A5017457843- Receptor Mechanisms and Signaling
- Mast cells and histamine
- Phenothiazines and Benzothiazines Synthesis and Activities
- Click Chemistry and Applications
- Allergic Rhinitis and Sensitization
- Dermatology and Skin Diseases
- Monoclonal and Polyclonal Antibodies Research
- Cholinesterase and Neurodegenerative Diseases
- Computational Drug Discovery Methods
- Neuroendocrine regulation and behavior
- Asthma and respiratory diseases
- Autism Spectrum Disorder Research
- Urticaria and Related Conditions
- PI3K/AKT/mTOR signaling in cancer
- Luminescence and Fluorescent Materials
Heinrich Heine University Düsseldorf
2021-2024
University of Münster
2020
Neurodegenerative diseases such as Alzheimer's disease (AD) are multifactorial with several different pathologic mechanisms. Therefore, it is assumed that multitargeted-directed ligands (MTDLs) which interact biological targets relevant to the diseases, might offer an improved therapeutic alternative than using traditional "one-target, one-molecule" approach. Herein, we describe new benzothiazole-based derivatives a privileged scaffold for histamine H3 receptor (H3R). The most affine...
Abstract Various disorders are accompanied by histamine‐independent itching, which is often resistant to the currently available therapies. Here, it reported that pharmacological activation of Slack (Kcnt1, K Na 1.1), a potassium channel highly expressed in itch‐sensitive sensory neurons, has therapeutic potential for treatment itching. Based on Slack‐activating antipsychotic drug, loxapine, series new derivatives with improved pharmacodynamic and pharmacokinetic profiles designed enables...
Autism spectrum disorder (ASD) is a complex heterogeneous neurodevelopmental characterized by social and communicative impairments, as well repetitive restricted behaviors (RRBs). With the limited effectiveness of current pharmacotherapies in treating behaviors, present study determined effects acute systemic treatment novel multi-targeting ligand ST-2223, with incorporated histamine H3 receptor (H3R) dopamine D2/D3 affinity properties, on ASD-related RRBs male Black Tan BRachyury (BTBR)...
Alzheimer's disease (AD) is a neurodegenerative disorder, for which there no effective cure. Current drugs only slow down the course of disease, and, therefore, an urgent need to find therapies that not treat, but also prevent it. Acetylcholinesterase inhibitors (AChEIs), among others, have been used years treat AD. Histamine H3 receptors (H3Rs) antagonists/inverse agonists are indicated CNS diseases. Combining AChEIs with H3R antagonism in one structure could bring beneficial therapeutic...
This article describes the discovery of novel potent muscarinic receptor antagonists identified during a search for more active histamine H3 (H3R) ligands. The idea was to replace flexible seven methylene linker with semirigid 1,4-cyclohexylene or p-phenylene substituted group previously described H3R ADS1017 and ADS1020. These simple structural modifications antagonist led emergence additional pharmacological effects, some which unexpectedly showed strong potency at receptors. paper reports...
The therapy of depression is challenging and still unsatisfactory despite the presence many antidepressant drugs on market. Consequently, there a continuous need to search for new, safer, more effective therapeutics. Previous studies have suggested potential association brain histaminergic/serotoninergic signaling antidepressant- anxiolytic-like effects. Here, we evaluated in vivo effects newly developed multiple-active ligand ST-2300. ST-2300 was from 5-HT2A/2C inverse agonist pimavanserin...
Long-chain arylpiperazine scaffold is a versatile template to design central nervous system (CNS) drugs that target serotonin and dopamine receptors. Here we describe the synthesis biological evaluation of ten new derivatives designed obtain an affinity profile at 5-HT1A, 5-HT2A, 5-HT7 receptor, D2 receptor prospective treat core symptoms autism spectrum disorder (ASD) or psychosis. Besides structural features required for receptors, compounds incorporated fragments with antioxidant...
Abstract Various disorders are accompanied by histamine-independent itching, which is often resistant to the currently available therapies. In this study, we hypothesized that pharmacological activation of Slack (Kcnt1, K Na 1.1), a potassium channel highly expressed in itch-sensitive sensory neurons, has therapeutic potential for treatment itching. Based on Slack-activating antipsychotic drug, loxapine, designed series new derivatives with improved pharmacodynamic and pharmacokinetic...