V-PROLI/NO, a prodrug of the nitric oxide donor, PROLI/NO

Org Lett. 2007 Aug 16;9(17):3409-12. doi: 10.1021/ol701419a. Epub 2007 Jul 20.

Abstract

The sensitivity to decomposition of the nitric oxide (NO) donor ion, 1-[2-(carboxylato)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate (PROLI/NO), complicates direct electrophilic substitution to form useful prodrug derivatives. A modified general synthetic approach involving 1-[2-(hydroxymethyl)pyrrolidin-1-yl]diazen-1-ium-1,2-diolate ion (structure A, above) was used to prepare several PROLI/NO prodrugs including the previously inaccessible O2-vinyl derivative, V-PROLI/NO. Metabolism of V-PROLI/NO by liver microsomes enriched in human cytochrome P450 isoforms was demonstrated.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Cytochrome P-450 Enzyme System
  • Humans
  • Microsomes, Liver / metabolism
  • Nitric Oxide Donors / chemical synthesis*
  • Nitric Oxide Donors / metabolism
  • Prodrugs / chemical synthesis*
  • Prodrugs / metabolism
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis
  • Proline / metabolism
  • Protein Isoforms
  • Vinyl Compounds

Substances

  • Nitric Oxide Donors
  • Prodrugs
  • Protein Isoforms
  • Vinyl Compounds
  • proline-nitric oxide
  • Cytochrome P-450 Enzyme System
  • Proline