Preparation OF Some Nalidixic Acid Hydrazides Of Potential Antidepressant Activity

This thesis begins with an introduction displaying a summarized information about depression and lines of its treatment including the synthetic compounds that have been used in its treatment. Also, displaying a detailed study about MAOIs as an important group in treatment of depression. A survey of the most important and documented chemical groups that having antidepressant activity was included.The present investigation is concerned with the synthesis of nalidixic acid hydrazide in addition to 1, 3, 4-oxadiazol derivatives as an example of the cyclized hydrazides and preparation of 6-bromo nalidixic acid hydrazides.The key intermediate, 3-nalidixic acid hydrazide 3 was prepared by the reaction between the methyl ester of nalidixic acid 2 with hydrazine hydrate. The resulting hydrazide was converted into N-formylidine 4, N-alkyl dines 5-8 and N-aryl dines 9-23 by reaction with the respective aldehydes and ketones. 3-(5-Amino-1, 3, 4-oxadiazole) 26 was prepared by the reaction of the hydrazide 3 with cyanogens bromide in alkaline medium. The hydrazide 3 was converted into the thiosemicarbazide intermediates 24 and 25 by its reaction with ethyl and phenyl isothiocyanate followed by cyclization into 3-(5-substituted amino-1, 3, 4-oxadiazole) derivatives 27 and 28 in presence of iodine / sodium hydroxide.6-Bromonalidixic acid 31 was synthesized by the reaction of the methyl ester 2 with bromine (3 equivalent) resulting in the hydrolysis of ester and bromination at position 6. the 6-bromonalidixic acid 31 was converted into the corresponding methyl ester 32 by its reaction with ethylchloroformate at 0-5 oC affording the corresponding unisolated mixed anhydride that by its treatment with methanol gives the ester 32. the hydrazide 33 was prepared by the reaction of the ester 32 with hydrazine hydrate, which was converted into the hydrazones 34-39.Different trails were carried out for the synthesis of 6-bromonalidixic acid, affording two unexpected compounds; 3-bromo-1-ethyl-1, 4-dihydro-7-methyl-4-oxo-1, 8-naphthyridine 29 and 3, 6-dibromol-ethyl-1, 4-dihydro-7-methyl-4-oxo-1, 8-naphthyridine 30.