Direct reaction of amides with nitric oxide to form diazeniumdiolates
Ryan J Holland1, John R Klose, Jeffrey R Deschamps
1Drug Design Section, Chemical Biology Laboratory, National Cancer Institute , Frederick, Maryland 21702, United States.
Abstract:
We report the apparently unprecedented direct reaction of nitric oxide (NO) with amides to generate ions of structure R(C═O)NH-N(O)═NO(-), with examples including R = Me (1a) or 3-pyridyl (1b). The sodium salts of both released NO in pH 7.4 buffer, with 37 °C half-lives of 1-3 min. As NO-releasing drug candidates, diazeniumdiolated amides would have the advantage of generating only 1 equiv of base on hydrolyzing exhaustively to NO, in contrast to their amine counterparts, which generate 2 equiv of base.
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