Tetrhydropyridoindole Derivatives

Abstract

The invention relates to tetrahydropyridoindole derivatives and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions comprising one or more of those compounds and methods of treatment comprising administration of said compounds.

1 . A compound of Formula (I) 
     
       
         
         
             
             
         
       
       wherein 
       R 1 , R 2 , R 3  and R 4  independently represent hydrogen, C 1 -C 5 -alkyl, C 1 -C 5 -alkoxy, halogen, nitro, cyano or formyl; and 
       R 5  represents C 1 -C 5 -alkyl-carbonyl, C 2 -C 5 -alkenyl-carbonyl, C 1 -C 5 -alkyl-carbamoyl, aryl-C 1 -C 5 -alkyl, aryl-carbonyl, aryl-C 1 -C 5 -alkyl-carbonyl, aryl-C 1 -C 5 -alkoxy-carbonyl, aryl-carbamoyl, aryl-thiocarbamoyl, aryl-C 1 -C 5 -alkyl-carbamoyl, aryl-C 1 -C 5 -alkyl-thiocarbamoyl, cycloalkyl-carbonyl, cycloalkyl-C 1 -C 5 -alkyl-carbonyl, cycloalkyl-C 1 -C 5 -alkoxy-carbonyl, cycloalkyl-carbamoyl, heteroaryl-carbonyl, heteroaryl-C 1 -C 5 -alkyl-carbonyl or heteroaryl-C 1 -C 5 -alkoxy-carbonyl; or a salt of the compound. 
     
   
   
       2 . The compound according to  claim 1 , wherein
 R 1 , R 2 , R 3  and R 4  independently represent hydrogen, C 1 -C 5 -alkyl, C 1 -C 5 -alkoxy, halogen, nitro, cyano or formyl; and   R 5  represents C 1 -C 5 -alkyl-carbonyl, C 2 -C 5 -alkenyl-carbonyl, C 1 -C 5 -alkyl-carbamoyl, aryl-carbonyl, aryl-C 1 -C 5 -alkyl-carbonyl, aryl-C 1 -C 5 -alkoxy-carbonyl, aryl-carbamoyl, cycloalkyl-carbonyl, cycloalkyl-C 1 -C 5 -alkyl-carbonyl, cycloalkyl-C 1 -C 5 -alkoxy-carbonyl, heteroaryl-carbonyl, heteroaryl-C 1 -C 5 -alkyl-carbonyl or heteroaryl-C 1 -C 5 -alkoxy-carbonyl; or a salt of the compound.   
   
   
       3 . The compound according to  claim 1 , wherein
 R 1 , R 2 , R 3  and R 4  independently represent hydrogen, C 1 -C 5 -alkyl, C 1 -C 5 -alkoxy or halogen; and   R 5  represents C 1 -C 5 -alkyl-carbonyl, C 2 -C 5 -alkenyl-carbonyl, C 1 -C 5 -alkyl-carbamoyl, aryl-carbonyl, aryl-C 1 -C 5 -alkyl-carbonyl, aryl-C 1 -C 5 -alkoxy-carbonyl, aryl-carbamoyl, aryl-thiocarbamoyl, aryl-C 1 -C 5 -alkyl-carbamoyl, aryl-C 1 -C 5 -alkyl-thiocarbamoyl, cycloalkyl-carbonyl, cycloalkyl-C 1 -C 5 -alkyl-carbonyl, cycloalkyl-carbamoyl or heteroaryl-carbonyl; or a salt of the compound.   
   
   
       4 . The compound according to any one of  claims 1 - 3 , wherein R 1 , R 2 , R 3  and R 4  represent hydrogen, or a salt of the compound. 
   
   
       5 . The compound according to  claim 1  or  2 , wherein R 1 , R 2 , R 3  and R 4  independently represent C 1 -C 5 -alkyl, C 1 -C 3 -alkoxy, halogen, nitro, cyano or formyl, or a salt of the compound. 
   
   
       6 . The compound according to any one of  claims 1 - 3 , wherein one or two substituents selected from R 1 , R 2 , R 3  and R 4  independently represent methyl, trifluoromethyl, methoxy, fluoro, chloro or bromo, or a salt of the compound. 
   
