Carboxylic acid derivatives, their preparation and use

Abstract

Carboxylic acid derivatives where R-R 6 , 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.

1. A compound of the formula I 
       
         
           
           
               
               
           
         
       
       where
 R is formyl, tetrazole, nitrile, a COOH group —CO 2 H or a radical which can be hydrolyzed to COOH, and the other substituents have the following meanings: —CO 2 H; 
 R 2  hydrogen, hydroxyl, NH 2 , NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, is C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or C 1 -C 4 -alkylthio; 
 X is CR 14 , where R 14  is hydrogen or C 1 -C 5 -alkyl; 
 R 3  hydrogen, hydroxyl, NH 2 , NH(C 1 -C 4 -alkyl), N(C 1 -C 4 -alkyl) 2 , halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, is C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, —NH—O—C 1 -C 4 -alkyl, or C 1 -C 4 -alkylthio or CR 3  is linked to CR 14  as indicated above to give a 5- or 6-membered ring; 
 R 4  and R 5 , 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, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, C 1 -C 4 -alkylthio, amino, C 1 -C 4 -alkylamino or and C 1 -C 4 -dialkylamino; or 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 SO 2 , NH or N-alkyl group; or a C 3 -C 7 -cycloalkyl group; 
 R 6  is hydrogen, or R 6  is C 1 -C 8 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl or C 3 -C 8 -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, C 1 -C 4 -alkoxy, C 3 -C 6 -alkenyloxy, C 3 -C 6 -alkynyloxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkoxy, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 3 -C 8 -alkylcarbonylalkyl, C 1 -C 4 -alkylamino, di-C 1 -C 4 -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, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or and C 1 -C 4 -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, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylamino, C 1 -C 4 -dialkylamino or, 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: C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, and C 1 -C 4 -haloalkoxy, C 1 -C 4 -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 one to three of the following radicals selected from the group consisting of: 
 
 C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy and/or C 1 -C 4 -alkylthio;, 
 Y is sulfur or, oxygen or a single bond; and 
 Z is sulfur, oxygen, —SO— or —SO 2 —. 
 
     
     
       2. The compound of the formula I as defined in  claim 1 , wherein X is CR 14  and R 14  is hydrogen. 
     
     
       3. The compound of the formula I as defined in  claim 2 , wherein R is CO 2 H. 
     
     
       4. The compound of the formula I as defined in  claim 2 , wherein R 2  and R 3  each is methoxy. 
     
     
       5. The compound of the formula I as defined in  claim 2 , wherein R 4  and R 5  each is phenyl. 
     
     
       6. The compound of the formula I as defined in  claim 2 , wherein R 6  is C 1 -C 8 -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 —CO 2 H,; 
 R 2  is methoxy,; 
 R 3  is methoxy,; 
 R 4  is phenyl,; 
 R 5  is phenyl,; and 
 R 6  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 R 1  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: C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or and C 1 -C 4 -alkylthio; 
 d) a radical 
 
       
         
           
           
               
               
           
         
          where m is 0 or 1 and R 7  and R 8 , which can be identical or different, have the following meanings:
 hydrogen, 
 C 1 -C 8 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 3 -C 8 -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: C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -haloalkoxy, C 3 -C 6 -alkenyloxy, C 3 -C 6 -alkenylthio, C 3 -C 6 -alkynyloxy or C 3 -C 6 -alkynylthio, C 1 -C 4 -alkylcarbonyl, C 1 -C 4 -alkoxycarbonyl, C 3 -C 6 -alkenylcarbonyl, C 3 -C 6 -alkynylcarbonyl, C 3 -C 6 -alkenyloxycarbonyl or and C 3 -C 6 -alkynyloxycarbonyl, 
 phenyl, which can be substituted by one or more times by substituents selected from the group consisting of: halogen, nitro, cyano, C 3 -C 6 -alkenylcarbonyl, C 3 -C 6 -alkynylcarbonyl, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or, C 1 -C 4 -alkylthio, and di-C 1 -C 4 -alkylamino, or
 R 7  and R 8  together form a C 4 -C 7 -alkylene chain which can be substituted by C 1 -C 4 -alkyl, and may contain a hetero atom selected from the group consisting of: oxygen, sulfur and nitrogen, or R 7  and R 8  together form a CH 2 —CH═CH—CH 2  or CH═CH—(CH 2 ) 3  chain; 
 
 
         e) a radical 
       
       
         
