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 reacted with polyhydroxy aspartamide-type polymers, i.e. poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)] (PHEA) and poly[alpha,beta-(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.
Zovko
M
M
Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovacica, 1, 10000, Zagreb, Croatia.
Zorc
B
B
Lovrek
M
M
Boneschans
B
B
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002855:Chromatography, Thin Layer; D005279:Fenoprofen / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011102:Polyhydroxyethyl Methacrylate / Q000031:analogs & derivatives*; D011355:Prodrugs; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011355:Prodrugs; D011102:Polyhydroxyethyl Methacrylate; C023037:poly(2-hydroxyethyl acrylate); D005279:Fenoprofen