23-d Synthesis and characterization of new antifolate having a furo23-dpyrimidine derivatives

摘要

PURPOSE: Provided is a novel derivative of aminopterin methotrexate(amethopterin:MTX) and homofolic acid which are antimetabolites and act as antagonist of folic acid. Also, its manufacturing method is provided. CONSTITUTION: Aminopteridin derivative compound is represented by the formula(I), wherein R is hydrogen or methyl; and R1 and R2 are respectively hydrogen, Na, methyl ethyl or isopropyl. Its manufacturing method comprises the steps of: introducing Sandmeyer reaction to obtain a compound of the formula(3); reducing the compound of the formula(3) to NaBH4 in ethanol; adding the resultant compound furopyrimidine derivative of the formula(2) to obtain pteroic acid derivative of the formula(4); reacting the pteroic acid derivative of the formula(4) with diethyl L-glutamate in the presence of DMF(dimethylformamide) using DDC or DEPC(diethylphosphoro-cyanidate) to obtain a compound of the formula(5); and reacting the resultant compound with =S¬+-CH3, if necessary hydrolyzing the resultant compound, to obtain a compound of the formula(I).