Claims for Patent: 5,840,722

Summary for Patent: 5,840,722

Title:	Use of carboxylic acid derivatives as drugs
Abstract:	A method of inhibiting endothelin receptors by administering to a patient a compound of the formula I ##STR1##
Inventor(s):	Ernst Baumann, Uwe Josef Vogelbacher, Joachim Rheinheimer, Dagmar Klinge, Hartmut Riechers, Burkhard Kroger, Siegfried Bialojan, Claus Bollschweiler, Wolfgang Wernet, Liliane Unger, Manfred Raschack
Assignee:	Royalty Pharma Collection Trust
Application Number:	US08/718,377
Patent Claims:	1. A method of inhibiting endothelin receptors by administering to a patient a compound of the formula I ##STR16## where R is formyl, CO2 H 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 which, in each case, one methylene group is replaced by oxygen; 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 -C4 -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, 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 -C8 -alkenyl or C3 C6 -alkynyl, each of which 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 -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, C14 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy, CL-c4 -alkylthio, 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 -4 -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-membered membered ring which can contain one oxygen or sulfur atom and can carry from one to three of the following radicals: C1 -C4 -alkyl, halogen, C1 -4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy and/or C1 -C4 -akylthio; is hydrogen, C1 -C4 -alkyl, C3 --alkenyl, C3 -alkynyl, C3 -C8 -Cycloalkyl, C4 -C4 -haloalkyl, C4 -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 sufyl-alkyl, C3 --alkenyl, C3 --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 --alkynyloxy, C1 -C4 -alkyl-thio, C1 -C4 -haloalkoxy, C1 -C4 -alkylcarbonyl, C4 -alkoxy carbonyl, C1 -C4 -alkylamino , di-C1 -C4 -alkylamino, phenyl, phenoxy or phenyl which is substituted one or more times, e.g. from one to three times, by halogen, nitro, cyano, C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, 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.