Synthesis of some novel pyrazolo[3,4- b]pyridine and pyrazolo[3,4- d]pyrimidine derivatives bearing 5,6-diphenyl-1,2,4-triazine moiety as potential antimicrobial agents

Abstract

The reaction of 5,6-diphenyl-3-hydrazino-1,2,4-triazine ( 1) with bis(methylthio)methylene]malononitrile ( 2) afforded 5-amino-1-(5,6-diphenyl-1,2,4-triazin-3-yl)-3-(methylthio)-1 H-pyrazole-4-carbonitrile ( 3). Compound 3 reacted with thiourea to give 3,4-diaminopyrazolo[3,4- d]pyrimidine 5, which was treated with benzoyl chloride to give pyrazolo[5,4,3- kl]pyrimido[4,3- d]pyrimidine 6. Treatment of 3 with acetic anhydride produced 3-methylthio-pyrazolo[3,4- d]pyrimidine derivative 7, which was allowed to react with hydrazine hydrate to give the corresponding hydrazino derivative 8. Heterocyclization of 8 with benzoyl chloride and sodium pyruvate afforded the polyfused heterocycles 9 and 10, respectively. Reaction of 3 with benzoylacetone yielded pyrazolo[3,4- b]pyridine 12, which was allowed to react with malononitrile and acetanilide to get heterocyclic systems 13 and 14, respectively. Interaction of 3 with cyanoacetone gave pyrazolo[3,4- b]pyridine 15, which was refluxed in formic acid to yield pyrazolo[4′,3′:5,6]pyrido[4,3- d]pyrimidine 16. Reaction of 3 with 2 afforded the triazinylpyrazole derivative 17, which was reacted with hydrazine hydrate to give dipyrazolo[1,5-a:3′,4′- d]pyrimidine 19. Furthermore, treatment of the latter compound with methyl anthranilate furnished tetraheterocyclic compound 21. Structures of the products have been determined by elemental analysis and spectral studies. All compounds have been screened for their antibacterial and antifungal activities. Compounds 9, 10, 13, 19 and 21 showed maximum activity comparable to the standard drugs with lower toxicity in the case of 9 and 10.