A5025600261- Adenosine and Purinergic Signaling
- Synthesis and Biological Evaluation
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Click Chemistry and Applications
- Chemical Synthesis and Analysis
- Pharmacological Receptor Mechanisms and Effects
- Chemokine receptors and signaling
- Synthesis and biological activity
- Neuroendocrine Tumor Research Advances
- Receptor Mechanisms and Signaling
- Trypanosoma species research and implications
- Neuropeptides and Animal Physiology
- Pneumocystis jirovecii pneumonia detection and treatment
- Bipolar Disorder and Treatment
- Pharmaceutical Practices and Patient Outcomes
- Carbohydrate Chemistry and Synthesis
- Cell Image Analysis Techniques
- Complementary and Alternative Medicine Studies
- Neuroscience and Neuropharmacology Research
- Research on Leishmaniasis Studies
- Synthesis of β-Lactam Compounds
- Antibiotic Use and Resistance
- S100 Proteins and Annexins
- Synthesis and Catalytic Reactions
University of Münster
2013-2025
University of Tübingen
2024-2025
University of Bonn
2019-2024
Siemens (Germany)
2024
National Institute of Diabetes and Digestive and Kidney Diseases
2016-2019
National Institutes of Health
2016-2019
The P2X4 receptor is implicated in various pathological conditions, including neuropathic pain and cancer. This study reports the development of 1,4-naphthodiazepinedione-based antagonists aimed at both therapeutic applications potential use as PET tracers for imaging expression Structure–activity relationship studies aided by docking molecular dynamics simulations led to a series compounds with potent antagonism, promising vitro inhibition interleukin-1β release THP-1 cells suitability...
Cluster of differentiation 73 (CD73) converts adenosine 5′-monophosphate to immunosuppressive adenosine, and its inhibition was proposed as a new strategy for cancer treatment. We synthesized 5′-O-[(phosphonomethyl)phosphonic acid] derivatives purine pyrimidine nucleosides, which represent nucleoside diphosphate analogues, compared their CD73 inhibitory potencies. In the adenine series, most ribose modifications 1-deaza 3-deaza were detrimental, but 7-deaza tolerated. Uracil substitution...
UDP and UDP-glucose activate the P2Y14 receptor (P2Y14R) to modulate processes related inflammation, diabetes, asthma. A computational pipeline suggested alternatives naphthalene of a previously reported P2Y14R antagonist (3, PPTN) using docking molecular dynamics simulations on hP2Y14R homology model based P2Y12R structures. By reevaluating binding 3 computationally, two alternatives, i.e., alkynyl triazolyl derivatives, were identified. Improved synthesis fluorescent 4 enabled affinity...
Drug development efforts that focused on single targets failed to provide effective treatment for Alzheimer's disease (AD). Therefore, we designed cholinesterase inhibition (ChEI)-based multi-target-directed ligands (MTDLs) simultaneously target AD-related receptors. We built a library of 70 compounds, sequentially screened ChEI, and determined σ1R, σ2R, NMDAR-GluN2B binding affinities, P2X7R antagonistic activities. Nine fulfilled in silico drug-likeness criteria did not display toxicity...
A rapid synthesis of thiophene-based TAK-779 analogues 1 is reported using a late-stage diversification strategy. At the end synthesis, key building block 2, which was prepared in six steps from thiophene, arylated regioselectively at α-position directly with iodoarenes. Since 2 offers several reactive positions, various established catalyst systems were tested. It found that Crabtree (an Ir catalyst) converted efficiently and selectively thiophene system into 2-aryl-substituted compounds 9....
Neglected tropical diseases remain among the most critical public health concerns in Africa and South America. The drug treatments for these are limited, which invariably leads to fatal cases. Hence, there is an urgent need new antitrypanosomal drugs. To address this issue, a large number of diverse heterocyclic compounds were prepared. Straightforward synthetic approaches tolerated pre-functionalized structures, giving rise structurally set analogs. We report on 57 with selective activity...
