N-ALKENYL-3-HYDROXYBENZO¬BTHIOPHENE-2- CARBOXAMIDE DERIVATIVES AS DUALCYCLOOXYGENASE AND LIPOXYGENASE INHIBITORS

摘要

1737M/0677A17023IATITLE OF THE INVENTIONN-ALKENYL-3-HYDROXYBENZO[b]THIOPHENE-2-CARBOXAMIDE DERIVATIVES AS DUAL CYCLOOXYGENASE ANDLIPOXYGENASE INHIBITORSABSTRACT OF THE DISCLOSUREN-Alkenyl-3-hydroxybenzo[b]thiophene-2-carboxamide derivatives have been prepared by:1) treating a substituted 2-halobenzoate withthioacetamide followed by N-alkenylationwith appropriate agents, such as aldehydes,ketones, enol ethers, epoxides, acetals orketals;2) treating a substituted thiosalicylate withan appropriately substituted haloacetamide,followed by dehydration; and3) further synthetic modification of compoundsprepared above.1737M/0677A - 2 - 17023IAThese compounds have been found to be effectiveinhibitors of both cyclooxygenase and lipoxygenase andthereby useful in the treatment of pain, fever,inflammation, arthritic conditions, asthma, allergicdisorders, skin diseases, cardiovascular disorders,psoriasis, inflammatory bowel disease, glaucoma orother prostaglandins and/or leukotriene mediateddiseases. Furthermore, these compounds have beenfound to exhibit cytoprotective activity which doesnot involve the inhibition of gastric acid secretionbut can be used at relatively low dosages forincreasing the resistance of gastro-intestinal mucosato strong irritants.