Gemfibrozil ester and amide derivatives : synthesis, spectroscopic characterisation and QSPR

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).