Claims for Patent: 8,039,474

Summary for Patent: 8,039,474

Title:	2,3,4,9-tetrahydro-1H-carbazole derivatives as CRTH2 receptor antagonists
Abstract:	The invention relates to novel tetrahydro-1H-carbazole 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 containing one or more of those compounds and methods of treatment comprising administration of said compounds to patients.
Inventor(s):	Fecher; Anja (Basel, CH), Fretz; Heinz (Riehen, CH), Riederer; Markus (Liestal, CH)
Assignee:	Actelion Pharmaceutical Ltd. (Allschwil, CH)
Application Number:	11/722,095
Patent Claims:	1. A compound of Formula I: ##STR00013## wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 independently represent hydrogen, alkyl, alkoxy, halogen, nitro, cyano, trifluoromethyl, or formyl; R.sup.5 represents hydrogen, alkyl, or --CF.sub.3; and R.sup.6 represents alkoxy, benzyloxy, 1-phenyl-ethoxy, or --NR.sup.7R.sup.8, wherein R.sup.7 and R.sup.8 independently represent hydrogen; alkyl; cyano-alkyl alkenyl; a phenyl or naphthyl group, said groups being optionally mono-substituted by halogen, alkyl, alkoxy, --CF.sub.3, --OCF.sub.3, phenyl-alkyl or phenyl-carbonyl; a phenyl or naphthyl group, said groups being di-substituted with a halogen, alkoxy or phenyl; phenyl-alkyl optionally substituted in the alkyl chain by phenyl or optionally substituted in the phenyl ring by methylendioxy; phenyl-alkyl which is di-substituted by halogen or mono-substituted by halogen, --CF.sub.3, --OCHF.sub.2, alkyl or alkylsulfanyl; naphthyl-alkyl; phenylcarbonyl; cycloalkyl, wherein cycloalkyl refers to a cyclopentyl or cyclohexyl group, wherein said groups are optionally substituted with an annulated benzene ring; pyridyl-alkyl; thienyl-alkyl; furanyl-alkyl; or imidazolyl-alkyl; or R.sup.7 and R.sup.8, together with the nitrogen atom to which they are attached, form a heterocyclic 5-, 6-, 7-, or 8-membered ring system with 1 or 2 nitrogen and which ring system is optionally substituted with (i) one or two annulated benzene rings, wherein the benzene rings are unsubstituted or substituted with one or two C1-C4 alkyl, C1-C4 alkoxy, halogen, --CF.sub.3, or --OCF.sub.3; (ii) an unsubstituted phenyl ring; (iii) a mono- or di-substituted phenyl ring, wherein the substituents are halogen, C1-C4 alkyl, C1-C4 alkoxy, --CF.sub.3, and --OCF.sub.3; or (iv) phenyl-alkyl wherein the alkyl chain is substituted by phenyl; or an optically pure enantiomer, a mixture of enantiomers, an optically pure diastereomer, a mixture of diastereomers, a mixture of an enantiomer and a diasteromer, a meso form, or a geometric isomer, thereof; or a pharmaceutically acceptable salt thereof. 2. The compound according to claim 1, wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 independently represent hydrogen, alkyl, alkoxy, halogen, nitro, cyano, trifluoromethyl, or formyl; R.sup.5 represents hydrogen, alkyl, or --CF.sub.3; and R.sup.6 represents alkoxy; benzyloxy; 1-phenyl-ethoxy; or --NR.sup.7R.sup.8, wherein R.sup.7 and R.sup.8 independently represent hydrogen; alkyl; cyano-alkyl; alkenyl; phenyl optionally mono-substituted by halogen, alkyl, alkoxy, --CF.sub.3, --OCF.sub.3, phenyl-alkyl or phenyl-carbonyl; phenyl, di-substituted with halogen, alkoxy and phenyl; naphthyl; phenyl-alkyl optionally substituted in the alkyl chain by phenyl or optionally