           
           
               
               
           
         
          where k is 0, 1 and 2, p is 1, 2, 3 and 4, and R 9  is C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl or phenyl, which can be substituted by one or more times by substituents selected from the group consisting of: halogen, nitro, cyano, C 3 -C 6 -alkenylcarbonyl, C 3 -C 6 -alkynylcarbonyl, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or and C 1 -C 4 -alkylthio; 
         f) a radical OR 10 , where R 10  is
 hydrogen, the cation of an alkali metal or an alkaline earth metal or an environmentally compatible organic ammonium ion; 
 C 3 -C 8 -cycloalkyl which may carry one to three C 1 -C 4 -alkyl groups; 
 C 1 -C 8 -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: C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, cyano, C 1 -C 4 -alkylcarbonyl, C 3 -C 8 -cycloalkyl, C 1 -C 4 -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, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy and/or C 1 -C 4 -alkylthio; 
 C 1 -C 8 -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, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, phenyl, C 1 -C 4 -haloalkoxy and/or C 1 -C 4 -alkylthio; 
 C 2 -C 6 -alkyl which carries one of the following radicals in position 2: C 1 -C 4 -alkoxyimino, C 3 -C 6 -alkynyloxyimino, C 3 -C 6 -haloalkenyloxyimino or benzyloxyimino; 
 C 3 -C 6 -alkenyl or C 3 -C 6 -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, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy and/or C 1 -C 4 -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: C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, phenyl, C 1 -C 4 -haloalkoxy and/or C 1 -C 4 -alkylthio; 
 a radical 
 
       
       
         
           
           
               
               
           
         
         
            where R 1  R 11  and R 12 , which may be identical or different are:
 C 1 -C 8 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, it being possible for these radicals to carry a one or more substituents selected from the group consisting of: C 1 -C 4 -alkoxy, C 1 -C 4 -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, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy and/or C 1 -C 4 alkylthio; 
 phenyl which may carry one or more of the following radicals selected from the group consisting of: halogen, nitro, cyano, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or and C 1 -C 4 -alkylthio; or R 11  and R 12  together form a C 3 -C 12 -alkylene chain which may carry one to three C 1 -C 4 -alkyl groups and which may contain a hetero atom selected from the group consisting of: nitrogen, oxygen and sulfur; 
 
         
         g) a radical 
       
       
         
           
           
               
               
           
         
          where R 13  is
 C 1 -C 4 -alkyl, C 3 -C 6 -alkenyl, C 3 -C 6 -alkynyl, C 3 -C 8 -cycloalkyl, it being possible for these radicals to carry one or more substituents selected from the group consisting of: a C 1 -C 4 -alkoxy, a C 1 -C 4 -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, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy or and C 1 -C 4 -alkylthio. 
 
       
     
     
       12. The compound of the formula I as defined in claim 1, wherein
 R is —CO 2 H or a radical which can be hydrolyzed to —CO 2 H;   R 4  is phenyl; and   R 5  is phenyl.   
     
     
       13. The compound of the formula as defined in claim 1, wherein
 R is formyl, —CO 2 H or a radical which can be hydrolyzed to —CO 2 H;   R 2  is C 1 -C 4 -alkoxy;   X is CR 14 , where R 14  is hydrogen or C 1 -C 5 -alkyl;   R 3  is C 1 -C 4 -alkoxy or C 1 -C 4 -alkylthio;   R 4  and R 5  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, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -alkylthio; or
 phenyl which are connected together in the ortho positions by a direct linkage, methylene, ethylene, ethenylene, oxygen, sulfur, —SO 2 —, —NH— or N-alkyl group; or 
 C 3 -C 7 -cycloalkyl; 
   R 6  is C 1 -C 8 -alkyl, C 3 -C 6 -alkenyl or C 3 -C 8 -cycloalkyl, where each of these can be substituted by one or more substituents selected from the group consisting of: halogen, hydroxyl, nitro, cyano, C 1 -C 4 -alkoxy, C 3 -C 6 -alkenyloxy and C 1 -C 4 -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, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -haloalkoxy, phenoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylamino and C 1 -C 4 -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: C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -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: C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -alkylthio; 
   Y is sulfur, oxygen or a single bond; and   Z is sulfur, oxygen, SO or SO 2 .   
     