We recently reported N4-substituted 3-methylcytidine-5′-α,β-methylenediphosphates as CD73 inhibitors, potentially useful in cancer immunotherapy. now expand the structure–activity relationship of pyrimidine nucleotides human inhibitors. 4-Chloro (MRS4598 16; Ki = 0.673 nM) and 4-iodo (MRS4620 18; 0.436 substitution N4-benzyloxy group decreased by ∼20-fold. Primary alkylamine derivatives coupled through a p-amido with varying methylene chain length (24 25) were functionalized congeners, for...
Abstract Ecto-5’-nucleotidase (CD73) is a potential new drug target for cancer immunotherapy. Its overexpression associated with various aggressive cancers, including triple-negative breast (TNBC) and pancreatic cancer, making it promising diagnostic imaging. Besides antibodies, small molecule CD73 inhibitors have been developed are currently in clinical trials. This study aimed to develop evaluate fluorine-18 labeled high-affinity as tracers the non-invasive positron emission tomography...
High-content and high-throughput digital microscopes have generated large image sets in biological experiments clinical practice. Automatic analysis techniques, such as cell counting, are high demand. Here, counting was treated a regression problem using features (phenotypes) extracted by deep learning models. Three convolutional neural network models were developed to regress their counts an end-to-end way. Theoretically, ensembling imaging phenotypes should better representative ability...
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system that characterized by progressive loss oligodendrocytes and myelin associated with thalamic dysfunction. Cuprizone (CPZ)-induced general demyelination in rodents valuable model for studying different aspects MS pathology. CPZ feeding altered distribution expression ion channels along neuronal somata axons. However, it largely unknown whether copper chelator directly influences channels. Therefore, we assessed...
CCR2 and CCR5 receptors play a key role in the development progression of several inflammatory, cardiovascular autoimmune diseases. Therefore, dual targeting both appeals as promising strategy for treatment such complex, multifactorial disorders. Herein we report on design, synthesis biological evaluation benzo[7]annulene- [7]annulenothiophene-based selective receptor antagonists. Intermediates were designed way that diversification could be introduced at end synthesis. Starting from lead...
A stacked deep convolutional neural network (DCNN) model was generated to predict cell density maps and count cells. We treated the counting as a regression problem with preprocessing step generate maps. implemented this approach by integrating two trustworthy state-of-art architectures (U-net & VGG19). This method combines advantages from both traditional segmentation-based density-based methods. It overcomes limitations such clumping, overlapping, it can also bypass fine-tuning which...
We herein disclose the microwave-assisted synthesis of previously unreported 6-methoxy-5,6-dihydro-5-azapurines, whose purine-like scaffold is promising for drug discovery. The method simple, fast, and relies on easily accessible reagents such as trimethyl orthoformate, acetic acid, aminotriazole-derived N,N′-disubstituted formamidines. preliminary biological evaluation revealed that selected representatives synthesized 6-methoxy-5,6-dihydro-5-azapurines dose-dependently reduce viability...
The G protein-coupled receptor 17 (GPR17) is an orphan involved in inflammatory diseases. GPR17 antagonists have been proposed for the treatment of multiple sclerosis due to their potential induce remyelination. Potent, selective are required enable target validation. In present study, we describe discovery a novel class based on anthranilic acid scaffold. compounds' potencies were evaluated calcium mobilization and radioligand binding assays, structure–activity relationships analyzed....
The orthosteric ATP-binding site of the P2X receptors is poorly understood. Only a few compounds were well characterized for their receptor functional activity and subtype selectivity. This study represents first fully characterization various ATP derivatives combined with in silico studies to advance understanding SARs at binding sites leading identification 2-chloro-3-trifluoromethylbenzoyl ester as novel pan-P2X agonist several subtype-selective agonists. Furthermore, esterification both...