Claims for Patent: RE42462

Summary for Patent: RE42462

Title:	Carboxylic acid derivatives, their preparation and use
Abstract:	Carboxylic acid derivatives 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:	US12/481,594
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent RE42462
Patent Claims:	1. A compound of the formula I where R is formyl, tetrazole, nitrile, a COOH group —CO2H or a radical which can be hydrolyzed to COOH, and the other substituents have the following meanings: —CO2H; R2 is hydrogen, hydroxyl, —NH2, —NH(C1-C4-alkyl), —N(C1-C4-alkyl)2, halogen, C1-C4-alkyl, or C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy or C1-C4-alkylthio; X is CR14, where R14 is hydrogen or C1-C5-alkyl; R3 is hydrogen, hydroxyl, —NH2, —NH(C1-C4-alkyl), —N(C1-C4-alkyl)2, halogen, C1-C4-alkyl, or 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 selected from the group consisting of: 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 and C1-C4-dialkylamino; or R4 and R5 are phenyl 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 a C3-C7-cycloalkyl group; R6 is hydrogen, or R6 is C1-C8-alkyl, C3-C6-alkenyl, C3-C6-alkynyl or C3-C8-cycloalkyl, where each of these radicals can be substituted by one or more times by substituents selected from the group consisting of: 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 and phenoxy which phenyl or phenoxy is substituted by one or more times by substituents selected from the group consisting of: halogen, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy or and C1-C4-alkylthio; or phenyl or naphthyl, each of which can be substituted by one or more of the following radicals selected from the group consisting of: 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 , dioxomethylene or and dioxoethylene; or a five or six-membered heteroaromatic moiety containing (i) one to three nitrogen atoms, and/or one sulfur or oxygen atom (ii) one sulfur atom, (iii) one oxygen atom, (iv) one to three nitrogen atoms and one sulfur atom, or (v) one to three nitrogen atoms and one oxygen atom, which heteroaromatic moiety can carry one or more substituents selected from the group consisting of: one to four halogen atoms and/or, and one or two of the following radicals selected from the group consisting of: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, C1-C4-alkylthio, phenyl, phenoxy or and phenylcarbonyl, it being possible for the phenyl radicals in turn to carry one or more substituents selected from the group consisting of: one to five halogen atoms and/or, and one to three of the following radicals selected from the group consisting of: 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; and Z is 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 CO2H. 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, wherein X is CH, Y is oxygen, Z is oxygen, R is CO2H, 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 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 more substituents selected from the group consisting of: one or two halogen atoms and or, and one or two of the following radicals selected from the group consisting of: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy or and C1-C4-alkylthio; d) a radical 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 or more substituents selected from the group consisting of: one to five halogen atoms and/or, and one or two of the following groups selected from the group consisting of: 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 and C3-C6-alkynyloxycarbonyl,; phenyl, which can be substituted by one or more times by substituents selected from the group consisting of: 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, and di-C1-C4-alkylamino, or R7 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 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 by one or more times by substituents selected from the group consisting of: halogen, nitro, cyano, C3-C6-alkenylcarbonyl, C3-C6-alkynylcarbonyl, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy or and C1-C4-alkylthio; f) a radical OR10, where R10 is hydrogen, 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 or more substituents selected from the group consisting of: one to five halogen atoms and/or, and one of the following radicals selected from the group consisting of: C1-C4-alkoxy, C1-C4-alkylthio, cyano, C1-C4-alkylcarbonyl, C3-C8-cycloalkyl, C1-C4-alkoxycarbonyl, phenyl, phenoxy or and phenylcarbonyl, where the aromatic radicals substituents in turn may carry one or more substituents selected from the group consisting of: one to five halogen atoms and/or, and one to three of the following radicals selected from the group consisting of: 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 selected