The synthesis of new phosphonopeptidomimetics and their effect on the functional cardiac output

Authors

  • E. R. Abdurakhmanova Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • N. O. Dorofeyeva National Academy of Sciences of Ukraine Bogomoletz Institute of Physiology, Ukraine
  • O. I. Lukashuk Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • O. V. Holovchenko Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine
  • V. S. Brovarets Institute of Bioorganic Chemistry and Petrochemistry of the NAS of Ukraine, Ukraine

DOI:

https://doi.org/10.24959/ophcj.16.882

Keywords:

heart, contractility, 4-phosphorylated 5-amino-1, 3-oxazoles, phosphonopeptidomimetics, amino alcohols

Abstract

The article presents the synthesis of new phosphorylated peptidomimetics, and the biological activity of the compounds synthesized has been assessed for the fi rst time on the experimental animals – male rats. On the basis of a diethyl ester of 1-benzoylamino-2,2,2-trihloroethylphosphonic acids a novel derivative of 1,3-oxazol-4-phosphonic acid diethyl ester containing the residue of methylaminoethan-1-ol in position 5 of the oxazole ring has been synthesized. The optimal conditions for cleavage of the 1,3-oxazole ring in the acidic medium with formation of phosphorylated peptidomimetics have been found. Thus, when treating it with 85 % aqueous trifl uoroacetic acid a diethyl ester of {benzoylamino[(2-ydroxyethyl)carbamoyl]methyl} phosphonic acid has been obtained, and  the action of hydrogen chloride under anhydrous conditions gives a diethyl ester of {benzoylamino[(2-chloroethyl) carbamoyl]methyl} phosphonic acid. The method developed is very convenient and preparative because reactions proceed in mild conditions without formation of undesirable by-products. Moreover, peptidomimetics are isolated with high yields, and their isolation does not require chromatography. Monitoring of different functional parameters of cardiac hemodynamics was performed in rats in vivo using a microcatheter and the Millar Pressure-Volume System. The study of the effect of the compounds obtained on the cardiac output has shown that their intraperitoneal introduction results in the heart rate decrease and stimulation of the contractile activity of the myocardium.

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Published

2016-03-04

How to Cite

(1)
Abdurakhmanova, E. R.; Dorofeyeva, N. O.; Lukashuk, O. I.; Holovchenko, O. V.; Brovarets, V. S. The Synthesis of New Phosphonopeptidomimetics and Their Effect on the Functional Cardiac Output. J. Org. Pharm. Chem. 2016, 14, 74-77.

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Section

Original Researches