DE10130830A1 - Indole derivatives - Google Patents

Abstract

The invention relates to new indole derivatives, processes for their preparation and their use in medicaments.

Description

The invention relates to new indole derivatives, processes for their preparation and their Use in medicines.

EP-A-580 550 describes oxamic acid derivatives which cholesterol-isolate have characteristic properties in mammals. As a pharmacological property is the reduction of plasma cholesterol, especially of LDL cholesterol pre-stressed. Cholesterol-lowering effects are also described in EP-A-188 351 wrote for certain diphenyl ethers with thyroid hormone-like effects, which clearly differ in their chemical structure from the compound according to the invention differentiate.

WO 00/51971 discloses oxamic acid derivatives with an indole partial structure as thyroid Receptor ligands for the treatment of various diseases.

Further indoles which are in the 5-position via a bridge member with a substituted one Phenyl ring are known (WO 94/14770; EP-A-674 619 A1 or WO 94/26737). These 5-substituted indoles are not thyroid hormone-like Properties described.

WO 99/50268 discloses substituted indolalkane carboxylic acids which are suitable for the Be chronic complications caused by diabetes mellitus.

WO 95/20588 discloses indole derivatives which act as 5-HT ₁ agonists.

WO 98/11895 discloses the use of 5-HT ₁ agonists for the treatment of migraines; Indole derivatives are also indicated as suitable active ingredients. WO 98/06402 describes the use of the same structures for the treatment of cold or rhinitis.

EP-A-639 573 discloses benzo-fused 5-ring heterocycles and their use in medicines and diagnostics. The compounds disclosed are inhibitors of the cellular sodium proton antiporter (Na ⁺ / H ⁺ exchanger).

US-A-5 468 899 relates to bicyclic aryl compounds with selective properties as LTB ₄ antagonists.

EP-A-377 450 discloses substituted indole, benzofuran and benzothiophene deri vate with effect as 5-lipoxygenase inhibitors.

JP-A-07145 147 discloses testosterone-5-alpha derived from benzoic acid Reductase inhibitors used to treat prostate cancer and certain hair default diseases can be used.

GB-A-2 253 848 describes di-ortho-substituted phenyl-indole in the phenyl part Described ethers with herbicidal activity, which are used as crop protection agents can be. Thyromimetic effects are ortho-substituted for these Indole has not yet become known.

The object of the invention is to provide new compounds with improved, especially pharmaceutical effects.

It has now been found that compounds of the general formula (I)

in which
Z represents O, S, SO, SO ₂ , CH ₂ , CHF, CF ₂ or NR ⁹ , where R ^{9 is} hydrogen or (C ₁ -C ₄ ) alkyl,
R ¹ and R ^{2 are} identical or different and represent hydrogen, halogen, cyano, (C ₁ - C ₆ ) alkyl, CF ₃ , CHF ₂ , CH ₂ F, vinyl or (C ₃ -C ₇ ) cycloalkyl, where at least one of the two substituents is not hydrogen and is in the ortho position to the bridge bond,
R ³ for a group of the formula

