| 摘要 |
PURPOSE:To obtain the titled conjugate useful as a remedy for leukemia or solid tumor, etc., by reacting a methotrexate with a dehydrating condensing agent and reacting the reaction product with an alcohol to form an active ester of the methotrexate. CONSTITUTION:Methotrexate expressed by formula I is reacted with a dehydrating condensing agent, e.g. DDC, to form a cyclic intramolecular acid anhydride expressed by formula II (R is formula III), which is then reacted with an alcohol, e.g. N-hydroxysuccinimide, to afford an active ester of the methotrexate expressed by formula IV or V. The resultant active ester is then reacted with a protein, e.g. blood serum albumin, to give the aimed conjugate of the methotrexate with the protein. When an active ester obtained by reacting the methotrexate with an equimolar amount of the dehydrating condensing agent is used, the increase in molecular weight of the protein in the next step is suppressed to afford the aimed conjugate in high yield.
|
