A Simple and Efficient Procedure for the Synthesis of an Alendronate-Oligonucleotide Conjugate Via a Carbamate Linker

Abstract

Alendronate. an munobisphosphonate used clinically for thc treatment of osteoporosis and others bones deseases is a synthetic analog of pyrophosphate in which the labiie phosphoanhydride bond (HO)₂P(O)-O-P(O)(OH)₂ is replaced by a stable hydroxymethylene group (HO), P(O)-C(OH)R-P(O)(OH). The most important action of this bisphosphonate is the inhibition of the bone resorption. The mechanism of action is not completely elucided. One hypothesis is hat thc bisphosphonate act by suppressing osteoclast activity.1] are used for the enzyme inhibition or for the antisens strategy parriculary in oncology The pharmacological interest of these two moieties encouraged us to bind a bisphosphonate at the 5′ OH of an oligonucleotide via a carbarnate bond. In the first time he synthesis conditions have been studied on model alcohol.