Add time:08/07/2019         Source:sciencedirect.com

The synthesis and preliminary evaluation of novel alkyl and acyloxymethyl esters of etidronic acid as etidronate prodrugs is reported. Tetramethyl ester of etidronic acid was found be isomerized at pH 7.4 and P–C–P bridge was rearranged to P–C–O–P. This unwanted process was prevented via acylation of the bridging carbon’s alcohol group. Acylation showed to be stable if one or more phosphonic OH– groups were substituted. However, when none of the phosphonic OH– groups were substituted, the acylation was chemically hydrolysed and the parent drug was released. This finding was successfully applied in the design of tetrapivaloyloxymethyl ester of acetylated etidronic acid which released etidronic acid via enzymatic (first step) and chemical (second step) hydrolysis in liver homogenate. However, the corresponding tri-substituted pivaloyloxymethyl ester having adequate water-solubility and lipophilicity (log Papp 0.6 at pH 7.4), is probably the most potential prodrug candidate reported to enhance the oral bioavailability of etidronate.

We also recommend Trading Suppliers and Manufacturers of 5-(1-Hydroxyethylidene)-2-methyl-1,3-cyclopentadiene-1,3-dicarboxylic acid dimethyl ester (cas 14374-51-7). Pls Click Website Link as below: cas 14374-51-7 suppliers