Synthesis and Pharmacological Evaluation of New 1‐[3‐(4‐Arylpiperazin‐1‐yl)‐2‐hydroxypropyl]‐pyrrolidin‐2‐one Derivatives with Anti‐arrhythmic, Hypotensive, and α‐Adrenolytic Activity

Abstract

A series of novel arylpiperazines bearing a pyrrolidin-2-one fragment was synthesized and evaluated for the binding affinity of the alpha(1)- and alpha(2)-adrenoceptors (AR) and for the antiarrhythmic and hypotensive activities of the compounds. The most potent and selective compound 1-[2-hydroxy-3-[4-[(2-hydroxyphenyl)piperazin-1-yl]propyl]pyrrolidin-2-one 8 binds with pK(i) = 6.71 for alpha(1)-AR. Derivative 8 was also the most active in the prophylactic antiarrhythmic test in adrenaline-induced arrhythmia in anaesthetized rats. Its ED(50 )value equals 1.9 mg/kg (i.v.). Compounds with substituents such as a fluorine atom 4, a methyl 5, or a hydroxyl 8 group, or two substituents such as fluorine/chlorine atoms and methoxy groups in the phenyl ring, significantly decreased the systolic and diastolic pressure in normotensive anesthetized rats at a dosages of 5-10 mg/kg (i.v.). It was found that the presence of the piperazine ring and a hydroxy group in the second position of the propyl chain are critical structural features in determining the affinity of the compounds tested.

Biological evaluation of 10-(diphenylmethylene)- 4-azatricyclo[5.2.1.02,6]dec-8-ene-3,5-dione derivatives

“…In the present study 10-(diphenylmethylene)-4-azatricyclo-[5.2.1.0 2,6 ]dec-8-ene-3,5-dione and its derivatives ( Figure 1) were tested in vitro against bacteria, yeast-like organisms and viruses.…”

“…The list of 10-(diphenylmethylene)-4-azatricyclo[5.2.1.0 2,6 ]dec-8-ene-3,5-dione and its derivatives that were studied is shown in Figure 1. Compounds used in this work were synthesized previously [20].…”

“…Numerous compounds containing the 3-amino-2-hydroxypropyl/propoxy fragment express cardiostimulant, antiarrhytmic and hypotensive activity, acting at β-or α-adrenargic receptors [1][2][3][4]. Inserting selected piperazine moieties into the oxypropanolamine side chain increases the antagonistic α 1 -adrenergic properties [5,6].…”

“…The introduction of an aryl group to the piperazine moiety shifted the activity from antibacterial [16] to antiviral, with a specific action against HIV [17][18][19]. To further define these effects, we decided to investigate derivatives, generally differently substituted 10-(diphenylmethylene)-4-azatricyclo[5.2.1.0 2,6 ]dec-8-ene-3,5-diones. Their activities against bacteria, fungi and viruses were examined.…”

Synthesis of Some Unique Carbamate Derivatives bearing 2-Furoyl-1-piperazine as Valuable Therapeutic Agents

“…The piperazine has been classified as a privileged structure and is frequently found in biologically active compounds across a number of different therapeutic areas 2 which encompass anti-microbial, anti-tubercular, anti-psychotic, anti-convulsant, anti-depressant, anti-inflammatory, cytotoxic, anti-malarial, anti-arrhythmic, antioxidant and anti-viral activities. 3,4 Abbasi et al: Synthesis of Some Unique Carbamate Derivatives ...…”