Synthesis of 2-{3-[4-(4-fluorophenyl)-1-piperazinyl]-2-hydroxy-propoxy}-phenylcarbamic acid alkylesters and in vitro evaluation of their ß-antiadrenergic and vasodilatative activities

Overview

In effort to obtain effective compounds able to favourably influence pathologically changed cardiovascular functions, such as hypertension and ischemic cardiac disease, a new series of aryloxyaminopropanols were synthesized. Four of the compounds, which differ in the alkyl substitution of phenylcarbamate (methyl, ethyl, propyl, butyl), were chosen for basic in vitro pharmacological analyses. In experiments on the isolated spontaneously beating guinea pig atria all compounds at conc. of 1.0.10⁻⁶ mol.l⁻¹ decreased the basic heart rate (7.6–13.6%) and inhibited the positive chronotropic effect of isoprenaline (pA2 = 6.28–6.81). The compounds manifest only a slight relaxation effect on KCl pre-contracted aortal strips of rats (not until conc. of 1.0.10⁻⁵ mol.l⁻¹). The compounds with propyl and butyl substitution appear more effective than the methyl and ethyl derivatives.

Key words:
aryloxyaminopropanols –⁠ β-antiadrenergic –⁠ isolated atria –⁠ isolated aorta