Metabolite of 4-amino-4-deoxy-N10-methylpteroylglutamic acid (methotrexate)

✍ Scribed by David G. Johns; Ti Li Loo

• Book ID: 102395365
• Publisher: John Wiley and Sons
• Year: 1967
• Tongue: English
• Weight: 417 KB
• Volume: 56
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600560310

✦ Synopsis

Amin0-4-deoxy-N'~-methylpteroylglutamic acid (methotrexate; M T X ) 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-G-pteridinecarboxylic acid. Alkaline hydrolysis of the latter at 70" slowly converts it to 2amino-4,7-dihydroxy-G-pteridinecarboxylic acid. T h e 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-N1a-methylpteroylglutamic acid (7-hydroxy-MTX), is proposed for the MTX metabolite.

HE FOLIC ACID analog 4-amino-4-deoxy-N'O-Tmethylpteroylglutamic acid (methotrexate;