184579-83-7Relevant academic research and scientific papers
POLYMERIC MICELLES COMPRISING GLUCURONIDE-PRODRUGS
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, (2022/02/06)
The invention relates to a polymeric micelle comprising a block copolymer comprising a polyethylene glycol (PEG) hydrophilic block and a hydrophobic block, and a compound according to formula (I) or formula (III) encapsulated within said polymeric micelle and to uses thereof.
A methylester of the glucuronide prodrug DOX-GA3 for improvement of tumor-selective chemotherapy
Graaf, Michelle De,Nevalainen, Tapio J.,Scheeren, Hans W.,Pinedo, Herbert M.,Haisma, Hidde J.,Boven, Epie
, p. 2273 - 2281 (2007/10/03)
The glucuronide prodrug of doxorubicin, DOX-GA3, can be selectively activated in tumors by extracellular human β-glucuronidase, resulting in a better therapeutic index than doxorubicin. DOX-GA3, however, is rapidly excreted by the kidney. We hypothesized
Novel anthracycline-spacer-β-glucuronide, -β-glucoside, and -β-galactoside prodrugs for application in selective chemotherapy
Leenders, Ruben G. G.,Damen, Eric W. P.,Bijsterveld, Edward J. A.,Scheeren, Hans W.,Houba, Pieter H. J.,Van Der Meulen-Muileman, Ida H.,Boven, Epie,Haisma, Hidde J.
, p. 1597 - 1610 (2007/10/03)
A series of anthracycline prodrugs containing an immolative spacer was synthesized for application in selective chemotherapy. The prodrugs having the general structure anthracycline-spacer-β-glycoside were designed to be activated by β-glucuronidase or β-galactosidase. Prodrugs with -chloro, -bromo or -n-hexyl substituents on the spacer were synthesized as well as prodrugs containing a -β-glucuronyl, -β-glucosyl or -β-galactosyl carbamate specifier. The key step in the synthesis of all prodrugs is the highly β-diastereoselective addition reaction of the anomeric hydroxyl of a glycosyl donor to a spacer isocyanate resulting in the respective β-glycosyl carbamate pro-moieties. The resulting protected pro-moieties were coupled to an anthracycline. Prodrugs were evaluated with respect to activation rate by the appropriate enzyme and additionally, their IC50 values were determined. Optimal prodrugs in this study were at least 100- to 200-fold less toxic than their corresponding drug in vitro and were activated to the parent drug in a half-life time of approximately 2h. Copyright (C) 1999 Elsevier Science Ltd.
Highly diastereoselective synthesis of anomeric β-O-glycopyranosyl carbamates from isocyanates
Leenders, Ruben G. G.,Ruytenbeek, Rob,Damen, Eric W. P.,Scheeren, Hans W.
, p. 1309 - 1312 (2007/10/03)
1-β-O-Glycopyranosyl carbamates are prepared with practically 100% β-diastereoselectivity from anomerically unprotected glycopyranosides and isocyanates. The isocyanates are prepared in situ from carboxylic acids via acyl azides.
