الفهرس 
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Abstract
A new series of bumetanide derivatives have been synthesized with the aim to explore their biological activities specially the carbonic anhydrase inhibitiory, anti-inflammatory and antimicrobial activities.
Our starting synthon bumetanide which is chemically 3-(butylamino)-4-phenoxy-5-sulfamoyl-benzoic acid (I) was esterified with methanol to obtain its methyl ester derivative II1 which underwent hydrazinolysis to afford the new acid hydrazide key intermediate III.
The newly synthesized acid hydrazide intermediate III was condensed with different aldehydes to obtain different novel hydrazones IVa-i. Furthermore, bumetanide acid hydrazide III was condensed with different aromatic acids in presence of phosphorous oxychloride (POCl3) to give new various 1,3,4-oxadiazoles Va-e, while it was condensed with ethylacetoacetate (EAA) in presence of ethanolic potassium hydroxide to give a new 3-pyrazolone derivative VI.
In addition, the acid hydrazide III was cyclized using carbon disulfide and potassium hydroxide to obtain a novel 5-mercapto-1,3,4-oxadiazole derivative VII. Moreover, the intermediate hydrazide III was cyclized with β diketones like acetylacetone or benzoylacetone to afford the new pyrazole derivatives VIIIa,b.
On the other side, the target thiosemicarbazide derivatives IXa-c were prepared via reaction of the acid hydrazide III with isothiocyanate derivatives. The prepared thiosemicarbazide derivatives IXa-c were cyclized by 2 pathways, firstly by using sodium hydroxide to afford a novel 1,2,4-triazole derivatives XIa-c and secondly via condensation with a series of phenacyl bromides to afford a new thiazole derivatives Xa-i.
The antimicrobial activity of the newly synthesized compounds I, II, III, IVa-i and Va-e was carried out adopting microplate broth assay against fungi like Aspergillus fumigatus and Candida albicans using amphotericin B as a reference drug, G+ve bacteria as Staphylococcus aureus and G-ve bacteria represented by Pseudomonas aeruginosa and Escherichia coli, using sulfamethoxazole as reference drug. Surprisingly, the results showed that compound IVi demoed an excellent antibacterial activity better than that of the reference sulfamethoxazole against Escherichia coli, while compounds IVc, IVe and IVg showed good activity against all tested bacterial strains equals to sulfamethoxazole. Moreover, compounds IVg and Vd exert an antibacterial activity equals to that of sulfamethoxazole especially against Pseudomonas aeruginosa, while compounds IVa, IVb, IVc, IVf, IVg and IVh exhibit similar activity to sulfamethoxazole against Escherichia coli. Unfortunately, all the series showed no activity against fungi.