107038-96-0Relevant academic research and scientific papers
Chloromethyl Glycosides as Versatile Synthons to Prepare Glycosyloxymethyl-Prodrugs
Boltje, Thomas J.,Derks, Maik G. N.,Elferink, Hidde,Rutjes, Floris P. J. T.,Titulaer, Willem H. C.,Veeneman, Gerrit H.
, (2022/01/31)
This work investigates the addition of monosaccharides to marketed drugs to improve their pharmacokinetic properties for oral absorption. To this end, a set of chloromethyl glycoside synthons were developed to prepare a variety of glycosyloxymethyl-prodrugs derived from 5-fluorouracil, thioguanine, propofol and losartan. Drug release was studied in vitro using β-glucosidase confirming rapid conversion of the monosaccharide prodrugs to release the parent drug, formaldehyde and the monosaccharide. To showcase this prodrug approach, a glucosyloxymethyl conjugate of the tetrazole-containing drug losartan was used for in vivo experiments and showed complete release of the drug in a dog-model.