from the group consisting of: a 5-membered heteroaromatic ring containing one to three nitrogen atoms or, a nitrogen atom and an oxygen or and a nitrogen atom and a sulfur atom, which may carry one or more substituents selected from the group consisting of: one to four halogen atoms and/or, and one or two of the following radicals selected from the group consisting of: 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 or more substituents selected from the group consisting of: one to five halogen atoms and/or, and one to three of the following radicals selected from the group consisting of: 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 more substituents selected from the group consisting of: one or two halogen atoms, and or one or two of the following radicals selected from the group consisting of: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, phenyl, C1-C4-haloalkoxy and/or C1-C4-alkylthio; a radical where R1 R11 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 one or more substituents selected from the group consisting of: C1-C4-alkoxy, C1-C4-alkylthio, and/or phenyl, which may carry one or more substituents selected from the group consisting of: one to five halogen atoms and/or, and one to three of the following radicals selected from the group consisting of: nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy and/or C1-C4alkylthio; phenyl which may carry one or more of the following radicals selected from the group consisting of: halogen, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy or and 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: a nitrogen, oxygen and sulfur; g) a radical where R13 is C1-C4-alkyl, C3-C6-alkenyl, C3-C6-alkynyl, C3-C8-cycloalkyl, it being possible for these radicals to carry one or more substituents selected from the group consisting of: a C1-C4-alkoxy, a C1-C4-alkylthio and/or a phenyl radical, and a phenyl; or phenyl which may carry one or more of the following radicals selected from the group consisting of: halogen, nitro, cyano, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy or and C1-C4-alkylthio. 12. The compound of the formula I as defined in claim 1, wherein R is —CO2H or a radical which can be hydrolyzed to —CO2H; R4 is phenyl; and R5 is phenyl. 13. The compound of the formula I as defined in claim 12, wherein X is CH; Y is oxygen; Z is oxygen; R is —CO2H; R2 is C1-C4-alkyl; R3 is C1-C4-alkyl; and R6 is C1-C8-alkyl. 14. The compound of the formula I as defined in claim 13, wherein R2 is methyl; and R3 is methyl. 15. The compound of the formula as defined in claim 1, wherein R is formyl, —CO2H or a radical which can be hydrolyzed to —CO2H; R2 is C1-C4-alkyl; X is CR14, where R14 is hydrogen or C1-C5-alkyl; R3 is C1-C4-alkyl; R4 and R5 which can be identical or different, are phenyl, which can be substituted by one or more of the following selected from the group consisting of: halogen, nitro, hydroxyl, C1-C4-alkyl, C1-C4-alkoxy and C1-C4-alkylthio; or phenyl which are connected together in the ortho positions by a direct linkage, methylene, ethylene, ethenylene, oxygen, sulfur, —SO2—, —NH— or N-alkyl group; or C3-C7-cycloalkyl; R6 is C1-C8-alkyl, C3-C6-alkenyl or C3-C8-cycloalkyl, where each of these can be substituted by one or more substituents selected from the group consisting of: halogen, hydroxyl, nitro, cyano, C1-C4-alkoxy, C3-C6-alkenyloxy and C1-C4-alkylthio; or phenyl or naphthyl, each of which can be substituted by one or more of the following selected from the group consisting of: halogen, nitro, cyano, hydroxyl, amino, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, phenoxy, C1-C4-alkylthio, C1-C4-alkylamino and C1-C4-dialkylamino; or a five- or six-membered heteroaromatic moiety containing (i) a nitrogen atom, (ii) a sulfur atom, (iii) an oxygen atom, (iv) a nitrogen atom and a sulfur atom, or (v) a nitrogen atom and an oxygen atom, which heteroaromatic moiety can carry one or more substituents selected from the group consisting of: one to four halogen atoms, and one or two of the following selected from the group consisting of: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-alkylthio, phenyl, phenoxy and phenylcarbonyl, it being possible for the phenyl in turn to carry one or more substituents selected from the group consisting of: one to five halogen atoms, and one to three of the following selected from the group consisting of: C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-alkylthio; Y is sulfur, oxygen or a single bond; and Z is sulfur, oxygen, SO or SO2. 