V-PROLI/NO, a Prodrug of the Nitric Oxide Donor, PROLI/NO

V-PROLI/NO, a Prodrug of the Nitric Oxide Donor, PROLI/NO

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...

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Veröffentlicht in:Organic letters 2007-08, Vol.9 (17), p.3409-3412
Hauptverfasser: Chakrapani, Harinath, Showalter, Brett M, Kong, Li, Keefer, Larry K, Saavedra, Joseph E
Format: Artikel
Sprache:eng
Schlagworte:
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
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Zusammenfassung: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 O 2 -vinyl derivative, V-PROLI/NO. Metabolism of V-PROLI/NO by liver microsomes enriched in human cytochrome P450 isoforms was demonstrated.
ISSN:1523-7060
1523-7052
DOI:10.1021/ol701419a