   
       7 . The compound according to  claim 1 , wherein R 5  is 2 cyclohexyl-2-phenyl-acetyl; 2-naphthalen-1-yl-acetyl; 2-naphthalen-2-yl-acetyl; 3-cyclopentyl-propionyl; 3-phenyl-propionyl; acetyl; diphenylacetyl; hexanoyl; (E)-but-2-enoyl; 9H-fluoren-9-ylmethoxycarbonyl; benzyloxycarbonyl; phenylacetyl; ethylcarbamoyl; 2-bromo-3-methyl-benzoyl; 2-bromo-5-methyl-benzoyl; 2-methoxy-benzoyl; 3,4,5-trimethoxy-benzoyl; 3,5-bis-trifluoromethyl-benzoyl; 3,5-dimethoxy-benzoyl; 3-chloro-benzoyl; 4-bromo-benzoyl; 4-chloro-benzoyl; 4-methoxy-benzoyl; 4-tert.-butyl-benzoyl; 4-trifluoromethoxy-benzoyl; 4-trifluoromethyl-benzoyl; benzoyl; phenylcarbamoyl; 4′-ethyl-biphenyl-4-carbonyl; biphenyl-2-carbonyl; biphenyl-4-carbonyl; 2-methoxy-naphthalene-1-carbonyl; 4-methoxy-naphthalene-1-carbonyl; 2-ethoxy-naphthalene-1-carbonyl; naphthalene-1-carbonyl; cyclohexane-carbonyl; cyclopropane-carbonyl; pyridine-3-carbonyl; 2-chloro-6-methyl-pyridine-4-carbonyl; pyridine-4-carbonyl; furan-2-carbonyl; furan-3-carbonyl; 2-methyl-furan-3-carbonyl; 3-methyl-furan-2-carbonyl; 5-bromo-furan-2-carbonyl; pyrazine-2-carbonyl, benzo[b]thiophene-2-carbonyl; 5-chloro-thiophene-2-carbonyl; 3-methyl-thiophene-2-carbonyl; 5-methyl-thiophene-2-carbonyl; thiophene-2-carbonyl; or thiophene-3-carbonyl, or a salt of the compound. 
   
   
       8 . The compound according to  claim 1 , wherein
 R 1 , R 2 , R 3  and R 4  independently represent hydrogen, C 1 -C 5 -alkyl, C 1 -C 3 -alkoxy or halogen; and   R 5  represents C 1 -C 5 -alkyl-carbonyl; C 1 -C 5 -alkyl-carbamoyl; C 2 -C 5 -alkenyl-carbonyl; C 3 -C 6 -cycloalkyl-carbonyl; C 3 -C 6 -cycloalkyl-C 1 -C 3 -alkyl-carbonyl; C 3 -C 6 -cycloalkyl-carbamoyl; C 3 -C 6 -cycloalkyl-thiocarbamoyl; phenyl-carbonyl or phenyl-C 1 -C 3 -alkyl-carbonyl, wherein the phenyl moiety of these two groups may be mono-, di-, tri- or tetra-substituted by substituents independently selected from C 1 -C 4 -alkyl, C 1 -C 3 -alkoxy, halogen, trifluoromethyl and trifluoromethoxy, mono-substituted by C 3 -C 6 -cycloalkyl, or mono-substituted by a phenyl group which in turn may be substituted by a C 1 -C 3 -alkyl or C 1 -C 3 -alkoxy group; phenyl-C 1 -C 3 -alkoxy-carbonyl; phenyl-carbamoyl or phenyl-thiocarbamoyl, wherein these two groups are optionally independently mono- or poly-substituted by C 1 -C 5 -alkyl and/or halogen; phenyl-C 1 -C 3 -alkyl-carbamoyl; phenyl-C 1 -C 3 -alkyl-thiocarbamoyl; biphenyl-carbamoyl; naphthyl-carbonyl, naphthyl-C 1 -C 3 -alkyl-carbonyl or naphthyl-carbamoyl wherein the naphthyl moieties of these three groups are optionally mono- or poly-substituted by substituents independently selected from C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy and halogen; fluorenyl-carbonyl, optionally substituted by oxo; fluorenyl-C 1 -C 3 -alkoxy-carbonyl; or five- to nine-membered heteroaryl-carbonyl groups containing one to three heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein said groups may be substituted by one or two groups independently selected from C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy, halogen and trifluoromethyl; or a salt of the compound.   
   
