engleski

Macromolecular prodrugs. IX. Synthesis of polymer-fenoprofen conjugates

Synthesis of several polymer-fenoprofen conjugates is described. Fenoprofen was first chemically modified into benzotriazolide 2 and amino acid amide derivatives: glycine fenoprofenamide (3a) and b-alanine fenoprofenamide (3b) and their benzotriazolides 6a and 6b. Compounds 2 and 6 readily reacted with polyhydroxy aspartamide-type polymers, i.e. poly[a, b-(N-2-hydroxyethyl-DL-aspartamide)] (PHEA) and poly[a, b-(N-3-hydroxypropyl-DL-aspartamide)] (PHPA) forming conjugates 5, 8a, b and 9a, b, respectively. Conjugate 11 was obtained by partial aminolysis of poly-DL-(2, 5-dioxo-1, 3-pyrrolidinediyl) (PSI) with 2-aminoethyl fenoprofenamide (3c), followed by total aminolysis with 2-hydroxyethylamine. The synthesised polymer-drug conjugates differed in type of covalent bounding, type and/or length of spacer and drug-loading.

fenoprofen; polymer-drug conjugate; macromolecular prodrug; spacer; poly[a; b-(N-2-hydroxyethyl-DL-aspartamide)]; poly[a; b-(N-3-hydroxypropyl-DL-aspartamide)]; poly[a; b-(N-2-aminoethyl-DL-aspartamide]-poly[a; b-(N-2-hydroxyethyl-DL-aspartamide)]-copolymer

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