A5060987539- Synthesis and Biological Evaluation
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Phosphodiesterase function and regulation
- Neurotransmitter Receptor Influence on Behavior
- Pharmacological Receptor Mechanisms and Effects
- Synthesis and Reactions of Organic Compounds
- Adenosine and Purinergic Signaling
- Neuroscience and Neuropharmacology Research
- Synthesis and biological activity
- Chemical synthesis and alkaloids
- Analytical Chemistry and Chromatography
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Reactivity of Heterocycles
- Crystallography and molecular interactions
- Cholinesterase and Neurodegenerative Diseases
- Tryptophan and brain disorders
- Metabolism, Diabetes, and Cancer
- Computational Drug Discovery Methods
- Diabetes Treatment and Management
- Innovative Microfluidic and Catalytic Techniques Innovation
- Synthesis of heterocyclic compounds
Jagiellonian University
2012-2021
Medicina
2011-2021
Universitäre Psychiatrische Dienste Bern
2019
Medical University of Lodz
2007-2017
Technical University of Denmark
2015-2017
Klinikum Ingolstadt
2017
Copernicus Memorial Hospital
1988-2016
Institute of Medicinal Plant Development
2016
Wojewódzki Szpital Specjalistyczny Nr 2
2015
Institut des Biomolécules Max Mousseron
2010
Modulators of the serotonin 5-HT6 receptor (5-HT6R) offer a promising strategy for treatment cognitive deficits that are associated with dementia and Alzheimer's disease. Herein, we report design, synthesis, characterization novel class 5-HT6R antagonists is based on 1H-pyrrolo[3,2-c]quinoline core. The most active compounds exhibited comparable binding affinity to reference compound, SB-742457, markedly improved selectivity. Lead optimization led identification...
This paper describes a rhodopsin-based model of 5-HT1A serotonin receptor. The flexibility the receptor was considered by using large number models for ligand dockings. Rearrangements heptahelical bundle were introduced, which resulted in improvement correlation between computational results and experimental data. validated automated docking conformationally restricted arylpiperazines. Specific interactions, responsible recognition arylpiperazine derivatives, identified. An ionic bond formed...
In order to target behavioral and psychological symptoms of dementia (BPSD), we used molecular modeling-assisted design obtain novel multifunctional arylsulfonamide derivatives that potently antagonize 5-HT(6/7/2A) D2 receptors, without interacting with M1 receptors hERG channels. vitro studies confirmed their antagonism 5-HT(7/2A) weak interactions key antitargets (M1R hERG) associated side effects. Marked 5-HT6 receptor affinities were also observed, notably for...
Recent breakthroughs in crystallographic studies of G protein-coupled receptors (GPCRs), together with continuous progress molecular modeling methods, have opened new perspectives for structure-based drug discovery. A crucial enhancement this area was development induced fit docking procedures that allow optimization binding pocket conformation guided by the features its active ligands. In course our research program aimed at discovery novel antipsychotic agents, attention focused on...
A set of 31 diversified 5-HT7 receptor antagonists was automatically docked to a conformational ensemble rhodopsin-based 5-HT7R models (flexible docking). It found that ergolines, aporphines, and tricyclic psychotropic agents were always in pocket formed by TMHs 4−6, besides the main ionic bond with Asp3.32, they had specific interactions Phe6.52, Phe6.51, Trp6.48, Ser5.42. The arylpiperidine, arylpiperazine, or β-carboline fragment complex ligands occupied same pocket, whereas terminal...
A series of 8-substituted derivatives 3,7-dimethyl-1-propargylxanthine (DMPX) was synthesized and investigated as A2A adenosine receptor antagonists. Different synthetic strategies for the preparation DMPX analogues were explored. recently developed procedure starting from 3-propargyl-5,6-diaminouracil proved to be method choice this type xanthine derivatives. The novel compounds in radioligand binding studies at high-affinity subtypes A1 compared with standard Structure-activity...
The most troublesome aspects of behavioral and psychological symptoms dementia (BPSD) are nowadays addressed by antidepressant, anxiolytic, antipsychotic drugs, often administered off-label. Considering their modest effectiveness in patients, the increased risk adverse events cognitive decline, there is an unmet need for well-tolerated effective therapy BPSD. We designed synthesized multifunctional ligands characterized vitro as high-affinity partial agonists D2R, antagonists 5-HT6R,...
Novel 1-(1-benzoylpiperidin-4-yl)methanamine derivatives were designed as "biased agonists" of serotonin 5-HT1A receptors. The compounds tested in signal transduction assays (ERK1/2 phosphorylation, cAMP inhibition, Ca2+ mobilization, and β-arrestin recruitment) which identified ERK1/2 phosphorylation-preferring aryloxyethyl derivatives. novel series showed high receptor affinity, >1000-fold selectivity versus noradrenergic α1, dopamine D2, 5-HT2A, histamine H1, muscarinic M1 receptors,...
Study Objectives:Obstructive sleep apnea syndrome (OSAS) is often associated with impaired glucose metabolism. Data on the effects of OSAS treatment continuous positive airway pressure (CPAP) blood and insulin resistance are conflicting. The study aimed at assessing immediate effect CPAP control measured a monitoring system (CGMS).