title: Direct reaction of amides with nitric oxide to form diazeniumdiolates.
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.
authors.affiliation: Drug Design Section, Chemical Biology Laboratory, National Cancer Institute , Frederick, Maryland 21702, United States.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Holland
authors.forename: John R
authors.initials: JR
authors.lastname: Klose
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Deschamps
authors.forename: Zhao
authors.initials: Z
authors.lastname: Cao
authors.forename: Larry K
authors.initials: LK
authors.lastname: Keefer
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Saavedra
mesh_terms: D000577:Amides / Q000737:chemistry*; D001391:Azo Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*
chemical_list: D000577:Amides; D001391:Azo Compounds; D011725:Pyridines; C452539:diazeniumdiolate; D009569:Nitric Oxide