Direct reaction of amides with nitric oxide to form diazeniumdiolates

J Org Chem. 2014 Oct 3;79(19):9389-93. doi: 10.1021/jo501670e. Epub 2014 Sep 22.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amides / chemistry*
  • Azo Compounds / chemical synthesis*
  • Azo Compounds / chemistry*
  • Molecular Structure
  • Nitric Oxide / chemistry*
  • Pyridines / chemistry*

Substances

  • Amides
  • Azo Compounds
  • Pyridines
  • diazeniumdiolate
  • Nitric Oxide