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-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.
Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, Frederick, Maryland 21702, USA.
Harinath
H
Chakrapani
Brett M
BM
Showalter
Li
L
Kong
Larry K
LK
Keefer
Joseph E
JE
Saavedra
D003577:Cytochrome P-450 Enzyme System; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000138:chemical synthesis* / Q000378:metabolism; D011355:Prodrugs / Q000138:chemical synthesis* / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D020033:Protein Isoforms; D014753:Vinyl Compounds
D020030:Nitric Oxide Donors; D011355:Prodrugs; D020033:Protein Isoforms; D014753:Vinyl Compounds; C102043:proline-nitric oxide; D003577:Cytochrome P-450 Enzyme System; D011392:Proline