substituted in the phenyl ring by methylendioxy; phenyl-alkyl which is di-substituted by halogen or mono-substituted by halogen, --CF.sub.3, --OCHF.sub.2, alkyl or alkylsulfanyl; naphthyl-alkyl; phenylcarbonyl; cycloalkyl, wherein cycloalkyl refers to a cyclopentyl or cyclohexyl group, wherein said groups are optionally substituted with an annulated benzene ring; pyridyl-alkyl; thienyl-alkyl; furanyl-alkyl; or imidazolyl-alkyl; or R.sup.7 and R.sup.8, together with the nitrogen atom to which they are attached, form a heterocyclic 5-, 6-, 7-, or 8-membered ring system with 1 or 2 nitrogen heteroatoms and which ring system is optionally substituted with (i) one or two annulated benzene rings, wherein the benzene rings are unsubstituted or substituted with one or two C1-C4 alkyl, C1-C4 alkoxy, halogen, --CF.sub.3, or --OCF.sub.3; (ii) an unsubstituted phenyl ring; or (iii) a mono- or di-substituted phenyl ring substituted with halogen, C1-C4 alkyl, C1-C4 alkoxy, --CF.sub.3, or --OCF.sub.3; or a pharmaceutically acceptable salt thereof. 3. The compound according to claim 1 or 2, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represent C.sub.1-C.sub.4 alkyl, C.sub.1-C.sub.4 alkoxy, halogen, nitro, cyano, or trifluoromethyl; or a pharmaceutically acceptable salt thereof. 4. The compound according to claim 1 or 2, wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 independently represent methyl, trifluoromethyl, methoxy, fluoro, chloro, bromo, or iodo; or a pharmaceutically acceptable salt thereof. 5. The compound according to claim 1 or 2, wherein R.sup.7 represents alkenyl; alkyl; phenyl-C1-C4 alkyl optionally substituted in the alkyl chain by phenyl or optionally substituted in the phenyl ring by methylendioxy; phenyl-C1-C4 alkyl which is di-substituted by halogen or mono-substituted by halogen, --CF.sub.3, --OCHF.sub.2, alkyl or alkylsulfanyl; naphthyl-C1-C4 alkyl; cycloalkyl, wherein cycloalkyl refers to a cyclopentyl or cyclohexyl group, wherein said groups are optionally substituted with an annulated benzene ring; thienyl-C1-C4 alkyl; furanyl-C1-C4 alkyl; pyridyl-C1-C4 alkyl; or imidazolyl-C1-C4 alkyl; and R.sup.8 represents hydrogen; phenyl optionally mono-substituted by halogen, alkyl, alkoxy, --CF.sub.3, --OCF.sub.3, phenyl-alkyl or phenyl-carbonyl; phenyl, di-substituted with halogen, alkoxy or phenyl; naphthyl; phenyl-C1-C4 alkyl optionally substituted in the alkyl chain by phenyl or optionally substituted in the phenyl ring by methylendioxy; phenyl-C1-C4 alkyl which is di-substituted by halogen or mono-substituted by halogen, --CF.sub.3, --OCHF.sub.2, alkyl or alkylsulfanyl; naphthyl-C1-C4 alkyl; furanyl-C1-C4 alkyl, pyridyl-C1-C4 alkyl, or thienyl-C1-C4 alkyl; or a pharmaceutically acceptable salt thereof. 6. The compound according to, wherein R.sup.7 represents hydrogen, allyl, 2-cyano-ethyl, methyl, butyl, ethyl, isopropyl, benzyl, 1-phenyl-ethyl, 2-phenyl-ethyl, phenyl-propyl, cyclohexyl, or thiophen-3-ylmethyl; and R.sup.8 represents phenyl, 2-benzyl-phenyl, 2-methoxy-phenyl, 2-methyl-phenyl, 2-trifluoromethyl-phenyl, 3,4-dichloro-phenyl, 3-benzoyl-phenyl, 3-chloro-phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-chloro-phenyl, 4-fluoro-phenyl, 4-methoxy-biphenyl-3-yl, 4-trifluoromethoxy-phenyl, 5-chloro-2-methoxy-phenyl, naphthalen-1-yl, benzo[1,3]dioxol-5-ylmethyl, benzyl, diphenylmethyl, 