   
       9 . The compound according to  claim 1  or  2 , wherein
 R 1 , R 2 , R 3  and R 4  independently represent hydrogen, C 1 -C 5 -alkyl, C 1 -C 3 -alkoxy or halogen; and   R 5  represents C 1 -C 5 -alkyl-carbonyl; C 2 -C 5 -alkenyl-carbonyl; C 3 -C 6 -cycloalkyl-carbonyl; C 3 -C 6 -cycloalkyl-C 1 -C 3 -alkyl-carbonyl; C 3 -C 6 -cycloalkyl-C 1 -C 3 -alkoxy-carbonyl; phenyl-carbonyl or phenyl-C 1 -C 3 -alkyl-carbonyl, wherein the phenyl moiety of said groups may be independently mono-, di- or tri-substituted by C 1 -C 4 -alkyl, C 1 -C 3 -alkoxy, halogen, trifluoromethyl or trifluoromethoxy, or mono-substituted by a phenyl group which in turn may be substituted by a C 1 -C 3 -alkyl or C 1 -C 3 -alkoxy group; naphthyl-carbonyl; fluorenyl-C 1 -C 3 -alkoxy-carbonyl; or five- or six-membered heteroaryl-carbonyl groups containing one to three heteroatoms independently selected from oxygen, nitrogen and sulfur, wherein said groups may be substituted by one or two groups independently selected from C 1 -C 3 -alkyl, C 1 -C 3 -alkoxy, halogen and trifluoromethyl; or a salt of the compound.   
   
   
       10 . The compound according to  claim 1 , wherein the compound is:
 (2-benzyloxycarbonyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-9H-fluoren-9-ylmethoxycarbonyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-acetyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-phenylacetyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   [2-(3,4,5-trimethoxy-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   (2-cyclohexanecarbonyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   [2-(4-methoxy-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(furan-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   (2-cyclopropanecarbonyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   [2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-methoxy-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-trifluoromethyl-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3,5-bis-trifluoromethyl-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3-cyclopentyl-propionyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3-phenyl-propionyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(biphenyl-4-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-tert.-butyl-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-trifluoromethoxy-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-((E)-but-2-enoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-chloro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3,5-dimethoxy-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   (2-diphenylacetyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-hexanoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   [2-(3-chloro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-bromo-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(pyridine-3-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   (2-benzoyl-8-methoxy-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-7-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-8-bromo-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-6-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   [2-(pyrazine-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-bromo-3-methyl-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4′-ethyl-biphenyl-4-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-bromo-5-methyl-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-chloro-6-methyl-pyridine-4-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(biphenyl-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(5-bromo-furan-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3-methyl-furan-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-methyl-furan-3-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(benzo[b]thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(5-chloro-thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(furan-3-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-naphthalen-2-yl-acetyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(thiophene-3-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-naphthalen-1-yl-acetyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2 (2 cyclohexyl-2-phenyl-acetyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   (2-phenylcarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-ethylcarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   [2-(2-ethoxy-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3-methyl-thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(5-methyl-thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid; or   [2-(pyridine-4-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid   
     or a salt of the compound. 
   
   
       11 . The compound according to  claim 10 , wherein the compound is:
 [[2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3-chloro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4′-ethyl-biphenyl-4-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-bromo-3-methyl-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   (2-benzoyl-8-bromo-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   [2-(4-bromo-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid; or   [2-(furan-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   
     or a salt of the compound. 
   
