| abstract |
Benzofuran derivatives are useful as inhibitors of mammalian leuktoriene biosynthesis. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders, inflammation. The compounds are also useful as analgesics and as cytoprotective agents, and for these uses are made into pharmaceutical compositions. The compounds of the invention have the formulan wherein:n each R 1 is independently hydrogen or C 1 to C 6 alkyl; R 2 is hydrogen, C 1 to C 8 alkyl, -(CH 2 ) n -het-Y, -(CH 2 ) n -Q or - CH- Q, C H 3 where Q isn R3 is hydroxyl,n , OCOCH 2 CH 2 COOH, OSO 3 H, or OPO 3 H 2 ; each R 4 is independently C 1 to C 6 alkyl; each R 5 is independently H, C 1 to C 6 alkyl, or both R 5 s 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 0, S, SO, SO 2 ; Y, Y 1 , Y 2 , Y 3 , Y 4 and Z are each independently H, halogen, OH. C 1 to C 6 alkyl, C 2 to C 6 alkenyl, C 1-6 hydroxyalkyl, -COOR 1 , -COR 1 , nitro, carboxy (C 1-6 alkyl), C 1 to C 6 alkoxy, C 1 to C 6 alkylthio, -CH 2 SR 1 , OCH 2 CO 2 R 1 ,n n and each n is independently 0 to 10; with the provisos that:n (a) not all of R 1 , R 2 , Y, Y 1 , Y 2 , Y 3 , Y 4 , and Z are simultaneously H; (b) when up to 2 of R 1 , R 2 , Y, Y 1 , and Z are C 1 to C 2 alkyl, and the others of R 1 , R 2 , Y, Y 1 , and Z are H, then R 3 is not OH; and (c) when n inn is O and one of R 3 , Y, Y 1 or Z is OH, then R i is not H or C i to C 2 alkyl; or are acid-addition salts thereof. |