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 beta -alanine fenoprofenamide (3b) and their benzotriazolides 6a and 6b. Compounds 2 and 6 readily react ed with polyhydroxy aspartamide-type polymers, i.e. poly[alpha,beta-(N-2-hy droxyethyl-DL-aspartamide)] (PHEA) and poly[alpha,beta-(N-3-hydroxypropyl-D L-aspartamide)] (PHPA) forming conjugates 5, 8a,b and 9a,b. respectively. C onjugate I I was obtained by partial aminolysis of poly-DL-(2,5-dioxo-1,3-p yrrolidinediyl) (PSI) with 2-aminoethyl fenoprofenamide (3c), followed by t otal aminolysis with 2-hydroxyethylamine. The synthesised polymer-drug conj ugates differed in type of covalent bounding, type and/or length of spacer and drug-loading. (C) 2001 Elsevier Science B.V. All rights reserved.