1-phenyl-ethyl, 2-phenyl-ethyl, 2-pyridin-2-yl-ethyl, 3,4-dichloro-benzyl, 2,4-dichloro-benzyl, difluoromethoxy-benzyl, 2-chloro-benzyl, 4-chloro-benzyl, 2-methylsulfanyl-benzyl, 2-fluoro-benzyl, 3-fluoro-benzyl, 4-fluoro-benzyl, 2-trifluoromethyl-benzyl, 3-trifluoromethyl-benzyl, 2,4-difluoro-benzyl, 2,5-difluoro-benzyl, 2,6-difluoro-benzyl, 3,5-difluoro-benzyl, 4-chloro-2-fluoro-benzyl, (2-fluoro-phenyl)-ethyl, (3-fluoro-phenyl)-ethyl, (4-fluoro-phenyl)-ethyl, (4-chloro-phenyl)-ethyl, (2,6-dichloro-phenyl)-ethyl, naphthalene-1-ylmethyl, 1,2,3,4-tetrahydro-naphthalen-1-yl, indan-2-yl, or 2,2-diphenyl-ethyl; or a pharmaceutically acceptable salt thereof. 7. The compound according to claim 1 or 2, wherein R.sup.7 and R.sup.8, together with the nitrogen atom to which they are attached, form a dihydro-dibenzo[b,f]azocine, dihydro-indole, dihydroisoquinoline, dihydroquinoline, or dibenzoazepine ring; or a pharmaceutically acceptable salt thereof. 8. The compound according to claim 1 or 2, wherein R.sup.7 and R.sup.8, together with the nitrogen atom to which they are attached, form a heterocyclic ring system which is 11,12-dihydro-6H-dibenzo[b,f]azocine-5-yl, 2,3-dihydro-indole-1-yl, 3,4-dihydro-1H-isoquinoline-2-yl, 3,4-dihydro-2H-quinoline-1-yl, 4-(4-fluoro-phenyl)-piperazine-1-yl, 6,11-dihydro-dibenzo[b,e]azepine-5-yl, 6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-yl, 7-trifluoromethyl-3,4-dihydro-2H-quinoline-1-yl, dibenzo[b,f]azepine-5-yl, 1H,3H-benzo[d,e]isoquinoline-2-yl, 4-benzhydryl-piperazine-1-yl, or azocane-1-yl; or a pharmaceutically acceptable salt thereof. 9. The compound according to claim 1 or 2, wherein R.sup.6 represents (R)-1-phenyl-ethyloxy or benzyloxy; or a pharmaceutically acceptable salt thereof. 10. The compound according to claim 1, wherein R.sup.1, R.sup.2, R.sup.3, and R.sup.4 independently represent hydrogen, alkyl, alkoxy, halogen, nitro, cyano, or trifluoromethyl; R.sup.5 represents hydrogen or alkyl; and R.sup.6 represents benzyloxy, 1-phenyl-ethoxy or --NR.sup.7R.sup.8, wherein R.sup.7 and R.sup.8 independently represent hydrogen; alkyl; cyano-alkyl; alkenyl; phenyl optionally mono-substituted by halogen, alkyl, alkoxy, --CF.sub.3, --OCF.sub.3, phenyl-alkyl or phenyl-carbonyl; phenyl, di-substituted with halogen, alkoxy and phenyl; phenyl-alkyl optionally substituted in the alkyl chain by phenyl or optionally substituted in the phenyl ring by methylendioxy; phenyl-alkyl which is di-substituted by halogen or mono-substituted by halogen, --CF.sub.3, --OCHF.sub.2, alkyl or alkylsulfanyl; naphthyl; naphthyl-alkyl; cycloalkyl, wherein cycloalkyl refers to a cyclopentyl or cyclohexyl group, wherein said groups are optionally substituted with an annulated benzene ring; pyridyl-alkyl; or thienyl-alkyl; or R.sup.7 and R.sup.8, together with the nitrogen atom to which they are attached, form a heterocyclic 5-, 6-, 7-, or 8-membered ring system with one or two nitrogen heteroatoms and which ring system is optionally substituted with (i) one or two annulated benzene rings, wherein the benzene rings are unsubstituted or substituted with one or two substituents of alkoxy or --CF.sub.3; (ii) a mono-substituted phenyl ring substituted with halogen; or (iii) phenyl-alkyl, wherein the alkyl chain is substituted with phenyl; or a pharmaceutically acceptable salt thereof. 