategy provides substituted 1-aminoalkyl-1-hydroxymethylene-1,1-bisphosphonates (N-HMBPs) for conjugation strategies.