Highly potent geminal bisphosphonates. From pamidronate disodium (Aredia) to zoledronic acid (Zometa)

…, J Schmid, G Schreiber, Y Seltenmeyer…

Index: Widler, Leo; Jaeggi, Knut A.; Glatt, Markus; Mueller, Klaus; Bachmann, Rolf; Bisping, Michael; Born, Anne-Ruth; Cortesi, Reto; Guiglia, Gabriela; Jeker, Heidi; Klein, Remy; Ramseier, Ueli; Schmid, Johann; Schreiber, Gerard; Seltenmeyer, Yves; Green, Jonathan R. Journal of Medicinal Chemistry, 2002 , vol. 45, # 17 p. 3721 - 3738

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Citation Number: 284

Abstract

Bisphosphonates (BPs) are pyrophosphate analogues in which the oxygen in POP has been replaced by a carbon, resulting in a metabolically stable PCP structure. Pamidronate (1b, Novartis), a second-generation BP, was the starting point for extensive SAR studies. Small changes of the structure of pamidronate lead to marked improvements of the inhibition of osteoclastic resorption potency. Alendronate (1c, MSD), with an extra methylene group ...