SYNTHESIS AND ANTI-INFLAMMATORY ACTIVITY EVALUATION OF RHODANINE DERIVATIVES WITH 2-(2,6-DICHLOROPHENYLAMINO)-PHENYLACETAMIDE FRAGMENT IN MOLECULES

The aim of work. Synthesize the new 5-ylidenerhodanine derivatives with diclofenac fragment in position 3 based on the heterocyclization reaction and Knoevenagel condensation for screening their anti-inflammatory activity. Materials and Methods. Organic synthesis, NMR spectroscopy, elemental analysis, pharmacological screening, SAR-analysis. Results and Discussion. The interaction of 2-(2,6-dichlorophenylamino)phenylacetic acid hydrazide and thiocarbonyl-bis-thioglycolic acid in ethanol medium resulted in rhodanine derivative with fragment of anti-inflammatory drug «Diclofenac» in position 3. Considering the presence of an active methylene group in position 5 the further chemical modification of synthesized rhodanine was performed via Knoevenagel condensation with various aromatic aldehydes, isatin or cinnamic aldehyde derivatives have yielded a series of 5-arylidene- and 5-isatin(3-phenylpropene)ylidene derivatives for pharmacological screening on antiexudative action. The structure of obtained compounds was confirmed by NMR spectroscopy and elemental analysis. Conclusions. The results of anti-inflammatory activity investigation of synthesized compounds allowed us to identify three highly active derivatives which was appropriate to the reference nonsteroidal inflammatory drug «Diclofenac Sodium» by indicator of inhibition of inflammatory reaction (42,4-45,3%)

SYNTHESIS AND PRIMARY SCREENING OF ANTI-INFLAMMATORY ACTIVITY OF 1,4,5,6-TETRAHYDROPYRIMIDINE-2-CARBOXAMIDES

The aim of the work. Development of methods for obtaining new morpholin-4-yl-2-thioxoacetamides and investigate their reaction with 1,3-diaminopropane; synthesis of new 1,4,5,6-tetrahydropyrimidine-2-carboxamides and primary screening of their anti-inflammatory properties. Materials and Methods. Organic synthesis, NMR spectroscopy, elemental analysis, pharmacological screening. Results and Discussion. By the reaction of chloroacetamides with sulfur and morpholine a series of 2-morpholin-4-yl-2-thioxoacetamides were synthesized. They were investigated in the reaction with 1,3-diaminopropane. As a result, the series of new 1,4,5,6-tetrahydropyrimidine-2-carboxamides were prepared. The anti-inflammatory activity of some synthesized compounds has been investigated. Conclusions. The method of synthesis of 1,4,5,6-tetrahydropyrimidine-2-carboxamides was developed. The results of anti-inflammatory activity investigation of synthesized compounds allowed us to identify highly active derivatives which was appropriate to the reference non-steroidal antiinflammatory drug “Diclofenac Sodium” by indicator of inhibition of inflammatory reaction (37.5–46.7 %)