The synthesis and study of vasoactive properties of new 4-functionalized 1,3-oxazoles containing the N-methyl-D-glucamine fragment in position 5

I. N. Iakovenko, E. R. Abdurakhmanova, O. V. Holovchenko, V. V. Zhirnov, V. S. Brovarets

Abstract


The analysis of literature data shows the prospects of searching drugs with different biological activity among 1,3-oxazoles.

Aim. To develop preparative methods of the synthesis of new 4-fuctionalized 1,3-oxazoles containing the N-methyl-D-glucamine fragment in position 5 and to study their physical, chemical and biological properties.

Results and discussion. It has been found that 1,3-oxazoles reveal the vasodilatative and vasoconstrictive effect on the tonic activity of the vessels preactivated with phenylephrine depending on the concentration and the chemical structure of the compounds. The article describes the vasodilatative and vasoconstrictive efficacy of new 1,3-oxazoles compared to the known adrenolytic drug – amiodarone, and the inhibitor of potassium channels – 4-aminopyridine (pimadin).

Experimental part. A number of new 4-fuctionalized 1,3-oxazoles containing the N-methyl-D-glucamine fragment in position 5 was synthesized. Their biological activity was assessed under the action of selective agonists of 1-adrenoreceptors (phenylephrine), 5HT2A-receptor (serotonin) on the isolated segments of the rat’s aorta previously constricted or by blocking potassium channels with the high potassium Krebs solution.

Conclusions. It has been found that in the case of the serotonin constricted isolated aortic segments only the vasoconstriction is observed in contrast of the vessel activated with phenylephrine. If the constriction of the aortic segments is carried out with a high potassium solution, there is no vasotonic activity of 1,3-oxazole derivatives. The data obtained indicate the possible molecular mechanism of their biological activity with the participation of vascular adrenergic receptors and potassium channels, their inhibition may lead to vasodilatation at the comparatively high concentration of the compounds or vasoconstriction at the comparatively low concentration of oxazoles, respectively. 


Keywords


blood vessels; biologically active substances; N-methyl-D-glucamine; 4-functionalized 1,3-oxazoles

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DOI: https://doi.org/10.24959/ophcj.17.921

Abbreviated key title: Ž. org. farm. hìm.

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