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Synthesis and preliminary evaluation of pharmacological properties of some piperazine derivatives of xanthone.
- Source :
-
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2013 Jan 15; Vol. 21 (2), pp. 514-22. Date of Electronic Publication: 2012 Nov 24. - Publication Year :
- 2013
-
Abstract
- A series of 9 piperazine derivatives of xanthone were synthesized and evaluated for cardiovascular activity. The following pharmacological experiments were conducted: the binding affinity for adrenoceptors, the influence on the normal electrocardiogram, the effect on the arterial blood pressure and prophylactic antiarrhythmic activity in adrenaline induced model of arrhythmia (rats, iv). Three compounds revealed nanomolar affinity for α(1)-adrenoceptor which was correlated with the strongest cardiovascular (antiarrhythmic and hypotensive) activity in animals' models. The most promising compound was 4-(3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride (12) which revealed antiarrhythmic activity with ED(50) value of 0.69 mg/kg in adrenaline induced arrhythmia (rats, iv). Other synthesized xanthone derivatives, that is, (R,S)-4-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride (10) and (R,S)-4-(2-acetoxy-3-(4-(2-methoxyphenyl)piperazine-1-yl)propoxy)-9H-xanthen-9-one hydrochloride (11) also acted as potential antiarrhythmics in adrenaline induced model of arrhythmia in rats after intravenous injection (ED(50) = 0.88 mg/kg and 0.89 mg/kg, respectively). These values were lower than values obtained for reference drugs such as propranolol and urapidil, but not carvedilol. Results were quite promising and suggested that in the group of xanthone derivatives new potential antiarrhythmics and hypotensives might be found.<br /> (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Anti-Arrhythmia Agents pharmacology
Anti-Arrhythmia Agents therapeutic use
Arrhythmias, Cardiac chemically induced
Arrhythmias, Cardiac drug therapy
Blood Pressure drug effects
Heart Rate drug effects
Male
Piperazine
Protein Binding
Rats
Rats, Wistar
Receptors, Adrenergic chemistry
Receptors, Adrenergic metabolism
Stereoisomerism
Xanthones pharmacology
Xanthones therapeutic use
Anti-Arrhythmia Agents chemical synthesis
Piperazines chemistry
Xanthones chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1464-3391
- Volume :
- 21
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Bioorganic & medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 23245804
- Full Text :
- https://doi.org/10.1016/j.bmc.2012.11.014