11. The compound according to claim 1, wherein the compound is: [3-methyl-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; {3-[(3-chloro-phenyl)-methyl-carbamoyl]-3-methyl-1,2,3,4-tetrahydro-carba- zol-9-yl}-acetic acid; [3-(2,3-dihydro-indole-1-carbonyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acet- ic acid; [3-methyl-3-(phenyl-thiophen-3-ylmethyl-carbamoyl)-1,2,3,4-tetrah- ydro-carbazol-9-yl]-acetic acid; [3-(benzyl-phenyl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; {3-[(4-fluoro-phenyl)-methyl-carbamoyl]-3-methyl-1,2,3,4-tetrahydro-carba- zol-9-yl}-acetic acid; [3-(6,11-dihydro-dibenzo[b,e]azepine-5-carbonyl)-1,2,3,4-tetrahydro-carba- zol-9-yl]-acetic acid; [3-(benzyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; {3-[phenyl-(3-phenyl-propyl)-carbamoyl]-1,2,3,4-tetrahydro-carbazol- -9-yl}-acetic acid; [3-(2,3-dihydro-indole-1-carbonyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9- -yl]-acetic acid; {3-[(3,4-dichloro-phenyl)-methyl-carbamoyl]-3-methyl-1,2,3,4-tetrahydro-c- arbazol-9-yl}-acetic acid; [3-(allyl-phenyl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl]-ac- etic acid; {3-[benzyl-((S)-1-phenyl-ethyl)-carbamoyl]-1,2,3,4-tetrahydro-c- arbazol-9-yl}-acetic acid; {3-[methyl-(2-trifluoromethyl-phenyl)-carbamoyl]-1,2,3,4-tetrahydro-carba- zol-9-yl}-acetic acid; [3-(methyl-phenyl-carbamoyl)-6-trifluoromethyl-1,2,3,4-tetrahydro-carbazo- l-9-yl]-acetic acid; [3-methyl-3-(methyl-o-tolyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-- acetic acid; [3-(2-benzyl-phenylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; [3-(dibenzo[b,f]azepine-5-carbonyl)-1,2,3,4-tetrahydro-carbazol-9-y- l]-acetic acid; [3-(ethyl-naphthalen-1-yl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-ac- etic acid; [3-(benzhydryl-methyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-- yl]-acetic acid; {3-methyl-3-[phenyl-(3-phenyl-propyl)-carbamoyl]-1,2,3,4-tetrahydro-carba- zol-9-yl}-acetic acid; [3-(ethyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; [3-(phenyl-thiophen-3-ylmethyl-carbamoyl)-1,2,3,4-tetrahydro-carbaz- ol-9-yl]-acetic acid; [3-(benzyl-isopropyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; {3-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-1,2,3,4-tetrahydro-c- arbazol-9-yl}-acetic acid; [3-(benzyl-phenethyl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl- ]-acetic acid; [3-(3,4-dihydro-2H-quinoline-1-carbonyl)-1,2,3,4-tetrahydro-carbazol-9-yl- ]-acetic acid; [3-(cyclohexyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; {3-[(3-chloro-phenyl)-methyl-carbamoyl]-1,2,3,4-tetrahydro-carbazol- -9-yl}-acetic acid; [3-methyl-3-(phenethyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl- ]-acetic acid; [3-(2-methoxy-phenylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; [3-(allyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-aceti- c acid; [3-(benzyl-phenethyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-- acetic acid; [3-(phenethyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; [3-(methyl-o-tolyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-ace- tic acid; {3-[benzyl-((R)-1-phenyl-ethyl)-carbamoyl]-1,2,3,4-tetrahydro-ca- rbazol-9-yl}-acetic acid; [3-(methyl-phenyl-carbamoyl)-6-nitro-1,2,3,4-tetrahydro-carbazol-9-yl]-ac- etic