A5105930385- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Hormonal Regulation and Hypertension
- Neuroscience and Neuropharmacology Research
- Pharmacogenetics and Drug Metabolism
- Estrogen and related hormone effects
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Neuroethics, Human Enhancement, Biomedical Innovations
- Antibiotic Resistance in Bacteria
- Neurobiology and Insect Physiology Research
- Catalytic Alkyne Reactions
- Bacterial biofilms and quorum sensing
- Law, AI, and Intellectual Property
- Ethics and Social Impacts of AI
- Nicotinic Acetylcholine Receptors Study
- Chemical Synthesis and Reactions
- Ubiquitin and proteasome pathways
- Bacterial Genetics and Biotechnology
- Asymmetric Hydrogenation and Catalysis
- Photoreceptor and optogenetics research
- Chemical Synthesis and Analysis
- Inflammatory mediators and NSAID effects
- Psychology of Moral and Emotional Judgment
- Catalysis for Biomass Conversion
Boehringer Ingelheim (Austria)
2017-2024
Johannes Gutenberg University Mainz
2023
Merck (Germany)
2022-2023
Grünenthal Group (Germany)
2018
University of Copenhagen
2010-2014
Boehringer Ingelheim (Germany)
2014
Saarland University
2006-2012
Helmholtz Institute for Pharmaceutical Research Saarland
2012
Max Planck Institute for Informatics
2008
University of Bologna
2008
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNon-Steroid Anti-Inflammatory AgentsT. Y. Shen, T. B. Windholz, A. Rosegay, E. Witzel, N. Wilson, J. D. Willett, W. Holtz, R. L. Ellis, Matzuk, S. Lucas, C. H. Stammer, F. Holly, Sarett, Risley, G. Nuss, and WinterCite this: Am. Chem. Soc. 1963, 85, 4, 488–489Publication Date (Print):February 1, 1963Publication History Published online1 May 2002Published inissue 1 February...
2-Heptyl-4-hydroxyquinoline (HHQ) and Pseudomonas quinolone signal (PQS) are involved in the regulation of virulence factor production biofilm formation aeruginosa. PqsD is a key enzyme biosynthesis these molecules. Using ligand-based approach, we have identified first class inhibitors. Simplification rigidization led to fragments with high ligand efficiencies. These small molecules repress HHQ PQS P. This validates as target for development anti-infectives.
Abstract Several alcoholysis catalysts, known to be effective for reactions between simple alcohols and soybean oil, were evaluated found ineffective toward of ethylene glycol with oil under traditional reaction conditions. An initial survey alternative catalysts revealed that organometallic tin complexes but unsatisfactory due toxicity difficulty in recovering the catalyst. Satisfactory performance several was achieved calcium carbonate even though at higher temperatures, typically greater...
Pyridine substituted naphthalenes (e.g., I-III) constitute a class of potent inhibitors aldosterone synthase (CYP11B2). To overcome the unwanted inhibition hepatic enzyme CYP1A2, we aimed at reducing number aromatic carbons these molecules because aromaticity has previously been identified to correlate positively with CYP1A2 inhibition. As hypothesized, tetrahydronaphthalene type molecular scaffold (1-11) exhibit decreased However, tetralone 9 turned out be cytotoxic human cell line U-937...
CYP11B1 inhibition is a promising therapy for Cushing's syndrome. Starting from etomidate, references I and II, the title compounds were designed synthesized. Cyclopropyl analogue 4 was identified as inhibitor more potent (IC(50) = 2.2 nM) than leads selective (SF 11) metyrapone. Since it also showed of rat good selectivity over human CYP17 CYP19, candidate further development.
Pyridine substituted 3,4-dihydro-1H-quinolin-2-ones (e.g., 1−3) constitute a class of highly potent and selective inhibitors aldosterone synthase (CYP11B2), promising target for the treatment hyperaldosteronism, congestive heart failure, myocardial fibrosis. Among these, ethyl-substituted 3 possesses high selectivity against CYP1A2. Rigidification by incorporation ethyl group into 5- or 6-membered ring affords compounds with pyrroloquinolinone pyridoquinolinone molecular scaffold 4 5). It...
Pharmacophore modeling of a series aldosterone synthase (CYP11B2) inhibitors triggered the design compounds 11 and 12 by extending previously established naphthalene molecular scaffold (e.g., present in molecules 1 2) via introduction phenyl or benzyl residue 3-position. These additional aromatic moieties have been hypothesized to fit into newly identified hydrophobic pharmacophore feature HY3. Subsequent docking studies our refined CYP11B2 protein model performed prior synthesis estimate...