   
       12 . The compound according to  claim 1 , wherein the compound is:
 5-carboxymethyl-7-chloro-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester;   5-carboxymethyl-8-chloro-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester;   5-carboxymethyl-6-chloro-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester;   5-carboxymethyl-7-methyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester;   5-carboxymethyl-8-methyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester;   8-bromo-5-carboxymethyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester;   5-carboxymethyl-8-fluoro-1,3,4,5-tetrahydro-pyrido[4,3-b]indole-2-carboxylic acid tert-butyl ester;   [7-chloro-2-(3-chloro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-chloro-2-(3-chloro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [6-chloro-2-(3-chloro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3-chloro-benzoyl)-7-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3-chloro-benzoyl)-8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-bromo-2-(3-chloro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3-chloro-benzoyl)-8-fluoro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-chloro-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [6-chloro-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-bromo-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-fluoro-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [7-chloro-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [7-methyl-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-methyl-2-(thiophene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-fluoro-2-(2-methoxy-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-fluoro-2-(4-methoxy-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-chloro-2-(2-methoxy-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-chloro-2-(4-methoxy-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-methoxy-naphthalene-1-carbonyl)-8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-methoxy-naphthalene-1-carbonyl)-8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   2-(2-methoxy-naphthalene-1-carbonyl)-7-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-ethoxy-naphthalene-1-carbonyl)-8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-ethoxy-naphthalene-1-carbonyl)-7-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-methoxy-naphthalene-1-carbonyl)-7-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-fluoro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3-fluoro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3,5-difluoro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3,4,5-trifluoro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2,3,4,5-tetrafluoro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   (2-benzoyl-8-fluoro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-6-chloro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-8-isopropyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-8-chloro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-7,8-dichloro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-8-trifluoromethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-8-tert-butyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-7-chloro-8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-7,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzoyl-7-fluoro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   [7-chloro-2-(2-naphthalen-1-yl-acetyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-chloro-2-(2-naphthalen-1-yl-acetyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [7-methyl-2-(2-naphthalen-1-yl-acetyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-bromo-2-(2-naphthalen-1-yl-acetyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4′-ethyl-biphenyl-4-carbonyl)-7-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-bromo-2-(4′-ethyl-biphenyl-4-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4′-ethyl-biphenyl-4-carbonyl)-8-fluoro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [6-chloro-2-(4′-ethyl-biphenyl-4-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [7-chloro-2-(4′-ethyl-biphenyl-4-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-chloro-2-(4′-ethyl-biphenyl-4-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4′-ethyl-biphenyl-4-carbonyl)-8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-methyl-2-(2-naphthalen-1-yl-acetyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [6-chloro-2-(2-naphthalen-1-yl-acetyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-chloro-2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [6-chloro-2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [7-methyl-2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-methyl-2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-bromo-2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-fluoro-2-(naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-fluoro-2-(2-naphthalen-1-yl-acetyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-bromo-3-methyl-benzoyl)-7-chloro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-bromo-3-methyl-benzoyl)-8-chloro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-bromo-3-methyl-benzoyl)-6-chloro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-bromo-3-methyl-benzoyl)-7-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-bromo-3-methyl-benzoyl)-8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-bromo-2-(2-bromo-3-methyl-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-bromo-3-methyl-benzoyl)-8-fluoro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-bromo-2-(2-ethoxy-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-ethoxy-naphthalene-1-carbonyl)-8-fluoro-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [8-chloro-2-(2-ethoxy-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-methoxy-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(5-bromo-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-methyl-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-methyl-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(biphenyl-3-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-fluoro-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-methoxy-naphthalene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   2-(9-oxo-9H-fluorene-2-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(9H-fluorene-1-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(9H-fluorene-4-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2,4,6-trifluoro-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-cyclohexyl-benzoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(1H-indole-4-carbonyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(2-fluoro-phenylcarbamoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(3-fluoro-phenylcarbamoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-fluoro-phenylcarbamoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   (2-o-tolylcarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-m-tolylcarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-p-tolylcarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzylcarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-phenethylcarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   [2-(naphthalen-1-ylcarbamoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(naphthalen-2-ylcarbamoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(biphenyl-2-ylcarbamoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   (2-cyclohexylcarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   [2-(2-chloro-phenylcarbamoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   [2-(4-fluoro-phenylthiocarbamoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   (2-phenylthiocarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-phenethylthiocarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-cyclohexylthiocarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-benzylthiocarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   [2-(2-chloro-phenylthiocarbamoyl)-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-acetic acid;   (2-p-tolylthiocarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   (2-m-tolylthiocarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid; or   (2-o-tolylthiocarbamoyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-acetic acid;   
     or a salt of the compound. 
   
   
       13 . (canceled) 
   
   
       14 . A pharmaceutical composition comprising at least one compound according to any one of  claim 1 ,  10 , or  12  and an inert carrier material and/or adjuvant. 
   
   
       15 . (canceled) 
   
   
       16 . A method of antagonizing prostaglandin D2 mediated hCRTH2 receptor activity comprising administering to a subject in need thereof an effective amount of the compound according to any one of  claim 1 ,  10 , or  12 . 
   
   
       17 . The method of  claim 16 , wherein the subject suffers from at least one of allergic asthma, rhinitis, allergic nephritis, conjunctivitis, atopic dermatitis, bronchial asthma, food allergy, anaphylactic shock, urticaria, eczema, itching, Churg-Strauss syndrome, or sinusitis. 
   
   
       18 . The compound according to any one of  claims 1 - 3 , wherein R2 is methyl, fluoro, chloro, bromo, and trifluoromethyl; R3 is hydrogen or chloro; and R1 and R4 are both hydrogen; or a salt of the compound.