16. The compound of the formula I as defined in claim 15, wherein R is —CO2H; R2 is C1-C4-alkyl; X is CR14, where R14 is hydrogen; R3 is C1-C4-alkyl; R4 and R5 which can be identical or different, are phenyl, which can be substituted by one or more of the following selected from the group consisting of: halogen, nitro, hydroxyl, C1-C4-alkyl, C1-C4-alkoxy and C1-C4-alkylthio; R6 is C1-C8-alkyl, which can by substituted by one or more substituents selected from the group consisting of: halogen, hydroxyl, nitro, cyano, C1-C4-alkoxy, C3-C6-alkenyloxy and C1-C4-alkylthio; Y is oxygen; and Z is oxygen. 17. The compound of the formula I as defined in claim 16, where R4 and R5 are each phenyl. 18. The compound of the formula I as defined in claim 1, wherein R is —CO2H or a radical which can be hydrolyzed to —CO2H; R2 is C1-C4-alkyl; X is CR14, where R14 is hydrogen; R3 is C1-C4-alkyl; R4 and R5 which can be identical or different, are phenyl, which can be substituted by one or more of the following selected from the group consisting of: halogen, nitro, hydroxyl, C1-C4-alkyl, C1-C4-alkoxy and C1-C4-alkylthio; R6 is C1-C8-alkyl, which can be substituted by one or more substitutents selected from the group consisting of: halogen, hydroxyl, nitro, cyano, C1-C4-alkoxy, C3-C6-alkenyloxy and C1-C4-alkylthio; Y is oxygen; and Z is oxygen. 19. The compound of the formula I as defined in claim 18, where R4 and R5 are each phenyl. 20. The compound of the formula I as defined in claim 1, wherein R is —CO2H; R2 is C1-C4-alkyl; X is CR14, where R14 is hydrogen or C1-C5-alkyl; R3 is C1-C4-alkyl; R4 and R5 are phenyl which can be substituted by one or more halogen atoms; R6 is C1-C8-alkyl or C3-C8-cycloalkyl, where each of these can be substituted one or more times by phenyl, or phenyl; Y is oxygen; and Z is sulfor or oxygen. 21. The compound of the formula I as defined in claim 1, wherein R is —CO2H or a radical which can be hydrolyzed to CO2H; R2 is halogen, C1-C4-alkyl or C1-C4-haloalkyl; X is CR14, where R14 is hydrogen or C1-C5-alkyl; R3 is halogen, C1-C4-alkyl or C1-C4-haloalkyl; R4 and R5 are phenyl, which can be substituted by one or more of the following selected from the group consisting of: halogen, nitro, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy, C1-C4-alkylamino and C1-C4-dialkylamino; R6 is hydrogen, or R6 is C1-C8-alkyl or C3-C8-cycloalkyl, where each of these can be substituted by one or more substituents selected from the group consisting of: halogen, hydroxyl, C1-C4-alkoxy, C1-C4-alkylthio and phenyl which is substituted by one or more substituents selected from the group consisting of: halogen, C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-alkoxy and C1-C4-alkylthio; or phenyl which can be substituted by one or more of the following selected from the group consisting of: halogen, nitro, hydroxyl, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylthio and dioxomethylene; or a five or six-membered heteroaromatic moiety containing (i) one to three nitrogen atoms, (ii) one sulfur atom, (iii) one oxygen atom, (iv) one to three nitrogen atoms and one sulfur atom, or (v) one to three nitrogen atoms and one oxygen atom which heteroaromatic moiety can carry one to four halogen atoms; Y is sulfur or oxygen; and Z is sulfur or oxygen. 22. The compound of claim 21, wherein R is —CO2H, —COOCH3, —COON(CH3)2, —COOCH2C≡CH, —COOC2H5, —COON═C(CH3)2, —COONH-phenyl, —COOCH═CH2 or —CONH—SO—C6H5; R2 is —Cl, —CH3, —CH2CH3 or —CF3; X is CR14, where R14 is hydrogen; R3 is —Cl, —CH3, —CH2CH3 or —CF3; R4 and R5 are phenyl, which can be substituted by one or more groups selected from the group consisting of: —F, —Cl, —Br, —CH3, —CH2CH3, —CF3, —OCH3, —NO2 and —N(CH3)2; R6 is —H, —CH3, —CH2CH3, —CH2CH2CH3, —C(CH3)3, —CH2CH(CH3)2, cyclopropyl, —CH2CH2CH2CH(CH3)2, —CH2—CH2—S—CH3, —CH2CH2OH, phenyl, trifluoroethyl, p-isopropyl-phenyl, p-methyl-S-phenyl, p-methyl-O-phenyl, m-ethyl-phenyl, o-methyl-phenyl, o-Cl-phenyl, m-Br-phenyl, p-F-phenyl, p-methyl-phenyl, m-NO2-phenyl, o-HO-phenyl, 3,4-dimethoxy-phenyl, 3,4-dioxomethylene-phenyl, 3,4,5-trimethoxy-phenyl, benzyl, o-Cl-benzyl, m-Br-benzyl, p-F-benzyl, o-methyl-benzyl, m-ethyl-benzyl or p-isopropyl-benzyl; Y is sulfur or oxygen; and Z is sulfur or oxygen. 23. The compound of claim 22, wherein R4 and R5 are each phenyl. 24. A compound of the formula I: where R is —CO2H; R2 is C1-C4-alkyl; X is CR14, where R14 is hydrogen; R3 is C1-C4-alkyl; R4 and R5 which can be identical or different, are phenyl, which can be substituted by one or more of the following selected from the group consisting of: halogen, nitro, hydroxyl, C1-C4-alkyl, C1-C4-alkoxy and C1-C4-alkylthio; R6 is a C1-C8-alkyl, which can be substituted by one or more substituents selected from the group consisting of: halogen, hydroxyl, nitro, cyano, C1-C4-alkoxy, C3-C6-alkenyloxy and C1-C4-alkylthio; Y is oxygen; and Z is oxygen. 25. The compound of the formula I as defined in claim 24, wherein R4 and R5 are each phenyl.