RESUMO
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.
Assuntos
Anti-Inflamatórios não Esteroides/química , Fenoprofeno/química , Poli-Hidroxietil Metacrilato/análogos & derivados , Pró-Fármacos , Cromatografia em Camada Fina , Espectroscopia de Ressonância Magnética , Espectrofotometria Infravermelho , Espectrofotometria UltravioletaRESUMO
The synthesis and spectroscopic characterisation of various gemfibrozil esters 3 and amides 4 are described. In the first step gemfibrozil was reacted with N-1-benzotriazolecarboxylic acid chloride (1) yielding gemfibrozil benzotriazolide (2). Compound 2 readily reacted with alcohols and amines to form the corresponding esters 3 and amides 4, potential prodrugs of the well known hypolipaemic drug gemfibrozil. The quantitative structure property relationship (QSPR) was studied in the series of gemfibrozil esters and amides. The following topological descriptors and physicochemical parameters were used: Wiener number (W), connectivity index (l chi v), relative molecular mass (M(r)), van der Waals volume (Vw) and parameters of lipophilicity (log P and RM).
Assuntos
Genfibrozila/análogos & derivados , Genfibrozila/farmacologia , Hipolipemiantes/farmacologia , Algoritmos , Fenômenos Químicos , Físico-Química , Cromatografia em Camada Fina , Genfibrozila/química , Hipolipemiantes/química , Espectroscopia de Ressonância Magnética , Peso Molecular , Relação Quantitativa Estrutura-Atividade , Análise de Regressão , Espectrofotometria InfravermelhoRESUMO
Gemfibrozil is covalently linked to two similar polymers: poly[alpha,beta-(N-2-hydroxyethyl-DL-aspartamide)] and poly[alpha,beta-(N-3-hydroxypropyl-DL-aspartamide)]. The synthesised polymer drug conjugates differ in average molecular mass, type of covalent bonding, length of spacer, drug-loading and solubility.