acid; [3-(7-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carbonyl)-1,2,- 3,4-tetrahydro-carbazol-9-yl]-acetic acid; [3-(3,4-dihydro-2H-quinoline-1-carbonyl)-3-methyl-1,2,3,4-tetrahydro-carb- azol-9-yl]-acetic acid; {3-[(4-fluoro-phenyl)-methyl-carbamoyl]-1,2,3,4-tetrahydro-carbazol-9-yl}- -acetic acid; [3-(4-methoxy-biphenyl-3-ylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; [6-fluoro-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; [7-chloro-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; [6-chloro-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; {3-[methyl-(2-pyridin-2-yl-ethyl)-carbamoyl]-1,2,3,4-tetrahydro-carbazol-- 9-yl}-acetic acid; {3-[(4-chloro-phenyl)-methyl-carbamoyl]-1,2,3,4-tetrahydro-carbazol-9-yl}- -acetic acid; {(R)-3-[(4-chloro-phenyl)-methyl-carbamoyl]-1,2,3,4-tetrahydro-carbazol-9- -yl}-acetic acid; [3-(isopropyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; {3-[(3,4-dichloro-phenyl)-methyl-carbamoyl]-1,2,3,4-tetrahydro-carb- azol-9-yl}-acetic acid; [3-(benzhydryl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; [6-cyano-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-ac- etic acid; {3-[benzyl-((R)-1-phenyl-ethyl)-carbamoyl]-3-methyl-1,2,3,4-tet- rahydro-carbazol-9-yl}-acetic acid; [3-(2-benzyl-phenylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl]-- acetic acid; [6-isopropyl-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl- ]-acetic acid; [6-methyl-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; [3-(11,12-dihydro-6H-dibenzo[b,f]azocine-5-carbonyl)-1,2,3,4-tetrahydro-c- arbazol-9-yl]-acetic acid; [3-(methyl-phenethyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; [6-bromo-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-- yl]-acetic acid; [3-(3-benzoyl-phenylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; (3-dibenzylcarbamoyl-1,2,3,4-tetrahydro-carbazol-9-yl)-acetic acid; [3-(ethyl-naphthalen-1-yl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol- -9-yl]-acetic acid; {3-[(3-fluoro-phenyl)-methyl-carbamoyl]-1,2,3,4-tetrahydro-carbazol-9-yl}- -acetic acid; {3-[benzyl-(2-cyano-ethyl)-carbamoyl]-1,2,3,4-tetrahydro-carbazol-9-yl}-a- cetic acid; (3-phenylcarbamoyl-1,2,3,4-tetrahydro-carbazol-9-yl)-acetic acid; [3-(isopropyl-phenyl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazo- l-9-yl]-acetic acid; (3-diphenethylcarbamoyl-1,2,3,4-tetrahydro-carbazol-9-yl)-acetic acid; [3-(benzhydryl-methyl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-y- l]-acetic acid; [3-(5-chloro-2-methoxy-phenylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]- -acetic acid; [3-(butyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; {3-[ethyl-(4-trifluoromethoxy-phenyl)-carbamoyl]-1,2,3,4-tetrahydro- -carbazol-9-yl}-acetic acid; [3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; [6-iodo-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-y- l]-acetic acid; [6-methoxy-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-- acetic acid; 9-carboxymethyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid (R)-1-phenyl-ethyl ester; (S)-3-[(4-chloro-phenyl)-methyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-- yl]-acetic acid; [3-(6,11-dihydro-dibenzo[b,e]azepine-5-carbonyl)-3-methyl-1,2,3,4-tetrahy- dro-carbazol-9-yl]-acetic acid; [8-chloro-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; 