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4‐Cyano‐2‐oxo‐1,2,4‐oxadiazolo[2,3‐ a ]quinoxaline 5‐ N ‐oxides. New synthetic method and reaction with alcohols. Potential cytotoxic activity
Author(s) -
Martínez Crespo F. J.,
Palop J. A.,
Sainz Y.,
Narro S.,
Senador V.,
González M.,
De Ceráin A. López,
Monge A.,
Hamilton E.,
Barker A. J.
Publication year - 1996
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570330620
Subject(s) - chemistry , quinoxaline , cytotoxic t cell , combinatorial chemistry , organic chemistry , medicinal chemistry , stereochemistry , in vitro , biochemistry
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 .