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Abstract
Several 6-(substituted)-5-cyano-2-thiouracils 1a-d, were prepared by the condensation of different aldehydes with ethylcyanoacetate and thiourea through a single step reaction by conventional and microwave irradiation technique. The compounds 6-(substituted)-5-cyano-2-thiouracils 1a-d were further treated with methyl iodide in presence of potassium carbonate and N,N-dimethyl formamide, as solvent to get 1-methyl-2-methylthio-4- (substituted)-5-cyano-1,6-dihydropyrimidine-6-ones 2a-d. Methylated compounds were further treated with heterocyclic secondary amines like N-methylpiperazine, piperazine and morpholine to get 3a-d, 4a-d and 5a-d. All the synthesized compounds were screened for their antimicrobial activity and were characterized by elemental analyses, IR, ^sup 1^H NMR and mass spectral data.
Key words: Antimicrobial activity, morpholines, microwave methods, pyrimidines, piperazines,
Introduction
The medicinal value of pyrimidine derivatives is significant among various heterocycles, as they are found to possess antineoplastic,1-3 antiviral,4-6 antibiotic7 and anti-inflammatory8 including other biological activities. Further drugs containing piperazine and morpholine moiety have exhibited remarkable biological properties, viz Diethylcarbamazine as potent filaricide, Phendimetrazine as CNS stimulant, Cyclizine as antihistamine and Prazocin as antihypertensive. Some analogs of these class like 2,6-diketopiperazine derivative Razoxane is more effective in the soft tissue sarcoma and leukemia.9 It has been observed that piperazine linked with pyrimidine lead, Ritanserin as 5HT2 antagonist with anxiolytic activity,10 Buspirone is a well known drug with pyrimidine moiety linked with piperazine analog indicated in the management of anxiety disorder encompassed with or without depression.11-12 The several phenothiazines, tricyclic antipsychotic drugs are substituted with piperazine heterocycle by replacing long chain of aliphatic amine, these substitutions produced the most potent phenothiazine antipsychotic compounds. Terry et al, have evaluated pyrimidine derivatives linked to morpholine group for its VEGF-R2 inhibitor activity and showed to be effective in a mouse model of corneal neovascularization.13 The novel 4- benzylamino-2-[(4-morpholin-4- ylphenyl)amino] pyrimidine-5- carboxamide derivatives (YM-341619, AS1617612) potently inhibited STAT6 activation.14 All these observations point out that pyrimidines, piperazine and morpholine occupies distant and remarkable place in medicinal chemistry. Keeping in view of these above facts, it was thought of synthesizing some pyrimidine derivatives incorporated with piperazine and morpholine groups to explore their biological profile.
The starting material 6-(Substituted)-5- cyano-2-thiouracils 1a-d, obtained by reported procedure,15 were stirred with methyl iodide in presence of N,NDimethylformide and K2CO3 to get 1- methyl-2-methylthio-4-(substituted)-5- cyano-1,6-dihydropyrimidine-6-ones 2a-d. The formation of the 2b was confirmed by recording its 1H NMR...