%0 Journal Article
%T Synthesis and Biological Evaluation of Some [1,2,4]Triazolo[4,3-a]quinoxaline Derivatives as Novel Anticonvulsant Agents
%A Mohamed Alswah
%A Adel Ghiaty
%A Ahmed El-Morsy
%A Kamal El-Gamal
%J ISRN Organic Chemistry
%D 2013
%R 10.1155/2013/587054
%X 2-([1,2,4]Triazolo[4,3-a]quinoxalin-4-ylthio)acetic acid hydrazide (10) was used as a precursor for the syntheses of novel quinoxaline derivatives with potential anticonvulsant properties. The newly synthesized compounds have been characterized by IR, 1H£¿NMR, and mass spectral data followed by elemental analysis. The anticonvulsant evaluation was carried out for eleven of the synthesized compounds using metrazol induced convulsions model and phenobarbitone sodium as a standard. Among this set of tested compounds, two of them (14, and 15b) showed the best anticonvulsant activities. 1. Introduction Syntheses of quinoxalines have attracted a great deal of attention in view of their potent biological and pharmacological activities including anticonvulsant [1¨C4], antibacterial [5], antifungal [6], antiviral [7], antitubercular [8], antileishmanial [9], antiamoebic [10], analgesic [11], antihistaminic [12], antineoplastic [13], hypoglycemic [14], MAO-A inhibitor [15], antiarrhythmic [16], antiatherosclerotic [17], antiobese [18], and other diverse pharmacological activities. Earlier studies revealed that most of compounds derived from 1,2,4-triazoles have been found to be significant anticonvulsant [19] and tranquillizing agents [20]. Furthermore, compounds 1a¨Ce in Figure 1 which contain [1,2,4]triazolo[4,3-a]quinoxaline moiety showed promising anticonvulsant activity [21]. Figure 1 We describe the synthesis and biological evaluation of novel [1,2,4]triazolo[4,3-a]quinoxaline derivatives expected to have anticonvulsant activity starting from 1,2-diaminobenzene and oxalic acid via quinoxaline ring build-up. 2. Results and Discussion 2.1. Chemistry The [1,2,4]triazolo[4,3-a]quinoxaline derivatives were prepared using established methodology as shown in Scheme 1. 2,3-Dichloroquinoxaline (3) was prepared by chlorination of 2,3-dihydroxyquinoxaline (2), which in turn was prepared by the condensation of the commercially available 1,2-diaminobenzene with oxalic acid in aqueous hydrochloric acid. Treatment of 3 with hydrazine hydrate yielded the corresponding 3-hydrazino compound, 4, which was subjected to ring closure to 5 by treatment with triethyl orthoformate. Reaction of 5 with thiourea in absolute ethanol afforded the isothiouronium intermediate which upon basic hydrolysis yielded [1,2,4]triazolo[4,3-a]quinoxaline-4-thiol (6). The potassium salt 7 was obtained after treatment of 6 with alcoholic KOH in a quantitative yield. Scheme 1 Reaction of the potassium salt 7 with substituted aniline in DMF gave the corresponding anilide 8a¨Cd, and its reaction with alkyl
%U http://www.hindawi.com/journals/isrn.organic.chemistry/2013/587054/