title: Synthesis of the 7-hydroxy metabolites of methotrexate and 10-ethyl-10-deazaaminopterin.
abstract: The potent folate antagonists methotrexate and 10-ethyl-10-deazaaminopterin are oxidized in vivo to their 7-hydroxy derivatives. A specific cyanation at the C-7 position of the pteridine ring system using diethyl phosphorocyanidate converted the dimethyl esters of methotrexate and 10-ethyl-10-deazaaminopterin to the corresponding 7-cyano dimethyl ester derivatives, which were hydrolyzed to the 7-hydroxy metabolites.
authors.affiliation: Bio-Organic Chemistry Laboratory, SRI International, Menlo Park, CA 94025, USA.
authors.forename: M I
authors.initials: MI
authors.lastname: Dawson
authors.forename: D
authors.initials: D
authors.lastname: O'Krongly
authors.forename: P D
authors.initials: PD
authors.lastname: Hobbs
authors.forename: J R
authors.initials: JR
authors.lastname: Barrueco
authors.forename: F M
authors.initials: FM
authors.lastname: Sirotnak
mesh_terms: D000630:Aminopterin / Q000031:analogs & derivatives* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism*; D005493:Folic Acid Antagonists / Q000378:metabolism*; D008727:Methotrexate / Q000378:metabolism*; D010084:Oxidation-Reduction
chemical_list: D000970:Antineoplastic Agents; D005493:Folic Acid Antagonists; C040210:edatrexate; D000630:Aminopterin; D008727:Methotrexate