Targeting quorum sensing: The Pseudomonas quinolone signal (PQS) and its direct precursor HHQ are important quorum-sensing molecules in P. aeruginosa that contribute to the pathogenicity of this bacterium. In vitro reconstitution biosynthesis employing recombinant PqsD protein has shed light on enzyme substrates, led a test system for identifying inhibitors. Detailed facts importance specialist readers published as "Supporting Information". Such documents peer-reviewed, but not copy-edited...
Recently, we reported on the development of potent and selective inhibitors aldosterone synthase (CYP11B2) for treatment congestive heart failure myocardial fibrosis. A major drawback these nonsteroidal compounds was a strong inhibition hepatic drug-metabolizing enzyme CYP1A2. In present study, examined influence substituents in heterocycle lead structures with naphthalene molecular scaffold to overcome this unwanted side effect. With respect CYP11B2 inhibition, some induced dramatic...
Abstract The rapid and dynamic nature of digital transformation challenges companies that wish to develop deploy novel technologies. Like other actors faced with this transformation, need find robust ways ethically guide their innovations business decisions. Digital ethics has recently featured in a plethora both practical corporate guidelines compilations high-level principles, but there remains gap concerning the development sound ethical guidance specific contexts. As multinational...
Allenyl carbinols undergo regioselective hydrostannation in the presence of MoBl3, a catalyst originally developed for alkynes, giving rise to allyl stannanes. These stannanes can easily be converted into useful synthetic building blocks such as iodides or vinyl epoxides.
Identifying promising chemical starting points for small molecule inhibitors of active, GTP-loaded KRAS "on" remains great importance to clinical oncology and represents a significant challenge in medicinal chemistry. Here, we describe broadly applicable learnings from hit finding campaign: While initially identified biochemical high-throughput screen, later discovered that compound potencies were all but assay artifacts linked metal salts interfering with AlphaScreen technology. The source...
Argiotoxin-636 (ArgTX-636), a natural product from the spider Argiope lobata, is potent but nonselective open-channel blocker of ionotropic glutamate (iGlu) receptors. Here, three series analogues were designed to exploit selectivity among iGlu receptors, taking advantage recently developed solid-phase synthetic methodology for synthesis ArgTX-636 and analogues. Initially, importance secondary amino groups in polyamine chain was studied by systematically modified analogues, which evaluated...
The <i>α</i>-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are glutamate-gated cation channels that mediate fast excitatory synaptic transmission in the central nervous system. AMPARs tetramers formed by homo- or heteromeric assembly of GluA1–4 subunits to produce multiple subtypes with varying biophysical properties. Polyamine toxins such as joro spider toxins, philanthotoxins (PhTXs), and argiotoxins use-dependent ion channel blockers widely employed highly potent...
Mo(CO)3(CNt-Bu)3 (MoBI3) was found to be a suitable catalyst for the regioselective hydrostannation of several types alkynes, especially propargyl alcohol derivatives, affording preferentially α-stannylated products. If propargylic acetates are used, stannylated allylic produced substrates Pd-catalyzed alkylations. Allenyl carbinols also undergo in presence MoBI3, because allenyl more reactive than and therefore milder reaction conditions possible. Allylstannanes formed preferentially, which...
Certain spiders contain large pools of polyamine toxins, which are putative pharmacological tools awaiting further discovery. Here we present a general synthesis strategy for this class toxins and prepare five structurally varied toxins. Electrophysiological testing at three ionotropic glutamate receptor subtypes reveals that two these, Nephila 1 (NPTX-1) 8 (NPTX-8), comprise intriguing activities by having subnanomolar IC50 values kainate receptors.
Polyamine toxins from orb weaver spiders are attractive pharmacological tools particularly for studies of ionotropic glutamate (iGlu) receptors in the brain. These polyamine biosynthesized a combinatorial manner, providing plethora related, but structurally complex to be exploited biological studies. Here, we have used solid-phase synthetic methodology efficient synthesis Joro spider toxin-4 (JSTX-4) (1) Nephila clavata, sufficient amounts toxin evaluation at iGlu receptor subtypes using...
Abstract Psychological literature indicates that actions performed with the assistance of cognition‐enhancing biomedical technologies are often deemed to be less praiseworthy than similar without such assistance. This study examines (i) whether this result extends bioenhancement moral capacities, and (ii) if so, what explains effect on perceived praiseworthiness. The findings indicate facilitated by morally bioenhanced individuals considered deserving praise ‘traditional’ enhancement—for...
Abstract Recent attempts to develop and apply digital ethics principles address the challenges of transformation leave organisations with an operationalisation gap. To successfully implement such guidance, they must find ways translate high-level frameworks into practical methods tools that match their specific workflows needs. Here, we describe development a standardised risk assessment tool, Principle-at-Risk Analysis (PaRA), as means close this gap for key level infrastructure at many –...