A5000281926- Mast cells and histamine
- Receptor Mechanisms and Signaling
- Polyamine Metabolism and Applications
- Chemical Synthesis and Analysis
- Phenothiazines and Benzothiazines Synthesis and Activities
- Synthesis and Characterization of Heterocyclic Compounds
- Metal complexes synthesis and properties
- Click Chemistry and Applications
- Synthesis and biological activity
- Chemical Reactions and Isotopes
- Chemotherapy-induced cardiotoxicity and mitigation
- Asthma and respiratory diseases
- Computational Drug Discovery Methods
- Olfactory and Sensory Function Studies
- Circadian rhythm and melatonin
- Heart Failure Treatment and Management
- Crystallization and Solubility Studies
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Cancer-related cognitive impairment studies
- X-ray Diffraction in Crystallography
- Synthesis and Catalytic Reactions
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Pancreatic function and diabetes
- Neuropeptides and Animal Physiology
- Cholinesterase and Neurodegenerative Diseases
Medical University of Lodz
2012-2024
University of Opole
2023
H₃ receptors present on histaminergic and non-histaminergic neurons, act as autoreceptors or heteroreceptors controlling neurotransmitter release synthesis. Previous, studies have found that the compound N-methyl-N-3-phenylalkyl-2-[2-(4-n-propylpiperazin-1-yl)-1,3-thiazol-5-yl]ethan-1-amine (ADS-531, 2c) exhibits high in vitro potency toward guinea pig jejunal receptors, with pA₂ = 8.27. To optimize structure of lead ADS-531, a series 5-substituted-2-thiazol-4-n-propylpiperazines 3 were...
This study examines the properties of a novel series 4-oxypiperidines designed and synthesized as histamine H3R antagonists/inverse agonists based on structural modification two lead compounds, viz., ADS003 ADS009. The products are intended to maintain high affinity for while simultaneously inhibiting AChE or/and BuChE enzymes. Selected compounds were subjected hH3R radioligand displacement gpH3R functional assays. Some showed nanomolar affinity. most promising compound in naphthalene was...
Abstract Aims In recent years, survival in patients with breast cancer has increased. Despite the improvement outcomes of those patients, risk treatment‐related cardiotoxicity remains high, and its presence been associated a higher treatment termination thus lower therapeutic efficacy. Prior trials demonstrated that preventive initiation heart failure drugs, including renin–angiotensin–aldosterone inhibitors, might reduce cardiotoxicity. However, to date, no study investigated efficacy...
This study examines the properties of novel guanidines, designed and synthesized as histamine H3R antagonists/inverse agonists with additional pharmacological targets. We evaluated their potential against two targets viz., inhibition MDA-MB-231, MCF-7 breast cancer cells viability AChE/BuChE. ADS10310 showed micromolar cytotoxicity cells, combined nanomolar affinity at hH3R, may represent a promising target for development an alternative method therapy. Some newly compounds moderate BuChE in...
Investigating novel, biologically-active coordination compounds that may be useful in the design of breast anticancer, antifungal, and antimicrobial agents is still main challenge for chemists. In order to get closer solving this problem, three new copper containing thiazole-based derivatives were synthesized. The structures synthesized their physicochemical characterization evaluated based on elemental analysis, 1H l3C nuclear magnetic resonance (NMR), flame atomic absorption spectroscopy...
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...
Series of 1-[2-thiazol-4-yl-(2-aminoethyl)]- and 1-[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propylpiperazine derivatives have been prepared in vitro tested as H3-receptor antagonists (the electrically evoked contraction the guinea-pig jejunum). It appeared that by comparison homologous pairs, 1-[2-thiazol-5-yl-(2-aminoethyl)]-4-n-propylpiperazines (3a,b 4a-d) much higher potency than their analogous 1-[2-thiazol-4-yl-(2-aminoethyl)]-4-n-propylpiperazines (2a-k). Based on obtained results, we...
Abstract Novel, potent non‐imidazole histamine H 3 receptor antagonists were prepared. Detailed structure–activity studies revealed that N ‐(4‐trifluoromethylbenzyl)‐ ‐[4‐(7‐phenoxyheptylpiperazin‐1‐yl)butyl]guanidine (pA 2 = 8.49 ± 0.05), 1h , and ‐(4‐nitrobenzyl)‐ 8.43 1l exhibit high affinity for the receptor. The most in this series, 1e also vitro tested as 1 antagonists, showing weak ‐antagonistic activity with pA 6.70 0.09, 6.46 6.65 0.11, respectively.
The prominent members of 1-{4-[4-(substituted)piperazin-1-yl]butyl}guanidines as histamine H<sub>3</sub>receptor antagonists.
Aims: Our research aimed to evaluate how the rigidification of characteristic 3-aminopropyloxy linker by incorporating it into 1,5-benzoxazepines affects potency histamine H3 receptor (H3R) antagonists/inverse agonists. This constitutes a starting point for full characterization pharmacological properties this group compounds. Materials & methods: Several 1,5-benzoxazepine derivatives were synthesized and pharmacologically tested as potential H3R antagonist/inverse In addition, effect on...
Autism spectrum disorder is a complex neurodevelopmental disorder. The available medical treatment options for autism are very limited. While the etiology and pathophysiology of still not fully understood, recent studies have suggested that wide alterations in GABAergic, glutamatergic, cholinergic, serotonergic systems play key role its development progression. Histamine neurotransmission known to interactions with other neurotransmitters fit perfectly into this disease. Multitarget-directed...
In this study, we selected 12 guanidine derivatives from the previously described ligand library and determined their affinity at histamine H
Antagonists to the H3 receptor are considered be potential drugs for treatment of Alzheimer's disease, attention deficit-hyperactive disorder, memory and learning deficits, epilepsy. The initial development potent antagonists focused on extensive modification natural ligand histamine. However, it has appeared that imidazole-containing ligands associated with inhibition cytochrome P450 enzymes, caused by imidazole nitrogen complexation heme iron in active site enzyme. For these reasons,...