9-carboxymethyl-2,3,4,9-tetrahydro-1H-carbazole-3-carboxylic acid benzyl ester; [3-(3,4-dihydro-1H-isoquinoline-2-carbonyl)-1,2,3,4-tetrahydro-carbazol-9- -yl]-acetic acid; [3-(6,7-dimethoxy-3,4-dihydro-1H-isoquinoline-2-carbonyl)-1,2,3,4-tetrahy- dro-carbazol-9-yl]-acetic acid; {3-[(benzo[1,3[dioxol-5-ylmethyl)-carbamoyl]-1,2,3,4-tetrahydro-carbazol-- 9-yl}-acetic acid; and or [3-(cyclohexyl-phenyl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-y- l]-acetic acid; or a pharmaceutically acceptable salt thereof. 12. The compound according to claim 1, wherein the compound is: {3-[benzyl-((R)-1-phenyl-ethyl)-carbamoyl]-6-fluoro-1,2,3,4-tetrahydro-ca- rbazol-9-yl}-acetic acid; [3-(benzhydryl-methyl-carbamoyl)-6-fluoro-1,2,3,4-tetrahydro-carbazol-9-y- l]-acetic acid; {3-[benzyl-((S)-1-phenyl-ethyl)-carbamoyl]-6-fluoro-1,2,3,4-tetrahydro-ca- rbazol-9-yl}-acetic acid; [3-(benzyl-phenethyl-carbamoyl)-6-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl- ]-acetic acid; [3-(2,3-dihydro-indole-1-carbonyl)-6-fluoro-1,2,3,4-tetrahydro-carbazol-9- -yl]-acetic acid; [3-(benzyl-isopropyl-carbamoyl)-6-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl- ]-acetic acid; [3-(azocane-1-carbonyl)-6-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; (3-phenylcarbamoyl-3-propyl-1,2,3,4-tetrahydro-carbazol-9-yl)-aceti- c acid; [3-(methyl-phenyl-carbamoyl)-3-propyl-1,2,3,4-tetrahydro-carbazol-- 9-yl]-acetic acid; [6-fluoro-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; {6-fluoro-3-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-1,2,3,4-tetrahydr- o-carbazol-9-yl}-acetic acid; [3-(4-fluoro-phenylcarbamoyl)-3-propyl-1,2,3,4-tetrahydro-carbazol-9-yl]-- acetic acid; {6-fluoro-3-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-1,2,3,4-tetrahydr- o-carbazol-9-yl}-acetic acid; [3-(benzhydryl-methyl-carbamoyl)-6-fluoro-1,2,3,4-tetrahydro-carbazol-9-y- l]-acetic acid; (3-{benzyl-[2-(2,6-dichloro-phenyl)-ethyl]-carbamoyl}-1,2,3,4-tetrahydro-- carbazol-9-yl)-acetic acid; {3-[benzyl-((S)-1-phenyl-ethyl)-carbamoyl]-6-fluoro-1,2,3,4-tetrahydro-ca- rbazol-9-yl}-acetic acid; [3-(3-fluoro-phenylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl]-- acetic acid; [3-(3,5-difluoro-benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-- yl]-acetic acid; [3-(3-fluoro-phenylcarbamoyl)-3-propyl-1,2,3,4-tetrahydro-carbazol-9-yl]-- acetic acid; [3-(3-fluoro-phenylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; [3-(2,3-dihydro-indole-1-carbonyl)-3-ethyl-1,2,3,4-tetrahydro-carba- zol-9-yl]-acetic acid; [3-ethyl-3-(3-fluoro-phenylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; [3-ethyl-3-(4-fluoro-phenylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; [3-(2-chloro-benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl]-- acetic acid; [3-(benzyl-phenethyl-carbamoyl)-6-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl- ]-acetic acid; [3-methyl-3-(2-methylsulfanyl-benzylcarbamoyl)-1,2,3,4-tetrahydro-carbazo- l-9-yl]-acetic acid; (3-ethyl-3-phenylcarbamoyl-1,2,3,4-tetrahydro-carbazol-9-yl)-acetic acid; {3-[benzyl-((R)-1-phenyl-ethyl)-carbamoyl]-6-fluoro-1,2,3,4-tetrahydro-ca- rbazol-9-yl}-acetic acid; [3-ethyl-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-ac- etic acid; [3-(2-fluoro-phenylcarbamoyl)-3-propyl-1,2,3,4-tetrahydro-carba- zol-9-yl]-acetic