Preparation, characterization and in vivo conversion of new water-soluble sulfenamide prodrugs of carbamazepine.
Improved synthetic methods are reported for the preparation of sulfenamide derivatives of carbamazepine (CBZ) for evaluation as prodrugs. These sulfenamide prodrugs were designed to rapidly release CBZ in vivo by cleavage of the sulfenamide bond by chemical reaction with glutathione and other sulfhydryl compounds. Physicochemical characterization and in vivo conversion of a new prodrug of CBZ was evaluated to further establish the proof of concept of the sulfenamide prodrug approach.
Hemenway
Jeffrey N
JN
Department of Pharmaceutical Chemistry, 2095 Constant Avenue, University of Kansas, Lawrence, KS 66047, USA.
Nti-Addae
Kwame
K
Guarino
Victor R
VR
Stella
Valentino J
VJ
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D002220:Carbamazepine / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D008956:Models, Chemical; D011355:Prodrugs / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism*; D051381:Rats; D012995:Solubility; D013416:Sulfamerazine / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism*; D014867:Water / Q000737:chemistry*
D000927:Anticonvulsants; D011355:Prodrugs; C471392:sulfenamide; D014867:Water; D002220:Carbamazepine; D005978:Glutathione; D013416:Sulfamerazine