Tropesin: a new potential anti-rheumatic ester of indometacin

Abstract

Indometacin is one of the most widely used non-steroidal anti-inflammatory drugs. Its excellent anti-inflammatory efficacy on the one hand, but its relatively high toxicity on the other hand, have initiated several working teams to search for derivatives of indometacin with more advantageous therapeutic properties. In the course of many years a great variety of analogues of indometacin have been synthesized, and esters doubtlessly belong among the most interesting compounds studied. During our work in this sphere, other working teams have applied for patents for glycollic acid ester¹ and trichloro-ethyl ester of indometacin². From papers published so far it is evident that no new therapeutically usable derivative has been synthesized as yet that would retain the efficacy of indometacin and have a lower toxicity. Our research, therefore, has been mainly focused on this aspect. At the Research Institute for Pharmacy and Biochemistry, Prague, a series of indometacin esters with two types of hydroxy compounds, namely primary alcohols and phenols, was synthesized. The products were assessed using a method based on measuring the rate of cleavage of esters to the parent indometacin and the appropriate alcohol by action of serum esterases in vitro.