acid; [3-(2-fluoro-phenylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl]-- acetic acid; {3-methyl-3-[(naphthalen-1-ylmethyl)-carbamoyl]-1,2,3,4-tetrahydro-carbaz- ol-9-yl}-acetic acid; {3-[benzyl-(2-cyano-ethyl)-carbamoyl]-3-methyl-1,2,3,4-tetrahydro-carbazo- l-9-yl}-acetic acid; [3-(benzyl-butyl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl]-ac- etic acid; [3-(4-fluoro-phenylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carba- zol-9-yl]-acetic acid; [3-(4-fluoro-phenylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; [3-(2,4-dichloro-benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carba- zol-9-yl]-acetic acid; (3-[benzyl-(4-fluoro-benzyl)-carbamoyl)-(4-tetrahydro-carbazol-9-yl]-acet- ic acid; [3-(benzyl-isopropyl-carbamoyl)-6-fluoro-1,2,3,4-tetrahydro-carba- zol-9-yl]-acetic acid; [3-(2-difluoromethoxy-benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbaz- ol-9-yl]-acetic acid; [3-(2-fluoro-phenylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; [3-(benzyl-ethyl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-- yl]-acetic acid; (3-methyl-3-phenylcarbamoyl-1,2,3,4-tetrahydro-carbazol-9-yl)-acetic acid; [3-ethyl-3-(2-fluoro-phenylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9- -yl]-acetic acid; [3-(4-chloro-benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl]-- acetic acid; (3-{benzyl-[2-(4-fluoro-phenyl)-ethyl]-carbamoyl}-1,2,3,4-tetrahydro-carb- azol-9-yl)-acetic acid; [3-methyl-3-(4-pentyl-benzylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-- acetic acid; {3-[benzyl-(4-chloro-2-fluoro-benzyl)-carbamoyl]-1,2,3,4-tetrahydro-carba- zol-9-yl}-acetic acid; [3-(azocane-1-carbonyl)-6-fluoro-1,2,3,4-tetrahydro-carbazol-9-yl]-acetic acid; [3-(2-fluoro-benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-- 9-yl]-acetic acid; [3-(3,4-dichloro-benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-- yl]-acetic acid; (3-{benzyl-[2-(4-chloro-phenyl)-ethyl]-carbamoyl}-1,2,3,4-tetrahydro-carb- azol-9-yl)-acetic acid; [3-(2,4-difluoro-benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-- yl]-acetic acid; [3-(benzhydryl-carbamoyl)-3-propyl-1,2,3,4-tetrahydro-carbazol-9-yl]-acet- ic acid; {8-chloro-3-[4-(4-fluoro-phenyl)-piperazine-1-carbonyl]-1,2,3,4-t- etrahydro-carbazol-9-yl}-acetic acid; [8-chloro-3-(2,3-dihydro-indole-1-carbonyl)-1,2,3,4-tetrahydro-carbazol-9- -yl]-acetic acid; [3-(2,6-difluoro-benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-- yl]-acetic acid; {3-[benzyl-(3-fluoro-benzyl)-carbamoyl]-1,2,3,4-tetrahydro-carbazol-9-yl}- -acetic acid; [3-(benzhydryl-methyl-carbamoyl)-8-chloro-1,2,3,4-tetrahydro-carbazol-9-y- l]-acetic acid; [3-(benzhydryl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl]-acet- ic acid; {3-[benzyl-(3-trifluoromethyl-benzyl)-carbamoyl]-1,2,3,4-tetrahyd- ro-carbazol-9-yl}-acetic acid; [3-(benzhydryl-carbamoyl)-3-ethyl-1,2,3,4-tetrahydro-carbazol-9-yl]-aceti- c acid; [3-(4-fluoro-benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol- -9-yl]-acetic acid; (3-{benzyl-[2-(3-fluoro-phenyl)-ethyl]-carbamoyl}-1,2,3,4-tetrahydro-carb- azol-9-yl)-acetic acid; [3-(benzyl-isopropyl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl- ]-acetic acid; {3-[benzyl-(3,5-difluoro-benzyl)-carbamoyl]-1,2,3,4-tetrahydro-carbazol-9- -yl}-acetic