A new class of co-drugs were synthesised by joining antioxidant edaravone with a vasodilating substructure containing NO-donor nitrooxy functions, and characterised for their stability in different media, lipophilicity and permeability profile. The products display good stability in water/co-solvent at different pH. Conversely, they are rapidly metabolised into edaravone and NO-donor moietieswhen incubated in human serum or rat-liver homogenates. In the latter conditions time dependent production of nitrite/nitrate (NOx) occurs. The compounds display wide-ranging lipophilicity. PAMPA studies predict good gastrointestinal absorption for a number of these compounds. The title products are potentially useful for treating ROSrelated conditions accompanied by decreased NO availability.

Synthesis physicochemical profile and PAMPA study of new NO-donor edaravone co-drugs

ROLANDO, Barbara;FILIERI, Andrea;CHEGAEV, Konstantin;LAZZARATO, Loretta;GIORGIS, Marta;FRUTTERO, Roberta;GASCO, Alberto
2012

Abstract

A new class of co-drugs were synthesised by joining antioxidant edaravone with a vasodilating substructure containing NO-donor nitrooxy functions, and characterised for their stability in different media, lipophilicity and permeability profile. The products display good stability in water/co-solvent at different pH. Conversely, they are rapidly metabolised into edaravone and NO-donor moietieswhen incubated in human serum or rat-liver homogenates. In the latter conditions time dependent production of nitrite/nitrate (NOx) occurs. The compounds display wide-ranging lipophilicity. PAMPA studies predict good gastrointestinal absorption for a number of these compounds. The title products are potentially useful for treating ROSrelated conditions accompanied by decreased NO availability.
BIOORGANIC & MEDICINAL CHEMISTRY
20
2
841
850
http://www.sciencedirect.com/
Nitrooxy-acyl derivatives of edaravone; Co-drugs; Lipophilicity profile; In vitro permeability profile
Barbara Rolando; Andrea Filieri; Konstantin Chegaev; Loretta Lazzarato; Marta Giorgis; Claudio De Nardi; Roberta Fruttero; Sophie Martel; Pierre-Alain Carrupt; Alberto Gasco
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/93332
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