     
       14. The compound of the formula I as defined in claim 1, wherein
 R is —CO 2 H or a radical which can be hydrolyzed to —CO 2 H;   R 2  is C 1 -C 4 -alkoxy;   X is CR 14 , where R 14  is hydrogen;   R 3  is C 1 -C 4 -alkoxy;   R 4  and R 5  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, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -alkylthio;   R 6  is C 1 -C 8 -alkyl, which can by substituted by one or more substituents selected from the group consisting of: halogen, hydroxyl, nitro, cyano, C 1 -C 4 -alkoxy, C 3 -C 6 -alkenyloxy and C 1 -C 4 -alkylthio;   Y is oxygen; and   Z is oxygen.   
     
     
       15. The compound of the formula I as defined in claim 14, where R is —CO 2 H. 
     
     
       16. The compound of the formula I as defined in claim 15, where R 4  and R 5  are each phenyl. 
     
     
       17. The compound of the formula I as defined in claim 1, wherein
 R is —CO 2 H;   R 2  is C 1 -C 4 -alkoxy;   X is CR 14 , where R 14  is hydrogen or C 1 -C 5 -alkyl;   R 3  is C 1 -C 4 -alkoxy;   R 4  and R 5  are phenyl which can be substituted by one or more halogen atoms;   R 6  is C 1 -C 8 -alkyl or C 3 -C 8 -cycloalkyl, where each of these can be substituted one or more times by phenyl, or phenyl;   Y is oxygen; and   Z is sulfur or oxygen.   
     
     
       18. The compound of the formula I as defined in claim 1, wherein
 R is —CO 2 H or a radical which can be hydrolyzed to CO 2 H;   R 2  is C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkoxy;   X is CR 14 , where R 14  is hydrogen or C 1 -C 5 -alkyl;   R 3  is C 1 -C 4 -alkoxy or C 1 -C 4 -haloalkoxy;   R 4  and R 5  are phenyl, which can be substituted by one or more of the following selected from the group consisting of: halogen, nitro, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylamino and C 1 -C 4 -dialkylamino;   R 6  is hydrogen, or R 6  is C 1 -C 8 -alkyl or C 3 -C 8 -cycloalkyl, where each of these can be substituted by one or more substituents selected from the group consisting of: halogen, hydroxyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio and phenyl which is substituted by one or more substituents selected from the group consisting of: halogen, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, C 1 -C 4 -alkoxy and C 1 -C 4 -alkylthio; or
 phenyl which can be substituted by one or more of the following selected from the group consisting of: halogen, nitro, hydroxyl, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -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.   
     
     
       19. The compound of claim 18, wherein
 R is —CO 2 H, —COOCH 3 , —COON(CH 3 ) 2 , —COOCH 2 C≡CH, —COOC 2 H 5 , —COON═C(CH 3 ) 2 , —COONH-phenyl, —COOCH═CH 2  or —CONH—SO—C 6 H 5 ;   R 2  is —OCF 3 , —OCH 3  or —OCH 2 CH 3 ;   X is CR 14 , where R 14  is hydrogen-;   R 3  is —OCF 3 , —OCH 3  or —OCH 2 CH 3 ;   R 4  and R 5  are phenyl, which can be substituted by one or more groups selected from the group consisting of: —F, —Cl, —Br, —CH 3 , —CH 2 CH 3 , —CF 3 , —OCH 3 , —NO 2  and —N(CH 3 ) 2 ;   R 6  is —H, —CH 3 , —CH 2 CH 3 , —CH 2 CH 2 CH 3 , —C(CH 3 ) 3 , —CH 2 CH(CH 3 ) 2 , cyclopropyl, —CH 2 CH 2 CH 2 CH(CH 3 ) 2 , —CH 2 —CH 2 —S—CH 3 , —CH 2 CH 2 OH, phenyl, 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-NO 2 -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.   
     
     
       20. The compound of claim 19, wherein R 4  and R 5  are each phenyl.