Facile heterocyclic synthesis and antimicrobial activity of polysubstituted and condensed pyrazolopyranopyrimidine and pyrazolopyranotriazine derivatives

Abstract

Reaction of 6-amino-3-methyl-4-(substituted phenyl)-1,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile (1) with triethylorthoformate followed by treatment with hydrazine hydrate, formic acid, acetic acid, phenylisocyanate, ammonium thiocyanate and formamide afforded the corresponding pyranopyrimidine derivatives 2-6. Cyclocondensation of 1 with cyclohexanone afforded pyrazolopyranoquinoline 7. One-pot process of diazotation and de-diazochlorination of 1 afforded pyrazolopyranotriazine derivative 8, which upon treatment with secondary amines afforded 9 and 10a-c. Condensation of 2 with aromatic aldehyde gave the corresponding Schiff bases 11a,b, the oxidative cyclization of the hydrazone with appropriate oxidant afforded 11-(4 -fluorophenyl))-2-(4-substituted phenyl)-10-methyl-8,11-dihydropyrazolo-[4',3':5,6]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidines (12a,b). Structures of the synthesized compounds were confirmed by spectral data and elemental analysis. All synthesized compounds were evaluated for antibacterial and antifungal activities compared to norfloxacin and fluconazole as standard drugs. Compounds 9, 10c, 12a and 15 were found to be the most potent antibacterial agents, with activity equal to that of norfloxacin. On the other hand, compound 5 exhibited higher antifungal activity compared to fluconazole.Keywords: pyrazolopyranopyrimidine, pyrazolopyranotriazine, pyrazolopyranoquinoline, antimicrobial activity Antibiotic resistance, which results from inappropriate and irrational use of antimicrobial medicines, provides favorable conditions for resistant bacteria to emerge. This resistance of pathogenic bacteria towards available antibiotics is rapidly becoming a major worldwide problem. Hence, the design of new compounds to deal with resistant bacteria has become one of the most important goals of antibacterial research today.

A Recent Update: Antimicrobial Agents Containing Pyrazole Nucleus

“…Polysubstituted and condensed pyrazolopyranopyrimidine and pyrazolopyranotriazine were developed by Hafez et al and were subsequently found to exhibit activity against certain microbial strains [56]. Compound (31) was the most active antifungal agent.…”

“…3]. Meanwhile, compound (32) exhibited excellent activity against bacteria which was higher or equal to MIC of norfloxacin [56]. Synthesis and antimicrobial screening of acetyl sulfonamide pyrazoles, substituted 4,5-dihydropyrazole-1carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives were presented by Hamada and Abdo [57].…”

Synthesis, characterization and antibacterial activity of novel heterocycle, coumacine, and two of its derivatives

“…The type of heteroatom and the ring size along with the substituent groups on the lead structure are the principal determinants of heterocycle’s physicochemical properties (Martins et al, 2015). Although there is a massive number of pharmacologically active heterocyclic compounds acting as antitumor (Chen et al, 2014, Sadhasivam et al, 2015, Abdel-Aziem, 2017), anti-fungal (Cao et al, 2014, Chitra et al, 2017, Zhao et al, 2017), anti-viral (Zhang et al, 2014, Da Costa et al, 2017, Asif, 2017), anti-inflammatory (Khan et al, 2012, Malik, 2016, Gomha et al, 2017) and anticonvulsant (Zayed, 2014, Shakya et al, 2016, Saravanan et al, 2017), an increasing number of heterocycles have shown a potent antibacterial effect (Azab et al, 2013, Hafez et al, 2015, Chand et al, 2017).…”

Microwave-Assisted Synthesis and Cytotoxicity Evaluation of Some Novel Pyrazole Containing Imidiazole, Pyrazole, Oxazole, Thiadiazole and Benzochromene derivatives

“…Therefore, by considering all of the above biological importance of pyrazole derivatives, and in continuation of our ongoing work [31][32][33][34]. We can say that pyrazole ring has been used for prospective development of new drug against cancer cell, so we designed and synthesized a series of novel pyrazole derivatives bearing imidiazole, pyrazole, oxazole, thiadiazole, benzochromene ring under microwave irradiation in the hope of obtaining novel antiproliferative agents.…”