N-ALKENYL-3-HYDROXYBENZO(B)THIOPHENE-2- CARBOXAMIDE DERIVATIVES AS DUAL CYCLOOXYGENASE AND LIPOXYGENASE INHIBITORS

摘要

1737M/0677A 17023IA TITLE OF THE INVENTION N-ALKENYL-3-HYDROXYBENZO¢b!THIOPHENE-2-CARBOXAMIDE DERIVATIVES AS DUAL CYCLOOXYGENASE AND LIPOXYGENASE INHIBITORS N-Alkenyl-3-hydroxybenzo¢b!thiophene-2-carboxamide derivatives have been prepared by: 1) treating a substituted 2-halobenzoate with thioacetamide followed by N-alkenylation with appropriate agents, such as aldehydes, ketones, enol ethers, epoxides, acetals or ketals; 2) treating a substituted thiosalicylate with an appropriately substituted haloacetamide, followed by dehydration; and 3) further synthetic modification of compounds prepared above. 1737M/0677A - 2 - 17023IA These compounds have been found to be effective inhibitors of both cyclooxygenase and lipoxygenase and thereby useful in the treatment of pain, fever, inflammation, arthritic conditions, asthma, allergic disorders, skin diseases, cardiovascular disorders, psoriasis, inflammatory bowel disease, glaucoma or other prostaglandins and/or leukotriene mediated diseases. Furthermore, these compounds have been found to exhibit cytoprotective activity which does not involve the inhibition of gastric acid secretion but can be used at relatively low dosages for increasing the resistance of gastro-intestinal mucosa to strong irritants.