Claims for Patent: 5,932,730

Summary for Patent: 5,932,730

Title:	Carboxylic acid derivatives, their preparation and use
Abstract:	Carboxylic acid derivatives ##STR1## where R-R6, X, Y and Z have the meanings stated in the description, and the preparation thereof, are described. The novel compounds are suitable for controlling diseases.
Inventor(s):	Hartmut Riechers, Dagmar Klinge, Wilhelm Amberg, Andreas Kling, Stefan Muller, Ernst Baumann, Joachim Rheinheimer, Uwe Josef Vogelbacher, Wolfgang Wernet, Liliane Unger, Manfred Raschack
Assignee:	Royalty Pharma Collection Trust
Application Number:	US08/809,699
Patent Claims:	1. A compound of the formula I ##STR16## where R is formyl, tetrazole, nitrile, a COOH group or a radical which can be hydrolyzed to COOH, and the other substituents have the following meanings:R2 hydrogen, hydroxyl, NH2, NH(C1 -C4 -alkyl), N(C1 -C4 -alkyl)2, halogen, C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy or C1 -C4 -alkylthio; R3 hydrogen, hydroxyl, NH2, NH(C1 -C4 -alkyl), N(C1 -C4 -alkyl)2, halogen, C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy, NH--O--C1 -C4 -alkyl, C1 -C4 -alkylthio or CR3 is linked to CR14 as indicated above to give a 5- or 6-membered ring; R4 and R5 , which can be identical or different, are phenyl or naphthyl, 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; orphenyl or naphthyl, which are connected together in the ortho position via a direct linkage, a methylene, ethylene or ethenylene group, an oxygen or sulfur atom or an SO2, NH or N-alkyl group; or C3 -C7 -cycloalkyl; R6 hydrogen, C1 -C8 -alkyl, C3 -C6 -alkenyl, C3 -C6 -alkynyl or C3 -C8 -cycloalkyl, where each of these radicals can be substituted one or more times by: halogen, nitro, cyano, C1 -C4 -alkoxy, C3 -C6 -alkenyloxy, C3 -C6 -alkynyloxy, C1 -C4 -alkylthio, C1 -C4 -haloalkoxy, C1 -C4 -alkylcarbonyl, C1 -C4 -alkoxycarbonyl, C3 -C8 -alkylcarbonylalkyl, C1 -C4 -alkylamino, di-C1 -C4 -alkylamino, phenyl or phenoxy which is substituted one or more 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, C1 -C4 -dialkylamino or dioxomethylene or dioxoethylene; a five or six-membered heteroaromatic moiety containing one to three nitrogen atoms and/or one sulfur or oxygen atom, which can carry 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, phenyl, phenoxy or phenylcarbonyl, it being possible for the phenyl radicals in turn to carry one to five halogen atoms and/or 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 sulfur or oxygen or a single bond; Z sulfur, oxygen, --SO-- or --SO2 --. 2. The compound of the formula I as defined in claim 1, wherein X is CR14 and R14 is hydrogen. 3. The compound of the formula I as defined in claim 2, wherein R is CO2 H. 4. The compound of the formula I as defined in claim 2, wherein R2 and R3 each is methoxy. 5. The compound of the formula I as defined in claim 2, wherein R4 and R5 each is phenyl. 6. The compound of the formula I as defined in claim 2, wherein R6 is C1 -C8 -alkyl. 7. The compound of the formula I as defined in claim 2, wherein Y is oxygen. 8. The compound of the formula I as defined in claim 2, wherein Z is oxygen or sulfur. 9. The compound of the formula I as defined in claim 8, wherein Z is oxygen. 10. The compound of the formula I as defined in claim 1, whereinX is CH, Y is oxygen, Z is oxygen, R is CO2 H, R2 is methoxy, R3 is methoxy, R4 is phenyl, R5 is phenyl, R6 is methyl, ethyl or iso-propyl. 11. The compound of the formula I as defined in claim 1, wherein R is tetrazole, nitrile or a group ##STR17## where R1 has the following meanings: a) hydrogen;b) succinylimidoxy; c) a five-membered heteroaromatic ring linked by a nitrogen atom, selected from the group consisting of: pyrrolyl, pyrazolyl, imidazolyl and triazolyl, which ring can carry one or two halogen atoms and or one or two of the following radicals: C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy or C1 -C4 -alkylthio; d) a radical ##STR18## where m is 0 or 1 and R7 and R8, which can be identical or different, have the following meanings:hydrogen, C1 -C8 -alkyl, C3 -C6 -alkenyl, C3 -C6 -alkynyl, C3 -C8 -cycloalkyl, where these alkyl, cycloalkyl, alkenyl and alkynyl groups can each carry one to five halogen