Synthesis of new pyrimidine derivatives with evaluation of their anti-inflammatory and analgesic activities.

5-Formyl-6-aminopyrimidine-2,4-(1H, 3H)-dione (2) has been previously prepared fromcompound 1. Cyclocondensation reaction of compound 2 with cyanoacetamide gave substituted pyridopyrimidine 3. Also, compound 2 was condensed with p-amino acetophenone and hydrazine derivatives to give 5-([(4-acetylphenyl)imino]methyl)-6-aminopyrimidine (4) and 5-substituted carboaldehyde-6-amino pyrimidine derivatives (5a-d), respectively. Moreover, cyclocondensation reaction of compound 2 with thiosemcarbazide and semicarbazide hydrochloride gave 5-(5-thioxo or oxo-triazol-3-yl)-6-amino pyrimidine (6) and (7), respectively. Cyclocondensation reaction of compound 2 with thiourea and ethyl acetoacetate led to the formation of substituted ethyl bipyrimidine-5-carboxylate 8. Also, compound 2 was reacted with acetoacetic acid hydrazide and 2-cyanoacetohydrazide to give 5-(acetylpyrazol-6-aminopyrimidine 9 and 3-(6-aminopyrimidine-5-yl) pyrazole-4-carboxamide 10, respectively. Furthermore, compound 1 was diazotized to afford the diazonium salt 11. Its coupling with ethyl acetoacetate, ethyl cyanoacetate, acetylacetone, malononitrile, cyanoacetamide, diethylmalonate, in sodium acetate buffered solution afforded substituted hydrazonopyrimidines: ethylhydrazono-3-oxobutanoate 12, ethylhydrazono-3-oxopropanoate 13, pentane-2,3,4-trione hydrazone 14, cyanohydrazonoacetamide 15, diazenyl malonamide 16 and diethylhydrazonomalonate 17, respectively. Moreover, substituted pyrazolediazenylpyrimidine derivatives 18a,b, 19a,b, 20, 21a-c, 22 were synthesized by the cyclization of substituted hydrazonopyrimidines 12, 17, 15, 14 and 13, respectively. The analgesic and anti-inflammatory activities of some of the synthesized compounds were evaluated. Compounds C18a, C20, C21b and C22 showed the most significant analgesic effects among synthesized moieties. All tested compounds, nonetheless, C18b showed significant anti-inflammatory effect in carrageenan induced paw edema model.