A5103117174- Asymmetric Synthesis and Catalysis
- Organic Chemistry Cycloaddition Reactions
- Chemical Synthesis and Analysis
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Synthetic Organic Chemistry Methods
- Synthesis and bioactivity of alkaloids
- Oxidative Organic Chemistry Reactions
- Synthesis and Catalytic Reactions
- Synthesis of β-Lactam Compounds
- Chemical synthesis and alkaloids
- Cyclopropane Reaction Mechanisms
- Synthesis and Biological Evaluation
- Synthesis and Biological Activity
- Fluorine in Organic Chemistry
- Crystallography and molecular interactions
- Marine Sponges and Natural Products
- Click Chemistry and Applications
- Traditional and Medicinal Uses of Annonaceae
- Synthesis of heterocyclic compounds
- Cancer Research and Treatments
- Cancer Treatment and Pharmacology
- Chemical Synthesis and Reactions
- Peptidase Inhibition and Analysis
- Carbohydrate Chemistry and Synthesis
RWTH Aachen University
2020-2022
Universitätsklinikum Aachen
2020-2022
Radboud University Nijmegen
2002-2020
Lund University
2014
Solvay (Netherlands)
1989-2009
Pondicherry University
2004-2007
University of Liège
2004
University of Groningen
2002
Rotterdam University of Applied Sciences
2001
Nottingham Trent University
2001
A single triggering event in the core of a dendrimer composed two or more generations multiple-release monomeric building blocks can induce release all end groups at termini (see schematic representation). Such systems could find application, for example, field (targeted) drug delivery, where disease- organ-specific activation trigger simultaneous multiple biologically active molecules. Dendrimers are well-defined, branched treelike molecules with groups.1, 2 Numerous applications these...
Synthetic immune-stimulatory drugs such as agonists of the Toll-like receptors (TLR) 7/8 are potent activators antigen-presenting cells (APCs), however, they also induce severe side effects due to leakage from site injection into systemic circulation. Here, we report on design and synthesis an amphiphilic polymer-prodrug conjugate imidazoquinoline TLR7/8 agonist that in aqueous medium forms vesicular structures 200 nm. The contains endosomal enzyme-responsive linker enabling degradation...
The design and synthesis of several novel elongated self-elimination spacer systems for application in prodrugs is described. These can be incorporated between a cleavable specifier the parent drug. Naphthalene- biphenyl-containing spacers were synthesized but did not eliminate. Prodrugs anticancer agents doxorubicin paclitaxel are reported that contain two or three electronic cascade spacers. A catalytic HOBt was found N-aryl carbamates through reacting 4-nitrophenyl carbonate with an...
The nontoxic paclitaxel-2'-carbamate prodrugs 2-5 and paclitaxel-2'-carbonate prodrug 6 were synthesized tested for activation by the tumor-associated enzyme plasmin. A generally applicable method synthesis of paclitaxel-2'-carbamates was developed. In buffer solution, 2, which contained an unsubstituted ethylenediamine spacer, not stable, whereas 3-6 highly stable. Prodrugs showed on average a decrease in cytotoxicity more than 8000-fold comparison with parent drug seven human tumor cell...
Doxorubicin is an anthracycline anticancer agent that commonly used in the treatment of a variety cancers, but its application associated with severe side effects. Biodegradable and thermosensitive polymeric micelles based on poly(ethylene glycol)-b-poly[N-(2-hydroxypropyl) methacrylamide-lactate] (mPEG-b-p(HPMAmLac(n))) have been studied as drug delivery systems for therapeutic imaging agents shown promising vitro vivo results. The purpose this study was to investigate covalent coupling...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThermally catalyzed and noncatalyzed [2 + 2] cycloadditions between ketene acetals carbonyl compounds. A simple route to 2,2-dialkoxyoxetanesHans W. Scheeren, Rene M. Aben, Pieter H. J. Ooms, Rutger F. NivardCite this: Org. Chem. 1977, 42, 19, 3128–3132Publication Date (Print):September 1, 1977Publication History Published online1 May 2002Published inissue 1 September 1977https://doi.org/10.1021/jo00439a005RIGHTS & PERMISSIONSArticle...
New prodrugs of daunorubicin and doxorubicin designed for selective activation by the serine protease plasmin are described. The low toxic 3, 4, 5 converted to corresponding cytotoxic drugs upon proteolysis tumor-associated plasmin. Application a self-eliminating spacer was essential enzyme activation. A prodrug containing chloro-substituted synthesized with aim enhancing rate conversion All were highly stable in buffer solution serum on average 15-fold less than parent seven human tumor...
Background: Enzyme-activatable prodrugs are extensively employed in oncology and beyond.Because enzyme concentrations their (sub)cellular compartmentalization highly heterogeneous different tumor types patients, we propose ultrasound-directed enzyme-prodrug therapy (UDEPT) as a means to increase access availability for prodrug activation locally. Methods:We synthesized β-glucuronidase-sensitive self-immolative doxorubicin with spacer lengths between the active drug moiety capping group.We...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntramolecular Pictet-Spengler reaction of N-alkoxytryptamines. 3. Stereoselective synthesis (-)-debromoeudistomin L and (-)-O-methyldebromoeudistomin E their stereoisomersPedro H. Hermkens, Jan Van Maarseveen, Harry C. J. Ottenheijm, Chris G. Kruse, Hans W. ScheerenCite this: Org. Chem. 1990, 55, 13, 3998–4006Publication Date (Print):June 1, 1990Publication History Published online1 May 2002Published inissue 1 June...
To generate doxorubicin (Dox) specifically at the tumor site, chemotherapeutic agent was incorporated into a prodrug by linkage to peptide recognized plasmin, which is overproduced in many cancers. ST-9905, contains an elongated self-elimination spacer, activated more rapidly vitro plasmin than ST-9802. Prodrug activation depended on level of urokinase produced cells and inhibited aprotinin, inhibitor. Comparison equimolar concentrations ST-9802, Dox EF43.fgf-4 MCF7 models revealed that both...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAntiviral and antitumor structure-activity relationship studies on tetracyclic eudistominesJan H. Van Maarseveen, Pedro Hermkens, Erik De Clercq, Jan Balzarini, Hans W. Scheeren, Chris G. KruseCite this: J. Med. Chem. 1992, 35, 17, 3223–3230Publication Date (Print):August 1, 1992Publication History Published online1 May 2002Published inissue 1 August...
A seven-step solid-phase synthesis of spirohydantoins 7 and an eight-step spiro-2,5-diketopiperazines 8 is reported. Key intermediate in the both compound libraries resin-bound cyclic α,α-disubstituted α-amino ester 5, which can be obtained after selective homogeneous reduction aliphatic nitro 4 using tin(II) chloride dihydrate. Nitro 4, turn, synthesized by a high-pressure-assisted [4 + 2] cycloaddition alkene 2 butadiene 3, whereas Knoevenagel condensation acetate with imine. Novel are...