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  • Title: Synthesis and in vivo bioactivity of lipophilic alendronate derivatives against osteoporosis.
    Author: Lu TL, Hu HJ, Zhao W, Chen T.
    Journal: Drug Dev Ind Pharm; 2011 Jun; 37(6):656-63. PubMed ID: 21449707.
    Abstract:
    New lipophilic alendronate amidated derivatives anchored alkyl chains (C(n)H(2n+1), n = 12, 14, 16, 18) had been obtained through the reaction of alendronate with carboxylic acid under anhydrous condition. The physicochemical parameters, such as the solubility and partition coefficient P(o/w) in n-octanol/water, were determined through calculation by performing reversion phase high-performance liquid chromatography (RP-HPLC). The results showed that the derivatives had improved lipophilicity compared with alendronate. The in vivo bioactivities of the derivatives were investigated using the hindlimb unloading growing rats' model. The results showed that the derivatives had in vivo bioactivity against hindlimb unloading growing rats' bone loss, which indicated that the lipophilic derivative would be a promising new potent bisphosphates for treatment of the osteoporosis.
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