-A _m -D _n -E _o -G _p -LR ¹⁰

stands in what
A represents O, S, NR ¹¹ or the group - (CR ¹² = CR ¹³ ) -, in which R ^{11 is} hydrogen or (C ₁ -C ₄ ) alkyl, and R ¹² and R ^{13 are} identical or different and Is hydrogen, cyano, (C ₁ -C ₄ ) -alkyl or (C ₁ -C ₄ ) -alkoxy,
D represents a straight-chain (C ₁ -C ₃ ) alkylene group which, one or more times, the same or different, by (C ₁ -C ₄ ) alkyl, hydroxy, (C ₁ -C ₄ ) alkoxy, halogen, Amino, mono- (C ₁ -C ₄ ) -alkylamino, mono- (C ₁ -C ₄ ) -acylamino or (C ₁ -C ₄ ) -alkoxycarbonylamino may be substituted,
E and L independently of one another represent a C (O) or SO ₂ group,
G represents NR ¹⁴ , in which R ^{14 represents} hydrogen or (C ₁ -C ₄ ) -alkyl, or represents a straight-chain (C ₁ -C ₃ ) -alkylene group which is one or more times, identical or different, by (C ₁ -C ₄ ) alkyl, hydroxy, (C ₁ -C ₄ ) alkoxy, halogen, amino, mono- or di- (C ₁ -C ₄ ) alkylamino or mono- (C ₁ -C ₄ ) acylamino can be substituted
m, n, o and p each independently represent the number 0 or 1, with the proviso that
in the event that L stands for a C = O group, the sum (m + n + o + p) is not equal to the number 0,
and
in the event that m and o each represent the number 1, A the remainder NR ¹¹ and E and L each represent a C = O group, the sum (n + p) is not equal to the number 0,
and
R ¹⁰ for OR ¹⁵ , NR ¹⁶ R ¹⁷ , (C ₁ -C ₁₀ ) alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₂ -C ₆ ) alkenyl, (C ₆ -C ₁₀ ) aryl , (C ₆ -C ₁₀ ) arylmethyl or a saturated, partially unsaturated or aromatic 5- to 10-membered heterocycle with up to four identical or different hetero atoms from the series N, O and / or S, where the aforementioned radicals optionally by one, two or three identical or different substituents selected from the group halogen, hydroxy, oxo, cyano, nitro, amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ -C ₆ ) alkyl, optionally by R. ²⁰ substituted (C ₁ -C ₆ ) alkoxy, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, which in turn may be substituted by halogen, (C ₁ -C ₄ ) alkyl, (C ₁ -C ₄ ) alkoxy, trifluoromethyl, nitro or cyano, -OC (O) -R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ -NR ²⁵ R ²⁶ , -NH-C (O) -R ²⁷ and -NH-C (O) -OR ^{28 are} substituted, wherein
R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each represents hydrogen, Phenyl, benzyl, (C ₁ -C ₆ ) alkyl or (C ₃ -C ₈ ) cycloalkyl, which in turn are optionally one or more, identical or different, by halogen, hydroxyl, amino, carboxyl, (C ₁ - C ₄ ) alkoxy, (C ₁ -C ₄ ) alkoxycarbonyl, (C ₁ -C ₄ ) alkoxy carbonylamino, (C ₁ -C ₅ ) alkanoyloxy, a heterocycle or phenyl which is optionally substituted by halogen or hydroxy,
or the group
-LR ¹⁰ for a group of the formula

stands in what
R ²⁹ denotes hydrogen or (C ₁ -C ₄ ) alkyl,
or
R ³ for a group of the formula

stands in what
Q represents a 5- to 6-membered saturated, partially unsaturated or aromatic heterocycle having up to four identical or different heteroatoms from the series N, O and / or S, which in turn may be mono- to triple, identical or different Oxo (= O), thioxo (= S), hydroxy, (C ₁ -C ₆ ) alkyl or phenyl is substituted,
r represents the number 0, 1 or 2,
and
the ring Het is a 5- to 6-membered saturated or partially unsaturated heterocycle with up to three identical or different hetero atoms from the series N, O and / or S, which is optionally one to three times, identical or different, by oxo ( = O), thioxo (= S), hydroxy, (C ₁ -C ₆ ) alkyl or phenyl,
R ⁴ and R ^{5 are the} same or different and each represents hydrogen, hydroxy, halogen, cyano, nitro, (C ₁ -C ₄ ) alkyl or the rest of the formula NR ³⁰ R ³¹ , where R ³⁰ and R ^{31 are} the have the meaning given for R ¹⁵ and, independently of one another, may be the same or different with this substituent,
R ^{6 represents} hydrogen, halogen or a group of the formula

-M _a -R ³²

stands in what
M represents a carbonyl group, a sulfonyl group or a methylene group,
a represents the number 0 or 1,
and
R ^{32 has} the meaning of R ¹⁰ given above and can be identical or different with this substituent,
R ^{7 represents} hydrogen or an acyl group which can be split off under physiological conditions to form an NH function, preferably represents hydrogen or acetyl,
and
R ^{8 has} the meaning of R ⁶ given above and can be identical or different with this substituent,
as well as their pharmaceutically acceptable salts, solvates, hydrates and hydrates of the salts,
preferably the compounds which are tri-, in particular tetra-substituted, and are preferably substituted in the 1-, 2-, 4- and 6-positions and have a substituent in the 3-position in the indole ring,
show a pharmacological effect and can be used as pharmaceuticals or for the production of pharmaceutical formulations.

