Targeted synthesis of 1,4-dihydro-4-oxopyri¬midine derivatives with actoprotective activity

Research for substances possessing actoprotective properties was carried out for 4-oxopyrimidine derivatives with various mechanism of biological action. First of all, this group of compounds effects on the central nervous system, exhibits antioxidant and antihypoxic activity and improves metabolic processes.

Based on the "structure-activity" approach and molecular diagrams predicted structures, molecular docking was carried out among the most promising 1,4-dihydro-4-oxopyrimidine derivatives.

In order to increase an actoprotective activity, the variation of acetyl, carboxyl and ester radicals was realized, that let to substantiate the synthesis of 1,4-dihydro-4-oxopyrimidine derivatives. Synthesis of N-substituted 1,4-dihydro-4-oxopyrimidine derivatives was performed with a modified method of cyclocondensation of N-acetyl-β-ketoamides with aromatic amines under acid catalysis. Modification of the synthesis is based on an addition to the reaction a small amounts of DMF, which let not only to increase the yield of the desired product, but also to synthesize previously inaccessible 4-oxopyrimidine derivatives.

The primary pharmacological screening compounds obtained was revealed the most active structures with pronounced actoprotective action.

As a result, 2,6-diethyl-substituted 1,4-dihydro-4-oxopyrimidine derivatives with oxygenated substituent at N-aryl fragment as "compounds-leaders" were obtained and showed a high actoprotective activity.