The Design and Synthesis of Bone-Active Phosphinic Acid Analogues: I. the Pyridylaminomethane Phosphonoalkylphosphinates

Cellular and molecular mechanisms of action of bisphosphonates

“…This is supported by the finding that alendronate, risedronate, ibandronate, olpadronate, and pamidronate (but not clodronate) dose-dependently inhibit FPP synthase and/or IPP isomerase, with the order of potency matching the order of antiresorptive potency. 39,41 It is important to note that this confirms our proposal that the two phosphonates groups have a dual purpose, 39,44 being required for the molecular mechanism of action as well as for targeting to bone mineral. 9).…”

“…40 Ebetino et al demonstrated that conversion of an -OH group to a CH 3 group on one of the phosphonate groups (Fig. 41 The conversion of a -OH group to a -CH 3 group on both phosphonate moieties (to form a bisphosphinate) resulted in complete loss of bone affinity and the inability to inhibit bone resorption. 41 The conversion of a -OH group to a -CH 3 group on both phosphonate moieties (to form a bisphosphinate) resulted in complete loss of bone affinity and the inability to inhibit bone resorption.…”

The Kabachnik–Fields reaction: synthetic potential and the problem of the mechanism

“…For example, a phosphite and a phosphonite participate in a one-pot synthesis of phosphonatophosphinate 41. 153 The drawback of this method is that it gives, along with asymmetrical phosphonatophosphinates, a small amount of symmetrical bisphosphonates and bisphosphinates. This can be avoided if phosphorus-containing groups are introduced successively.…”