The following may preferably be mentioned as heterocycles in the definition of R ⁶ , R ⁸ or R ¹⁰ :
A 5- to 10-membered saturated, partially unsaturated or aromatic, optionally benzo-fused heterocycle with up to 4 heteroatoms from the series S, N and / or O, ie a heterocycle which can contain one or more double bonds and which has a ring carbon atom or a ring stick material atom is linked. Examples include: tetrahydrofuryl, pyrrolidinyl, pyrrolinyl, piperidinyl, 1,2-dihydropyridinyl, 1,4-dihydropyridinyl, piperazinyl, morpholinyl, azepinyl, 1,4-diazepinyl, furanyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, triazolyl Tetrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrimidinonyl, pyridazinonyl.

From this list, the following are preferred: pyridyl, pyrimidinyl, pyridazinyl, pyrimidinonyl, Pyridazinonyl and thienyl.

In the context of the invention, alkyl represents a straight-chain or branched Alkyl radical preferably having 1 to 15, 1 to 12, 1 to 10, 1 to 8, 1 to 6, 1 to 4 or 1 up to 3 carbon atoms. A straight-chain or branched alkyl radical is preferred with 1 to 3 carbon atoms. Examples and preferably are: Methyl, ethyl, n-propyl, isopropyl, n-, i-, s- or t-butyl, n-pentyl and n-hexyl.

In the context of the invention, aryl stands for an aromatic radical with preferably 6 up to 10 carbon atoms. Preferred aryl radicals are phenyl and naphthyl.

Cycloalkyl is preferred in the context of the invention for a cycloalkyl group example, 3 to 8, 3 to 7 or 3 to 6 carbon atoms. Exemplary and preferred may be mentioned: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

Alkoxy preferably stands for a straight-chain or branched alkoxy radical having 1 to 6, 1 to 4 or 1 to 3 carbon atoms. before is a straight-chain or branched alkoxy radical with 1 to 3 carbon atoms. The following may be mentioned as examples and preferably: methoxy, ethoxy, n-propoxy, Isopropoxy, t-butoxy, n-pentoxy and n-hexoxy.

In the context of the invention, alkoxycarbonyl preferably represents a straight-chain one or branched alkoxy radical having 1 to 6 or 1 to 4 carbon atoms, which has a Carbonyl group is linked. A straight-chain or branched is preferred Alkoxycarbonylrest with 1 to 4 carbon atoms. Exemplary and preferred may be mentioned: methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxy carbonyl and t-butoxycarbonyl.  

Alkanoyloxy in the context of the invention is preferably a straight-chain or branched alkyl radical having 1 to 6, 1 to 5 or 1 to 3 carbon atoms, which in in the 1 position carries a double bonded oxygen atom and in the 1 position via another oxygen atom is linked. A straight-chain or ver is preferred branched alkanoyloxy radical having 1 to 3 carbon atoms. Exemplary and preferred Wise may be mentioned: acetoxy, propionoxy, n-butyroxy, i-butyroxy, pivaloyloxy and n-hexanoyloxy.

In the context of the invention, monoalkylamino represents an amino group with a straight-chain or branched alkyl substituents, which are preferably 1 to 6, 1 to 4 or has 1 to 2 carbon atoms. A straight-chain or ver is preferred branched monoalkylamino radical having 1 to 4 carbon atoms. Exemplary and preferably mentioned are: methylamino, ethylamino, n-propylamino, isopropyl amino, t-butylamino, n-pentylamino and n-hexylamino.