atoms and/or one or two of the following groups: C1 -C4 -alkyl, C1 -C4 -alkoxy, C1 -C4 -alkylthio, C1 -C4 -haloalkoxy, C3 -C6 -alkenyloxy, C3 -C6 -alkenylthio, C3 -C6 -alkynyloxy or C3 -C6 -alkynylthio, C1 -C4 -alkylcarbonyl, C1 -C4 -alkoxycarbonyl, C3 -C6 -alkenylcarbonyl, C3 -C6 -alkynylcarbonyl, C3 -C6 -alkenyloxycarbonyl or C3 -C6 -alkynyloxycarbonyl, phenyl, which can be substituted one or more times by halogen, nitro, cyano, C3 -C6 -alkenylcarbonyl, C3 -C6 -alkynylcarbonyl, C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy or C1 -C4 -alkylthio, di-C1 -C4 -alkylamino, orR7 and R8 together form a C4 -C7 -alkylene chain which can be substituted by C1 -C4 -alkyl, and may contain a hetero atom selected from the group consisting of oxygen, sulfur and nitrogen, or R7 and R8 together form a CH2 --CH═CH--CH2 or CH═CH--(CH2)3 chain; e) a radical ##STR19## where k is 0, 1 and 2, p is 1, 2, 3 and 4, and R9 is C1 -C4 -alkyl, C1 -C4 -haloalkyl, C3 -C6 -alkenyl, C3 -C6 -alkynyl or phenyl, which can be substituted one or more times by halogen, nitro, cyano, C3 -C6 -alkenylcarbonyl, C3 -C6 -alkynylcarbonyl, C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy or C1 -C4 -alkylthio; f) a radical OR10, where R10 ishydrogen, the cation of an alkali metal or an alkaline earth metal or an environmentally compatible organic ammonium ion; C3 -C8 -cycloalkyl which may carry one to three C1 -C4 -alkyl groups; C1 -C8 -alkyl which may carry one to five halogen atoms and/ or one of the following radicals: C1 -C4 -alkoxy, C1 -C4 -alkylthio, cyano, C1 -C4 -alkylcarbonyl, C3 -C8 -cycloalkyl, C1 -C4 -alkoxycarbonyl, phenyl, phenoxy or phenylcarbonyl, where the aromatic radicals in turn may carry one to five halogen atoms and/or one to three of the following radicals: nitro, cyano, C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy and/or C1 -C4 -alkylthio; C1 -C8 -alkyl which may carry one to five halogen atoms and which carries one of the following radicals: a 5-membered heteroaromatic ring containing one to three nitrogen atoms or a nitrogen atom and an oxygen or sulfur atom, which may carry one to four halogen atoms and/or one or two of the following radicals: nitro, cyano, C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, phenyl, C1 -C4 -haloalkoxy and/or C1 -C4 -alkylthio; C2 -C6 -alkyl which carries one of the following radicals in position 2: C1 -C4 -alkoxyimino, C3 -C6 -alkynyloxyimino, C3 -C6 -haloalkenyloxyimino or benzyloxyimino; C3 -C6 -alkenyl or C3 -C6 -alkynyl which may carry one to five halogen atoms; phenyl which may carry one to five halogen atoms and/or one to three of the following radicals: nitro, cyano, C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy and/or C1 -C4 -alkylthio; a 5-membered heteroaromatic ring which is bonded via a nitrogen atom and containing one to three nitrogen atoms, which may carry one or two halogen atoms and or one or two of the following radicals: C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, phenyl, C1 -C4 -haloalkoxy and/or C1 -C4 -alkylthio; a radical ##STR20## where R1 and R12, which may be identical or different are: C1 -C8-alkyl, C3 -C6 -alkenyl, C3 -C6 -alkynyl, C3 -C8 -cycloalkyl, it being possible for these radicals to carry a C1 -C4 -alkoxy, C1 -C4 -alkylthio and/or phenyl which may carry one to five halogen atoms and/or one to three of the following radicals: nitro, cyano, C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy and/or C1 -C4 -alkylthio; phenyl which may carry one or more of the following radicals: halogen, nitro, cyano, C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy or C1 -C4 -alkylthio; or R11 and R12 together form a C3 -C12 -alkylene chain which may carry one to three C1 -C4 -alkyl groups and which may contain a hetero atom selected from the group consisting of nitrogen, oxygen and sulfur; g) a radical ##STR21## where R13 is C1 -C4 -alkyl, C3 -C6 -alkenyl, C3 -C6 -alkynyl, C3 -C8 -cycloalkyl, it being possible for these radicals to carry a C1 -C4 -alkoxy, C1 -C4 -alkylthio and/or a phenyl radical, orphenyl which may carry one or more of the following radicals: halogen, nitro, cyano, C1 -C4 -alkyl, C1 -C4 -haloalkyl, C1 -C4 -alkoxy, C1 -C4 -haloalkoxy or C1 -C4 -alkylthio.