DOI: https://doi.org/10.24959/ophcj.20.193867

The study of the neurotropic activity of the pyrrolopyrimidin-4-ones rearrangement products under the action of phosphorus oxychloride

Ekaterina V. Zaliznaya, Svetlana A. Varenichenko, Oleg K. Farat, Victor I. Markov

Abstract


Aim. To synthesize the annelated 4-aminopyridines and study the biological activity of one of products.

Results and discussion. In the laboratory of the Research Institute of Biomedical Problems of the Dnipropetrovsk Medical Academy the studies of the effect of 2,3,3-trimethyl-2,3,5,6,7,8-hexahydro-1H-pyrrolo[3,4-b]quinolin-9-amine on the neuroactivity in the “open field” model have been conducted. According to the results of the experiment it has been found that in two hours after the administration of the oil solution of the compound the indices of the motor activity of mice are significantly reduced.

Experimental part. 2,3,3-Trimethyl-2,3,5,6,7,8-hexahydro-1H-pyrrolo[3,4-b]quinolin-9-amine and 2,3,6,7,7-pentamethyl-6,7-dihydro-5H-pyrrolo[3,4-b]pyridin-4-amine were obtained by the rearrangement of the corresponding pyrrolopyrimidin-4-ones under the action of the excess of phosphorus oxychloride in toluene. The initial pyrrolopyrimidin-4-ones were synthesized by the condensation of 4-amino-1,2,2-trimethyl-2,5-dihydro-1H-pyrrole-3-carbonitrile with ketones. The structure of all compounds obtained was confirmed by 1H NMR-spectroscopy, mass spectrometry and elemental analysis.

Conclusions. The neurotropic activity has been detected for the oil solution of 2,3,3-trimethyl-2,3,5,6,7,8-hexahydro-1H-pyrrolo[3,4-b]quinolin-9-amine on the “open field” model. It has been found that the aqueous solution of this compound does not exhibit the neurotropic activity regardless of the administered dose. Taking into account the presence of the neurotropic activity further research in this field is a promising way to search novel bioactive molecules among 4-aminopyridine derivatives, which are structural analogs of the drug Tacrine.

 

Received: 26.12.2019
Revised: 20.01.2020
Accepted: 27.02.2020


Keywords


rearrangement; pyrrolopyrimidin-4-ones; aminohydroacridines; neurotropic activity; Tacrine

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Abbreviated key title: J. Org. Pharm. Chem.

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