4‐Cyano‐2‐oxo‐1,2,4‐oxadiazolo[2,3‐<i>a</i>]quinoxaline 5‐<i>N</i>‐oxides. New synthetic method and reaction with alcohols. Potential cytotoxic activity

Abstract

Abstract Several quinoxaline 1,4‐di‐ N ‐oxides have been shown to be efficient and selective cytotoxins for hypoxic cells. We present now a series of 4‐cyano‐2‐oxo‐1,2,4‐oxadiazolo[2,3‐ a ]quinoxaline 5‐ N ‐oxides 2a‐2k . They were prepared starting from 3‐amino‐2‐quinoxalinecarbonitrile 1,4‐di‐ N ‐oxides 1a‐1k and 2‐chloroethyl isocyanate in dry dioxane at 100–110°. A reaction mechanism is proposed. The treatment of 1a with phenyl isocyanate afforded 2a . Reaction of 2c with silica gel yielded 1c . Compounds 2a‐2g were heated in the presence of ethanol and 2‐propanol giving the corresponding carbamates 3a‐3g and 4a‐4g . Compound 2d was already obtained by heating a mixture of 1d and ethyl chloroformiate. Compound 2b was prepared when the carbamate 3b was heated at 150°. Quinoxalines were tested as cytotoxic agents both in oxic and hypoxic cells. The most interesting compounds were 3g and 4g .