A5031923976- Radiopharmaceutical Chemistry and Applications
- Boron Compounds in Chemistry
- Boron and Carbon Nanomaterials Research
- Nuclear Physics and Applications
- Synthetic Organic Chemistry Methods
- Medical Imaging Techniques and Applications
- Asymmetric Hydrogenation and Catalysis
- Quinazolinone synthesis and applications
- Synthesis and biological activity
- Receptor Mechanisms and Signaling
- Chronic Lymphocytic Leukemia Research
- Immune Response and Inflammation
- Pharmaceutical Economics and Policy
- Chemokine receptors and signaling
- Antimicrobial Peptides and Activities
- Toxin Mechanisms and Immunotoxins
- Crystallization and Solubility Studies
- Melanoma and MAPK Pathways
- Lymphoma Diagnosis and Treatment
- Neurobiology and Insect Physiology Research
- Pharmaceutical Practices and Patient Outcomes
- Chemical Synthesis and Analysis
- Crystallography and molecular interactions
- Research on Leishmaniasis Studies
- Natural product bioactivities and synthesis
Bayer (Germany)
2018-2024
Medizinische Hochschule Hannover
2007
University of Göttingen
1998-2003
Technical University of Denmark
2001
Interleukin-1 receptor-associated kinase 4 (IRAK4) plays a critical role in innate inflammatory processes. Here, we describe the discovery of two clinical candidate IRAK4 inhibitors, BAY1834845 (zabedosertib) and BAY1830839, starting from high-throughput screening hit derived Bayer's compound library. By exploiting binding site features distinct to using an in-house docking model, liabilities original could surprisingly be overcome confer both candidates with unique combination good potency...
Transient receptor potential ankyrin 1 (TRPA1) is a voltage-dependent, ligand-gated ion channel, and activation thereof linked to variety of painful conditions. Preclinical studies have demonstrated the role TRPA1 receptors in broad range animal models acute, inflammatory, neuropathic pain. In addition, clinical study using antagonist GRC-17536 (Glenmark Pharmaceuticals) efficacy subgroup patients with diabetic neuropathy. Consequently, there an increasing interest inhibitors as analgesics....
The synthesis of the novel unprotected carboranyl C-glycosides 2 and 20-24 starting from ethynyl 1, 5-8, 10, 13 is described. new compounds are highly water-soluble display only a very low cytotoxicity, which makes them promising candidates for use in boron neutron capture therapy treatment cancer.
A short synthesis of novel carboranyl glycosides such as the one on right for use in treatment cancer by boron neutron-capture therapy is described.
The synthesis and biological evaluation of two ortho-carborane derivatives which contain a 5,6,7-trimethoxyindole (TMI) unit for use in boron neutron capture therapy is described. TMI moiety known to be the DNA-binding part highly potent anticancer agent duocarmycin A. were prepared from amino alkynes bound protected carboxylic acid. Addition decaborane(14) alkyne triple bond with subsequent removal tert-butoxycarbonyl (Boc) benzyl protecting groups gave desired product. Boron uptake into...
The synthesis and biological evaluation of two ortho-carborane derivatives which contain a 5,6,7-trimethoxyindole (TMI) unit for use in boron neutron capture therapy is described. TMI moiety known to be the DNA-binding part highly potent anticancer agent duocarmycin A. were prepared from amino alkynes bound protected carboxylic acid. Addition decaborane(14) alkyne triple bond with subsequent removal tert-butoxycarbonyl (Boc) benzyl protecting groups gave desired product. Boron uptake into...
The presence and growth of endometrial tissue outside the uterine cavity in endometriosis patients are primarily driven by hormone-dependent inflammatory processes-the latter being frequently associated with severe, acute, chronic pelvic pain. EP4 subtype prostaglandin E2 (PGE2) receptors (EP4-R) is a particularly promising anti-inflammatory antinociceptive target as both this receptor pathways forming PGE2 highly expressed endometriotic lesions. High-throughput screening resulted...
The synthesis of new ortho-carboranyl lactosides 8, 17, 19 and glucosides 22 23 for the use in boron neutron capture therapy is reported. Carboranyl 17 as well contain a fluorine atom to allow noninvasive determination these compounds tumor cells by 19F-NMR spectroscopy. In cloning efficiency tests on human bronchial carcinoma carboranyl displayed almost no cytotoxicity. Thus, considerably cytotoxic alcohol 11 detoxified when linked sugar moiety such glucoside 22.
Boron neutron capture therapy is a special type of radiotherapy for the treatment cancer by using boron compounds. Problems often arise from low water solubility these compounds, their unselective uptake into cells, and toxicity. Here we describe novel water-soluble ortho-carboranyl bisglycosides 7 10 containing either lactose or glucose mixed 1 28 glucose, mannose, galactose. The carboranyl show almost no toxicity toward bronchial carcinoma cells line A549 up to concentration 0.50 mM. As...
A novel method for the synthesis of bicyclic amines has been developed. Cyclisation 1,6-dienes by intramolecular hydrovinylation in presence catalytic amounts allylpalladium chloride dimer afforded one step. Added phosphines, silver salts, as well nature N-protecting group influenced yield and selectivity reactions. Most strikingly, allowed preparation diastereomerically pure e.g. hexahydroindoles 2a–2d.
Abstract Activated B-cell-like diffuse large B-cell lymphoma (ABC-DLBCL) is frequently characterized by aberrant activation of both B-Cell Receptor (BCR) & TLR/MYD88 signaling pathways. Constitutive BCR via Bruton's tyrosine kinase (BTK) and PI3K pathways leads to downstream NF-κB AKT signaling. In addition, IRAK4 mediated the pathway further activates pro-survival Simultaneous blockade inhibition in combination with pharmacological PI3K/BCR may therefore provide a novel treatment...
The human pituitary adenylate cyclase-activating polypeptide receptor (hPAC1-R), a class B G-protein-coupled (GPCR) identified almost 30 years ago, represents an important pharmacological target in the areas of neuroscience, oncology, and immunology. Despite interest this target, only very limited number small molecule modulators have been reported for receptor. We herein describe results drug discovery program aiming identification potent selective hPAC1-R antagonist. An initial...
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at glance that was extracted from about 100 leading journals. To access of an article which published elsewhere, please select “Full Text” option. The original trackable via the “References”