Abstract
Clodronate (1) belongs to family of bisphosphonates which are used to inhibit mineralization of soft tissues as well as bone formation and resorption disorders.[I] The clinical use of bisphosphonates is limited due to their poor bióvailability which is mostly attributed to their hydrophilic structure. More lipophilic molecules are obtained if some or all of the anionic sites are converted to covalent bonds. We herein report a new prodrug serie for clodronate: the anhydrides 2 and 3. Previously we have reported that the simple alkyl esters 4 do not release clodronate via chemical or enzymatic hydrolysis.[2] The prepared new derivatives are stable in water (pH 5–7.5) but clodronate isrelased rapidly with enzymatic hydrolysis.
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