Synthesis and antimicrobial activity of certain 6H-1,2,4-oxadiazin-3(2H)-ones

Abstract

Treatment of 6H-1,2,4-oxadiazin-3(2H)-one-5(4H)-thione (2) with hydroxylamine, hydrazine, methylamine, or benzylamine afforded the corresponding N5-substituted 5-amino-6H-1,2,4-oxadiazin-3(2H)-ones 3c-f. Refluxing a dioxane solution of 6H-1,2,4-oxiazine-3,5(2H,4H)-dione (1) with benzylamine or aminodiphenylmethane and hexamethyldisilazane in the presence of ammonium sulfate gave 5-benzylamino-6H-1,2,4-oxadiazin-3(2H)-one (3f) and the corresponding 5-diphenylmethylamino derivative 3g. Reaction of 1 with methyl iodide, benzyl chloride, dihydropyran, dihydrofuran, or benzyloxycarbonyl chloride afforded the corresponding 2-substituted 6H-1,2,4-oxadiazine-3,5(2H,4H)-diones 6a-e. Reaction of 2-methyl-6H-1,2,4-oxadiazine-3,5(2H,4H)-dione (6a) or the corresponding 2-benzyl derivative 6b with phosphorus pentasulfide in dioxane gave 2-methyl-6H-1,2,4-oxadiazin-3(2H)-one-5(4H)-thione (8a) and the corresponding 2-benzyl derivative 8b, respectively. Reaction of 8a with ammonia in dioxane afforded 2-methyl-5-amino-6H-1,2,4-oxadiazin-3(2H)-one (9). The degree of in vitro activity and the presence of antibacterial activity in the urine of animals given 5-amino-6H-1,2,4-oxadiazin-3(2H)-one (3a) by oral route of administration prompted selection of this compound for further study.

Pyrimidooxadiazine and triazolopyrimidooxadiazine derivatives: Synthesis and cytotoxic evaluation in human cancer cell lines

“…7 Chloro 1,5 dimethyl 3 phenyl 1H pyrimido [4,5 e] [1,3,4]oxadiazine (III) was prepared by the reaction of 5 bromo 2 chloro 6 methyl 4 (1 meth ylhydrazino)pyrimidine (II) with benzoyl chloride in the presence of K 2 CO 3 according to previous published method [13]. Subsequent treatment of compound (III) with pyrrolidine in boiling ethanol led to the replace ment of chorine atom to give 1,5 dimethyl 3 phenyl 7 (pyrrolidin 1 yl) 1H pyrimido [4,5 e] [1,3,4]oxadiaz ine (IV).…”

“…Oxadiazines bearing heteroatoms at positions 1, 2, and 4 or 1, 3, and 4 are interesting and promising het erocyclic compounds, as they possess diverse biologi cal activities [1]. There are some reports in the litera ture on their cardiovascular, antibacterial, insecticidal, and anticonvulsive activities [2,3].…”

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In vitro antiproliferative activities of some pyrimido [4,5 e] [1,3,4]oxadiazine and [1,2,4]triaz olo[4',3':1,2]pyrimido[4,5 e][1,3,4]oxadiazine derivatives were examined in human malignant cancer cell lines. All synthesized compounds inhibited the growth of malignant cells in a dose dependent manner, but among them 1,5,7 trimethyl 3 phenyl 1H [1,2,4]triazolo[4',3':1,2]pyrimido[4,5 e][1,3,4]oxadiazine and [(1,5 dimethyl 3 phenyl 1H [1,2,4]triazolo[4',3':1,2]pyrimido[4,5 e] [1,3,4]oxadiazin 7 yl)sulfa nyl]acetonitrile, both with triazole moiety, were found to be more effective than other compounds; they also induced a sub G1 peak in the flow cytometry histogram of treated cells compared to controls, indicat ing that apoptotic cell death is involved in toxicity they induce.

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“…All synthesized compounds inhibited the growth of malignant cells in a dose dependent manner, but among them 1,5,7 trimethyl 3 phenyl 1H [1,2,4]triazolo[4',3':1,2]pyrimido[4,5 e][1,3,4]oxadiazine and [(1,5 dimethyl 3 phenyl 1H [1,2,4]triazolo[4',3':1,2]pyrimido[4,5 e] [1,3,4]oxadiazin 7 yl)sulfa nyl]acetonitrile, both with triazole moiety, were found to be more effective than other compounds; they also induced a sub G1 peak in the flow cytometry histogram of treated cells compared to controls, indicat ing that apoptotic cell death is involved in toxicity they induce. The results showed that compounds with triazole moiety fused to pyrimido[4,5 e] [1,3,4]oxadiazine derivatives are more active than those bearing chlorine or pyrrolidine groups at C 7 position. …”

Synthesis and antibacterial evaluations of new pyridazino[4,3‐e][1,3,4]oxadiazines

“…They have a diverse biological properties [1] such as inhibitors of bacterial growth [2], antimicrobial agents [2,3], and also useful intermediates in the synthesis of tenidap prodrugs or b-lactam antibiotics, especially, in the synthesis of carbapenems and penems [4,5], cardiovascular antibacterial, miticidal, nematocidal, acricidal, insecticidal, and anticonvulsive activities [6,7].…”