| 摘要 |
N-Alkenyl-3-hydroxybenzo [b] thiophene-2-carboxamide derivatives of formula) <CHEM> and their pharmaceutically acceptable salts, are novel. In the formula, each of R, R<1>, R<2>, R<3> and R<4> is selected from various hydrocarbons (including heteroaryl), acyl, and acyl-substituted hydrocarbon groups and their ring-substituted derivatives; or R<1>, R<2> and R<3> can be halo, or R<1> and R<2> joined to form certain tricyclic bivalent residues, or R<4> is -CR<1>=CR<2>R<3>, and @ is 0, 1, or 2. These compounds are 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 halocetamide, followed by dehydration; and (3) further synthetic modification of compounds prepared above. 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 as relatively low dosages for increasing the resistance of gastro-intestinal mucosa to strong irritants. They are included in pharmaceutical compositions. |
