Monatshefte für Chemie - Chemical Monthly

, Volume 149, Issue 5, pp 969–976 | Cite as

Synthesis, pharmacological activity, and chromatographic enantioseparation of new heterocyclic compounds of the aryloxyaminopropanol type derived from 4-hydroxyphenylalkanones

  • Ružena Čižmáriková
  • Andrej Némethy
  • Ladislav Habala
  • Eva Račanská
  • Jindra Valentová
  • Katarína Hroboňová
Original Paper
  • 63 Downloads

Abstract

In the paper, a series of six pharmacologically active compounds (β-adrenolytics) derived from 4-hydroxyphenylethanone and 4-hydroxyphenylpropan-1-one are reported. The compounds incorporate pyrrolidin-1-yl and 4-methylpiperazin-1-yl substituents in the hydrophilic part of the molecule and ethoxymethyl and methoxyethoxymethyl side chains on the aromatic ring in the lipophilic moiety. They were prepared by a four-step synthesis from 4-hydroxyalkanones via chloromethyl, alkoxymethyl, and oxirane intermediates. The purity of the target compounds was checked by TLC and their structures were confirmed by the interpretation of the IR, UV, 1H NMR, and 13C NMR spectra. The pharmacological evaluation of the obtained compounds confirmed their vasodilatory and specific antiisoprenaline activities. All evaluated compounds at conc. 10−6 mol dm−3 inhibited vasoconstrictory effect of phenylephrine (8.22–33.7%) on isolated rat aorta. The ability to inhibit positive chronotropic effect of isoprenaline was observed on isolated spontaneously beating rat’s atria after pre-treatment with the evaluated compounds at conc. 10−7 and 10−6 mol dm−3. The calculated pA2 values of specific antagonistic effect against isoprenaline, related to their apparent β-adrenolytic activity, ranged between 6.54 and 7.57. The value for the standard compound carvedilol was 8.15 ± 0.22. The majority of the evaluated compounds at conc. 10−6–10−7 mol dm−3 also showed negative chronotropic effect on the basic heart rate of atria. Enantioseparation of the prepared compounds was performed by chiral HPLC on an amylose tris(3,5-dimethylphenylcarbamate) column (Chiralpak AD) and a native teicoplanin column (Chirobiotic T). The chromatographic characteristics as retention, separation, and resolution factors were reported.

Graphical abstract

Keywords

Aryloxyaminopropanols Vasodilatory Antiisoprenaline Beta-adrenolytic Chirality Drug research 

Notes

Acknowledgements

This publication utilizes research results of the CEBV project, ITMS: 26240120034. This work was supported by the Slovak Research and Development Agency under the contract no. APVV-0516-12; Vedecká Grantová Agentúra MŠVVaŠ SR a SAV (VEGA 1/0346/16).

Supplementary material

706_2018_2185_MOESM1_ESM.pdf (929 kb)
Supplementary material 1 (PDF 928 kb)

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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Chemical Theory of Drugs, Faculty of PharmacyComenius University in BratislavaBratislavaSlovak Republic
  2. 2.Department of Pharmacology and Toxicology, Faculty of PharmacyComenius University in BratislavaBratislavaSlovak Republic
  3. 3.Faculty of Chemical and Food Technology, Institute of Analytical ChemistrySlovak University of Technology in BratislavaBratislavaSlovak Republic

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