Piperazinealkanol Ester Derivatives of Indomethacin as Dual Inhibitors of 5-Lipoxygenase and Cyclooxygenase

Abstract

Piperazinealkanol ester derivatives of indomethacin were prepared and tested for inhibitory activities against 5-lipoxygenase (5-LO) and cyclooxygenase (CO). They inhibited 5-hydroxyeicosatetraenoic acid (5-HETE) formation by the cytosol of guinea pig polymorphonuclear leukocytes and thromboxane B2 (TXB2) formation by washed rabit platelet suspension. Of the test compounds, 2-[4-(2-hydroxyethyl)-l-piperazinyl]-l-phenylethyl l-(4-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetate dimaleate (II-8) was found to be the most active dual inhibitor of 5-LO and CO, and its inhibitory potency was higher than that of 2-[4-(3-hydroxypropyl)-l-piperazinyl]-ethyl [l-(4-chlorobenzoyl)-5-methoxy-2-methyl]-3-indolylacetate (CR-1015) (I), the lead compound. © 1994, The Pharmaceutical Society of Japan. All rights reserved.