Pharmacologically active polymers, 17. Syntheses and characterization of polymeric derivatives of the antitumor agent methotrexate

摘要: Synthesis and characterization of polymeric derivatives the folic acid antagonist, Methotrexate, N-[4-(N-methyl-2,4-diamino-6-pteridinylmethylamino)benzoyl] glutamic (1a), a widely used antitumor agent, are described. Derivatives poly(L-lysine), poly(iminoethylene), poly(vinyl alcohol), carboxymethylcellulose with various contents (3–15 mole-%) substituted repeating units were prepared by polymer-analogous amidation transesterification dimethyl ester 1a N-[2-(N-methylmorpholinio)ethyl]carbodiimide p-toluenesulfonate as coupling reagent. By nucleophilic addition reactions pteridinyl amino groups under mild conditions, was bound without cross-linking to divinyl ether-maleic anhydride (DIVEMA) copolymers molecular weights. This copolymer appeared be particular interest carrier because its established immune-stimulating activity.—With exception alcohol) derivative, all polymers containing residue water soluble at physiological pH range. Besides convenient starting material for reactions, further dialkyl esters synthesized low weight model compounds study pharmacodynamic properties polymers, 1a. The purified membrane filtration, solvent extraction, reprecipitation; dialkylesters 1b–d characterized thin-layer chromatography, IR, NMR, UV mass spectra, elemental analysis. Preliminary results pharmacological studies DIVEMA also reported.