J. Hovinen, R. Silvennoinen, J. Vilpo
Jan 23, 1998
Citations
0
Influential Citations
6
Citations
Journal
Chemical research in toxicology
Abstract
N,N-Bis(2-chloroethyl)-p-aminophenylbutyric acid (chlorambucil, 1) is an orally administered drug widely used in the chemotherapy of chronic lymphocytic leukemia. It is converted in gastric juice into three stable metabolites, which were characterized as N,N-bis(2-hydroxyethyl)-p-aminophenylbutyric acid (4), N-(2-hydroxyethyl)-N-[2-(thiocyano)ethyl]-p-aminophenylbutyric+ ++ acid (5), and N,N-bis[2-(thiocyano)ethyl]-p-aminophenylbutyric acid (6). 4 is the product of chloroambucil hydrolysis, while 5 and 6 are results of the reaction of 1 with saliva-derived thiocyanate ion. The destabilizing effect of low gastric oxonium ion concentration on 1 is also demonstrated.