Синтез і дослідження вазоактивних властивостей нових фосфорильованих пептидоміметиків

• Дата: 2013
• Автори: Iakovenko, I. N., Lukashuk, O. I., Kondratyuk, K. M., Golovchenko, A. V., Zhyrnov, V. V., Brovarets, V. S.
• Формат: Стаття
• Мова: Ukrainian
• Опубліковано: National University of Pharmacy 2013
• Теми: кровоносні судини; біологічно активні речовини; вазодилататори; пептидоміметики; УДК 547.787 547.79; 57.083.3
• Онлайн доступ: https://ophcj.nuph.edu.ua/article/view/ophcj.13.753
• Назва журналу: Journal of Organic and Pharmaceutical Chemistry

The paper presents the synthesis of new phosphorylated peptidomimetics and their action on the isolated rat aorta. It has been shown that derivatives of diethyl 5-amino-2-phthalimidoalkyl-1,3-oxazol-4-ylphosphonates can be employed in the synthesis of phosphorylated peptidomimetics containing a phosphonoglycine residue. For this purpose derivatives of 1,3-oxazol-4-ylphosphonates were decomposed hydrolytically in the acidic medium. The reaction of diethyl 5-alkylamino-2-aminoalkyl-1,3-oxazol-4-ylphosphonates with unsaturated azlactones was used to obtain phosphorylated peptidomimetics with dehydroamino acid groups. The method developed is very convenient and preparative because reactions proceed in mild conditions without formation of undesirable byproducts. Peptidomimetics are isolated with high yields and their separation does not require chromatography. Biological research has revealed the vasodilating activity of new derivatives of phosphorylated peptidomimetics depending on their chemical structure when acting on the rat’s isolated aorta. The possible molecular mechanisms of this activity with participation of the plasma membrane Ca2+-channels of vascular smooth muscle cells are discussed. The data of impact of an inhibitor of voltage-dependent Ca2+-channels of L-type of nitrendipine on the vascular tone are reported. It has been found that the concentration dependences of the vasodilating activity of the diethyl esters of 5-alkylamino-2-{N-[N-benzoyl-(4-methylbenzylidene)glycyl]aminomethyl}-1,3-oxazol- 4-ylphosphonates synthesized and nitrendipine are similar. It can testify about the indirect detection of the vasodilatory effect of these compounds associated with inhibition of the calcium signal system. The study shows a direct effect of the compounds synthesized on the muscle cells of blood vessels.