David G. Johns, Ti Li Loo
Mar 1, 1967
Citations
1
Influential Citations
73
Citations
Quality indicators
Journal
Journal of Pharmaceutical Sciences
Abstract
4-Amino-4-deoxy-N 10 -methylpteroylglutamic acid (methotrexate; MTX) is rapidly metabolized by rabbit liver aldehyde oxidase. The MTX metabolite, on oxidative cleavage with permanganate, yields a simple pteridine having the spectrophotometric and chromatographic properties of 2,4-diamino-7-hydroxy-6-pteridinecarboxylic acid. Alkaline hydrolysis of the latter at 70° slowly converts it to 2-amino-4,7-dihydroxy-6-pteridinecarboxylic acid. The nonpteridine moiety of the MTX metabolite is identical with the nonpteridine moiety of MTX. The biological properties of the MTX metabolite are compatible with those of a 2,4-diamino derivative of pteroylglutamate. In view of these findings, the structure, 4-amino-4-deoxy-7-hydroxy-N 10 -methylpteroylglutamic acid (7-hydroxy-MTX), is proposed for the MTX metabolite.