Search

2-(5-oxothiazolidinone)-cyanoacetamido derivative 3 was prepared in two steps by reaction of 2-(2-cyano-acetylamino)-4,5,6,7-tetrahydro-benzo[b]thiophene-3-carboxamide (1) with phenyl isothiocyanate and chloroacetyl chloride, which diazocoupled with p-tolyldiazonium chloride in pyridine to afford the corresponding hydrazono derivative 4. Also, condensation of 3 with p-anisaldehyde gave the corresponding arylidine derivative 5. Treatment of 2 with dimethyl sulfate afforded the ketene N,S-acetal 9 which give 5-amino pyrazole derivative 10 upon treatment with hydrazine hydrate. Compound 10 was used as key intermediate for synthesis of pyrazolo[5,1-c][1,2,4]triazine 13a, b, pyrazolo[5,1-a]pyrimidine 14-17 and pyrolo pyrazole 18 derivatives. Finally, condensation of 1 with DMF-DMA afforded the corresponding acryloamide derivative 19, which afforded the corresponding pyrazole derivative 20 upon heating with hydrazine hydrate. All new synthesized compounds were evaluated as antimicrobial agents; some of them exhibited promising activities., (Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.)

The aim of this study involves the synthesis of novel heterocyclic scaffolds containing quinoline moiety and studying their role as antimicrobial agents. 4‐hydroxy‐6‐phenyl‐2H‐pyrano[3,2‐c]quinoline‐2,5(6H))‐dione (1) was utilized as a precursor for the construction of new polyheterocyclic ring systems. It reacted with three aryl and (heteroaryl) aldehydes to furnish the corresponding arylidenes 2a‐c. The nucleophilic cyclization of compound 2 with hydrazine hydrate to give pyrazolyl quinolinone 3. Moreover, the reaction of 1 with HCHO/morpholine led to the formation of the adduct 7. The synthesized N‐(5–3‐formyl‐4‐hydroxy‐6‐phenyl‐2,5‐dioxo‐5,6‐dihydro‐2H‐pyrano [3,2‐c] quinoline (10) was utilized for the synthesis of 3‐(([aryl]amino)methylene)‐6‐phenyl‐2H‐pyrano[3,2‐c]quinoline‐2,4,5 (3H,6H)‐trione 11a‐c via its treatment with three types of amines. Treatment of 1 with POCl3/Et3N afforded the corresponding 4‐chloro derivative 20. Which upon treatment with thiourea lead to the formation of the corresponding 4‐mercapto derivative 21. The latter 21 was alkylated using ethylbromo acetate giving 22. All freshly synthesized scaffolds were elucidated by considering the data of both elemental and spectral analyses. The synthesized scaffolds were screened for antimicrobial activities also showed promising results. The p‐chlorobenzylidene pyrazolylquinolone derivative 3 has excellent antimicrobial properties against Proteus vulgaris compared to its mild activity against Staph aureus. While 4‐Chloro‐6‐phenyl‐2H‐pyrano[3,2‐c]quinoline‐2,5(6H)‐dione (20) exhibited good activates against Staph aureus surpassing the activity of reference antibiotic. Also, compounds 21 showed excellent antifungal activity against Candida albicans higher than fluconazole. [ABSTRACT FROM AUTHOR]