“…Diazetine dioxides are prepared by the oxidation of the corresponding bishydroxyamines with NaOBr in aqueous base. [452][453][454][455][456] 3-Bromo-3,4,4-trimethyl-3,4-dihydrodiazete 1,2-dioxide (43) and 3-bromo-4-methyl-3,4-hexamethylene-3,4-dihydro-diazete 1,2-dioxide (44) are commercially available.…”
Section: Diazetine Dioxidesmentioning
confidence: 99%
“…Compound 42 has been extensively used as a triplet quencher. − Recently, the biological activity and NO release mechanism of DD have been studied. Diazetine dioxides are prepared by the oxidation of the corresponding bishydroxyamines with NaOBr in aqueous base. − 3-Bromo-3,4,4-trimethyl-3,4-dihydrodiazete 1,2-dioxide ( 43 ) and 3-bromo-4-methyl-3,4-hexamethylene-3,4-dihydro-diazete 1,2-dioxide ( 44 ) are commercially available. 18 19 …”
“…Diazetine dioxides are prepared by the oxidation of the corresponding bishydroxyamines with NaOBr in aqueous base. [452][453][454][455][456] 3-Bromo-3,4,4-trimethyl-3,4-dihydrodiazete 1,2-dioxide (43) and 3-bromo-4-methyl-3,4-hexamethylene-3,4-dihydro-diazete 1,2-dioxide (44) are commercially available.…”
Section: Diazetine Dioxidesmentioning
confidence: 99%
“…Compound 42 has been extensively used as a triplet quencher. − Recently, the biological activity and NO release mechanism of DD have been studied. Diazetine dioxides are prepared by the oxidation of the corresponding bishydroxyamines with NaOBr in aqueous base. − 3-Bromo-3,4,4-trimethyl-3,4-dihydrodiazete 1,2-dioxide ( 43 ) and 3-bromo-4-methyl-3,4-hexamethylene-3,4-dihydro-diazete 1,2-dioxide ( 44 ) are commercially available. 18 19 …”
“…Reagents and Instruments. Compounds 1a , 2a , 3 , 4 ,2b 5a , 5b , and 7 1 were synthesized according to literature procedures. Purity of the DD samples used for measurement was checked by HPLC (see below).…”
Section: Methodsmentioning
confidence: 99%
“…3,4-Dihydrodiazete 1,2-dioxides (diazetine dioxides, DD) were described for the first time about 20 years ago; however, their biological activity was studied only recently . These compounds were found to exert strong vasorelaxant and antiaggregant effects …”
mentioning
confidence: 99%
“…These compounds were found to exert strong vasorelaxant and antiaggregant effects 1b, and the rate constants of this reaction were measured for a series of DD in aqueous solutions 2b. However, the rate constants were in the range of 10 -7 s -1 , too low to account for the strong vasorelaxation induced by DD. 2a,d Typical concentrations of diazetine dioxides causing significant vasodilation were determined to be in the range of 10 -6 M …”
In this work we studied the mechanism of nitric oxide (NO) release underlying the vasorelaxant and antiaggregant effect of 3,4-dihydrodiazete 1,2-dioxides (DD). Six derivatives were included in the investigations, namely, 3-bromo- and 3-chloro-3,4,4-trimethyl-DD (1a,b), 3-bromo- and 3-chloro-4-methyl-3,4-hexamethylene-DD (2a,b), 3,3,4,4-tetramethyl-DD (3), and 3-methyl-3,4-hexamethylene-DD (4), and their reactivity toward thiols was analyzed. The 3-bromo- and 3-chloro-DD derivatives were found to react with thiols; this reaction can lead to NO formation, DD 2a being the most reactive compound. 2-(Hydroxyamino)-2-methylbutan-3-one oxime (5a) and 2-hydroxy-2-methylbutan-3-one oxime (6) were the main products isolated from the reaction of 1a with cysteine. Reaction rates of DD with thiols were dependent upon pH and concentration of the reagents. Maximum rates of NO release corresponded to thiol concentrations in the range of 1 mM. Consistent with reaction kinetics data and products isolated, a reaction mechanism was proposed. Addition of 2a to bovine aortic endothelial cells led to strong NO release indicating a reaction with endogenous thiols. In rat mesenterial arteries, the vasorelaxant action of 2a was only slightly influenced by addition of thiol to the incubation medium. For the most reactive DD derivatives, cytotoxic effects were observed at concentrations roughly 2 orders of magnitude higher than those inducing vasorelaxation.
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