Patent TW-382594-B (TW)
Title: Pharmaceutical compositions comprising carboxylic acid derivatives for use as inhibitors of endothelin receptors
Inventor: BAUMANN ERNST
IPC: A61K31/505
Filed: 1995-03-28
Granted: 2000-02-21
Abstract: Pharmaceutical compositions for use as inhibitors of endothelin receptors comprising carboxylic acid derivatives of general formula I, (I), where R is formyl, CO2H or a radical which can be hydrolyzed to COOH, and the remaining substituents have the following meanings: R2 is halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy or C1-C4-alkylthio; X is nitrogen or CR14 where R14 is hydrogen or, together with R3, forms a 3- or 4-membered alkylene or alkenylene chain in R3 is halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio or R3 is linked to R14 as indicated above to form a 5- or 6-membered ring; R4 is C1-C10-alkyl which can carry from one to five halogen atoms and/or one of the following radicals: C1-C4-alkoxy, C1-C4-alkylthio, cyano, C1-C8-alkylcarbonyl, C1-C8-alkoxy-carbonyl, phenyl, phenoxy or phenylcarbonyl, where the phenyl radicals in turn can carry from one to five halogen atoms and/or from one to three of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and/or C1-C4-alkylthio, C1-C10-alkyl which can carry from one to five halogen atoms and carries one of the following radicals: a five-membered heteroaromatic ring which contains from one to three nitrogen atoms and/or one sulfur or oxygen atom and which can carry from one to four halogen atoms and/or one or two of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy C1-C4-haloalkoxy, C1-C4-alkylthio and/or phenyl; C3-C12-cycloalkyl or C3-C12-cycloalkenyl, each of which can contain one oxygen or sulfur atom and can carry from one to five halogen atoms and/or one of the following radicals: C1-C4-alkyl, C1-C4--alkoxy, C1-C4-alkylthio, cyano, C1-C8-alkyl, -carbonyl, C1-C8-alkoxycarbonyl, phenyl, phenoxy or phenyl- carbonyl, where the phenyl radicals in turn can carry from one to five halogen atoms and/or from one to three of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and/or C1-C4-alkylthio; C3-C6-alkenyl or C3-C6-alkynyl, each of which can carry from one to five halogen atoms and/or one of the following radi-cals: C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio. Cyano, C1-C8-alkylcarbonyl , C1-C8-alkoxycarbonyl, phenyl, phenoxy or phenylcarbonyl, where the phenyl radicals in turn can carry from one to five halogen atoms and/or from one to three of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and/or C1-C4-alkylthio; a five- or six-membered heteroaromatic ring which contains from one to three nitrogen atoms and/or one sulfur or oxygen atom and which can carry from one to four halogen atoms and/ or one or two of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkyl-thio, phenyl, phenoxy or phenylcarbonyl, where the phenyl radicals in turn can carry from one to five halogen atoms and/or from one to three of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and/or C1-C4-alkylthio; phenyl or naphthyl, each of which can be substituted by one or more of the following radicals: halogen, nitro, cyano, hydroxyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenoxy, C1-C4-alkylthio, amino, C1-C4-alkylamino or C1-C4-dialkylamino;R4 and R5 form, together with the adjacent carbon atom, a 3- to 8-membered ring which can contain one oxygen or sulfur atom and can carry from one to three of the following radi-cals: C1-C4-alky1, halogen, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and/or C1-C4-alkylthio; is hydrogen, C1-C4-alkyl, C3-C6-alkenyl, C3-C6-alkynyl, C3-C8-cycloalkyl, C1-C4-haloalkyl, C1-C4-alkoxyalkyl, C1-C4-alkylthioalkyl phenyl or R5 is linked to R4 as indicated above to form a 3- to 8-membered ring; R6 is C1-C8-alkyl, C3-C6-alkenyl, C3-C6-alkynyl or C3-C8-cycloalkyl, it being possible for each of these radicals to be substituted one or more times by: halogen, nitro, cyano, C1-C4-alkoxy, C3-C6-alkenyloxy, C3-C6-alkynyloxy, C1-C4-alkyl thio, C1-C4-haloalkoxy, C1-C4-alkylcarbonyl, C1-C4-alkoxy carbonyl, C1-C4-alkylamino, di- C1-C4-alkylamino, phenyl, phenoxy or phenyl which is substituted one or more times, eg. From one to three times, by halogen, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy or C1-C4-alkylthio; phenyl or naphthyl, each of which can be substituted by one or more of the following radicals: halogen, nitro, cyano, hydroxyl, amino, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenoxy, C1-C4-alkylthio, C1-C4-alkylamino or C1-C4-dialkylamino; a five- or six-membered heteroaromatic ring which contains from one to three nitrogen atoms and/or one sulfur or oxygen atom and which can carry from one to four halogen atoms and/ or one or two of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkyl thio, phenyl, phenoxy or phenylcarbonyl, where the phenyl radicals in turn can carry from one to five halogen atoms and/or from one to three of the following radicals: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and/or C1-C4-alkylthio; Y is sulfur or oxygen or a single bond; Z is sulfur or oxygen; for the production of drugs.