acid; (3-{benzyl-[2-(2-fluoro-phenyl)-ethyl]-carbamoyl}-1,2,3,4-tetrahydro-carb- azol-9-yl)-acetic acid; {3-[benzyl-(2-trifluoromethyl-benzyl)-carbamoyl]-1,2,3,4-tetrahydro-carba- zol-9-yl}-acetic acid; {3-[benzyl-(4-fluoro-benzyl)-carbamoyl]-3-methyl-1,2,3,4-tetrahydro-carba- zol-9-yl}-acetic acid; [3-(1H,3H-benzo[de]isoquinoline-2-carbonyl)-3-methyl-1,2,3,4-tetrahydro-c- arbazol-9-yl]-acetic acid; {3-[benzyl-(2,5-difluoro-benzyl)-carbamoyl]-1,2,3,4-tetrahydro-carbazol-9- -yl}-acetic acid; {3-[benzyl-(3-fluoro-benzyl-carbamoyl]-3-methyl-1,2,3,4-tetrahydro-carbaz- ol-9-yl}-acetic acid; {3-methyl-3-[(R)-(1,2,3,4-tetrahydro-naphthalen-1-yl)carbamoyl]-1,2,3,4-t- etrahydro-carbazol-9-yl}-acetic acid; {3-[benzyl-(3,5-difluoro-benzyl)-carbamoyl]-3-methyl-1,2,3,4-tetrahydro-c- arbazol-9-yl}-acetic acid; [3-(benzyl-methyl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; (3-{benzyl-[2-(4-chloro-phenyl)-ethyl]-carbamoyl}-3-methyl-1,2,3,4-tetrah- ydro-carbazol-9-yl)-acetic acid; (3-{benzyl-[2-(4-fluoro-phenyl)-ethyl]-carbamoyl}-3-methyl-1,2,3,4-tetrah- ydro-carbazol-9-yl)-acetic acid; [8-chloro-3-(2,2-diphenyl-ethylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-y- l]-acetic acid; {3-[benzyl-(3-trifluoromethyl-benzyl)-carbamoyl]-3-methyl-1,2,3,4-tetrahy- dro-carbazol-9-yl}-acetic acid; [3-(4-benzhydryl-piperazine-1-carbonyl)-8-chloro-1,2,3,4-tetrahydro-carba- zol-9-yl]-acetic acid; {3-[benzyl-(4-chloro-2-fluoro-benzyl)-carbamoyl]-3-methyl-1,2,3,4-tetrahy- dro-carbazol-9-yl}-acetic acid; [3-(benzhydryl-carbamoyl)-8-chloro-1,2,3,4-tetrahydro-carbazol-9-yl]-acet- ic acid; [3-(2,3-dihydro-indole-1-carbonyl)-3-propyl-1,2,3,4-tetrahydro-ca- rbazol-9-yl]-acetic acid; (3-{benzyl-[2-(3-fluoro-phenyl)-ethyl]-carbamoyl}-3-methyl-1,2,3,4-tetrah- ydro-carbazol-9-yl)-acetic acid; (3-{benzyl-[2-(2,6-dichloro-phenyl)-ethyl]-carbamoyl}-3-methyl-1,2,3,4-te- trahydro-carbazol-9-yl)-acetic acid; {3-[benzyl-(2-trifluoromethyl-benzyl)-carbamoyl]-3-methyl-1,2,3,4-tetrahy- dro-carbazol-9-yl}-acetic acid; {3-[benzyl-(2,5-difluoro-benzyl)-carbamoyl]-3-methyl-1,2,3,4-tetrahydro-c- arbazol-9-yl}-acetic acid; [8-chloro-3-(indan-2-yl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-acet- ic acid; (3-{benzyl-[2-(2-fluoro-phenyl)-ethyl]-carbamoyl}-3-methyl-1,2,3,- 4-tetrahydro-carbazol-9-yl)-acetic acid; [6-fluoro-3-((R)-1-phenyl-ethylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-y- l]-acetic acid; [6-fluoro-3-((R)-1-phenyl-ethylcarbamoyl)-1,2,3,4-tetrahydro-carbazol-9-y- l]-acetic acid; [3-(benzyl-cyanomethyl-carbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-- yl]-acetic acid; [3-(2,3-dichloro-benzylcarbamoyl)-3-methyl-1,2,3,4-tetrahydro-carbazol-9-- yl]-acetic acid; or [7-methyl-3-(methyl-phenyl-carbamoyl)-1,2,3,4-tetrahydro-carbazol-9-yl]-a- cetic acid; or a pharmaceutically acceptable salt thereof. 13. A pharmaceutical composition comprising the compound according to claim 1 or 2 and a pharmaceutically acceptable carrier. 14. A method of antagonizing a CRTH2 receptor, comprising administering to a subject in need thereof an antagonistic amount of the compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein the antagonistic amount treats allergic asthma, rhinitis, allergic nephritis, conjunctivitis, atopic dermatitis, bronchial asthma, food allergy, anaphylactic shock, urticaria, eczema, itching, Churg-Strauss syndrome, or sinusitis.