Benzofuran and benzothiophene derivatives, their use in inhibiting mammalian leukotriene biosynthesis, and pharmaceutical compositions containing these derivatives.

摘要

Novel benzofuran compounds have the formula CHEM in which each R1 is independently hydrogen or C1 to C6 alkyl R2 is hydrogen, C1 to C6 alkyl, -(CH2)n -Het-Y, or CHEM each R4 is independently C1 to C6 alkyl each R5 is independently H, C1 to C6 alkyl, or both R5s join to form a 5- or 6-membered ring with the N to which they are attached Het is a heterocyclic group selected from pyridine, pyrazine, pyrimidine, oxazole, pyrazole, oxadiazole, tetrazole, quinoline, thiophene, furan, pyrrole, thiazole, thiadiazole, or imidazole X is O, S, SO, SO2 Y, Y1, Y2, Y3, Y4 and Z are each independently H, halogen, OH. C1 to C6 alkyl, C2 to C6 alkenyl, -COOR1, -COR1, nitro, C1 to C6 alkoxy, C1 to C6 alkylthio, -CH2SR1, OCH2CO2R1, CHEM and each n is independently 0 to 10 with the provisos that: (a) not all of R1, R2, Y, Y1, Y2, Y3, Y4, and Z are simultaneously H (b) when up to 2 of R1, R2, Y, Y1, and Z are C1 to C2 alkyl, and the others of R1, R2, Y, Y1, and Z are H, then R3 is not OH and (c) when n in CHEM is O and one of R3, Y, Y1 or Z is OH, then R1 is not H or C1 to C2 alkyl. Their phamaceutically acceptable salts are also novel. These compounds are useful as inhibitors of mammalian leukotriene biosynthesis and are therefore useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders, inflammation. The compounds are also useful as analgesics and as cytoprotective agents. They are made into pharmaceutical compositions for such uses.