922173-23-7Relevant academic research and scientific papers
Development of a self-immolative linker for tetrazine-triggered release of alcohols in cells
Davies, Sarah,Oliveira, Bruno L.,Bernardes, Gon?alo J. L.
supporting information, p. 5725 - 5730 (2019/06/19)
Bioorthogonal decaging reactions are a promising strategy for prodrug activation because they involve bond cleavage to release a molecule of interest. The trans-cyclooctene (TCO)-tetrazine inverse electron-demand Diels-Alder reaction has been widely applied in vivo for decaging of amine prodrugs, however, the release of alcohol-containing bioactive compounds has been less well studied. Here, we report a TCO-carbamate benzyl ether self-immolative linker for the release of OH-molecules upon reaction with a tetrazine trigger. The benzyl ether linker proved to be highly stable and can rapidly liberate alcohols under physiological conditions upon reaction with tetrazines. The mechanism and decaging yield were systematically examined by fluorescence and HPLC analysis by using a fluorogenic TCO-benzyl ether-coumarin probe and different 3,6-substituted tetrazine derivatives. This study revealed that decaging occurs rapidly (t1/2 = 27 min) and the cycloaddition step happens within seconds (t1/2 = 7 s) with reaction rates of ≈100 M-1 s-1. Importantly, the reaction is compatible with living organisms as demonstrated by the decaging of a prodrug of the antibacterial compound triclosan in the presence of live E. Coli, that resulted in complete cell killing by action of the released "OH-active drug". Overall, this work describes a new linker for masking alcohol functionality that can be rapidly reinstated through tetrazine-triggered decaging.
CYCLOPENTAIMIDAZOLONES FOR THE TREATMENT OF CANCER
-
Paragraph 0101; 0103, (2019/10/01)
Provided herein are compounds useful for the treatment of various proliferative diseases. These compounds, as well as pharmaceutically acceptable salts thereof may be formulated in pharmaceutical compositions, and may be used in methods of treatment and/o
Esters Of Glucuronide Prodrugs Of Anthracyclines And Method Of Preparation And Use In Tumor-Selective Chemotherapy
-
Page/Page column 12, (2009/09/25)
The invention relates to novel esters and in particular to some novel esters of glucuronide prodrugs of anthracyclines having tunable water-solubility, their synthesis and use in tumor-selective chemotherapy. It appeared that in the final step in the synt
The azaquinone-methide elimination: Comparison study of 1,6- and 1,4-eliminations under physiological conditions
Erez, Rotem,Shabat, Doron
supporting information; experimental part, p. 2669 - 2672 (2009/02/02)
The azaquinone-methide elimination is a powerful and efficient reaction useful for disassembly of spacers in prodrug systems. We and others have used the spacer-technique to develop dendritic and polymeric self-immolative molecular systems that can disass
SELF-IMMOLATIVE POLYMERS
-
Page/Page column 50; 51, (2008/12/05)
Self-immolative polymers, designed to release a chemical moiety, or a plurality of chemical moieties, upon a pre-determined cleavage event, or sequences of events, are disclosed. The polymers can be simple polymers, comb polymers or branched polymers. Fur
Protecting groups for glucuronic acid: Application to the synthesis of new paclitaxel (taxol) derivatives
El Alaoui, Abdessamad,Schmidt, Frederic,Monneret, Claude,Florent, Jean-Claude
, p. 9628 - 9636 (2007/10/03)
To prepare two new glucuronide conjugates, allyl ester and allyl carbonates were used as protecting groups of the glucuronic moiety. In this way, an aniline glycosyl carbamate spacer linked to the 2′-OH of paclitaxel was obtained. By using palladium chemistry, an efficient one-step removal of all the allyl groups at the end of the synthesis afforded the desired compounds in good yields.
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.
