Synthesis of analogues of folic acid, aminopterin and methotrexate as antitumour agents.

摘要: Publisher Summary This chapter discusses the syntheses of folic acid, aminopterin, and methotrexate analogs in which an intact L-glutamic acid side-chain is present while simultaneously varying pteridine ring moiety, C-9, N- 10 bridge and/or benzoyl group. Several are known only remaining structural feature molecule p-aminobenzoylglutamic moiety. Biological results discussed those cases where analog has significant activity tumor systems relative to (MTX) or aminopterin (AP). Of many classes deazaFA derivatives investigated, none received more attention resulted promising candidate drugs than 5,8-dideaza (quinazoline) analogs. Methylation (FA) with a 4-molar excess methyl iodide gave low yield tetramethyl derivative. A Dimroth rearrangement brought about by base at room temperature then hydrolysis esters having taken place under conditions rearrangement.