PREPARATION OF SOME NALIDIXIC ACID HYDRAZIDES OF POTENTIAL ANTIDEPRESSANT ACTIVITY

Abstract

This thesis begins with an introduction displaying a summarized information about depressioi1 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 I ,3,4-oxadiazol derivatives as an example of the cyclized hydrazides and preparation of 6-bromo nalidixic acid hydrazides. The key intennediate, 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-fonnylidine 4, N­ alkylidines 5-8 and N-arylidines 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 cyanogen bromide in alkaline medium. The hydrazide 3 was converted into the thiosemicarbaiide intennediates 24 and 25 by its reaction with ethyl and phenyl isothiocyanate followed by cyclization into 3-(5-substituted amino-!,3,4-oxadiazo\e) derivatives 27 and 28 in presence of iodine I 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.