In the context of the invention, dialkylamino represents an amino group with two same or different straight-chain or branched alkyl substituents which preferably each have 1 to 6, 1 to 4 or 1 to 2 carbon atoms. Straight-chain or branched dialkylamino radicals each with 1 to 4 are preferred Carbon atoms. Examples include and are preferably: N, N-dimethyl amino, N, N-diethylamino, N-ethyl-N-methylamino, N-methyl-N-n-propylamino, N- Isopropyl-N-n-propylamino, N-t-butyl-N-methylamino, N-ethyl-N-n-pentylamino and N-n-hexyl-N-methylamino.

In the context of the invention, monoacylamino represents an amino group with a straight-chain or branched alkanoyl substituents, preferably 1 to 6, 1 has up to 4 or 1 or 2 carbon atoms and linked via the carbonyl group is. A monoacylamino radical having 1 to 2 carbon atoms is preferred. exemplary and preferably may be mentioned: formamido, acetamido, propionamido, n-butyr amido and pivaloylamido.  

In the context of the invention, alkoxycarbonylamino represents an amino group a straight-chain or branched alkoxycarbonyl substituent, the preferred example, has 1 to 6 or 1 to 4 carbon atoms in the alkoxy radical and via the Carbonyl group is linked. An alkoxycarbonylamino radical having 1 to 4 carbon atoms. Examples and preferably mentioned are: methoxycarbonyl amino, ethoxycarbonylamino, n-propoxycarbonylamino and t-butoxycarbonylamino.

Halogen in the context of the invention includes fluorine, chlorine, bromine and iodine. before fluorine, chlorine or bromine are added.

The compounds of the invention can, depending on the substituent tion patterns in stereoisomeric forms that are either like image and mirror image (Enantiomers), or which are not like image and mirror image (diastereomers) behave, exist. The invention relates to both the enantiomers or diastereo mer as well as their respective mixtures. The racemic shapes can also be used as the diastereomers in a known manner in the stereoisomerically uniform Separate components.

Furthermore, certain compounds can exist in tautomeric forms. This is known to those skilled in the art, and such compounds are also within the scope of Invention includes.

The compounds according to the invention can also be present as salts. As part of Physiologically acceptable salts are preferred according to the invention.

Physiologically acceptable salts can be salts of the compound according to the invention with inorganic or organic acids. Salts are preferred with inorganic acids such as hydrochloric acid, bromine water Substance acid, phosphoric acid or sulfuric acid, or salts with organic carbon or sulfonic acids such as acetic acid, propionic acid, maleic acid, fumaric acid,  Malic acid, citric acid, tartaric acid, lactic acid, benzoic acid, or methane sulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid or naphtha lindisulfonsäure.

Physiologically acceptable salts can also be salts of the invention Be compounds with bases, such as metal or ammonium salts. Preferred examples are alkali metal salts (e.g. sodium or potassium salts), earth alkali salts (e.g. magnesium or calcium salts), as well as ammonium salts, the abge are guided by ammonia or organic amines, such as ethylamine, Di- or triethylamine, ethyldiisopropylamine, monoethanolamine, di- or tri ethanolamine, dicyclohexylamine, dimethylaminoethanol, dibenzylamine, N-methyl morpholine, dihydroabietylamine, 1-ephenamine, methylpiperidine, arginine, lysine, Ethylenediamine or 2-phenylethylamine.

The compounds according to the invention can also be in the form of their solvates, in particular which are in the form of their hydrates.

The invention also includes prodrugs of the verb according to the invention fertilize. According to the invention, such derivatives of the compounds are called “prodrugs” of the general formula (I), which itself is less biologically active or can also be inactive, but after application under physiological conditions be converted into the corresponding biologically active form (for example wise metabolic, solvolytic or otherwise).

Compounds of the general formula (I) are preferred
in which
Z represents O, S or CH ₂ ,
R ¹ and R ^{2 are the} same or different and are hydrogen, fluorine, chlorine, bromine, (C ₁ -C ₄ ) alkyl, CF ₃ , CHF ₂ , CH ₂ F, vinyl or (C ₃ -C ₅ ) cycloalkyl are, where at least one of the two substituents is not hydrogen and is in the ortho position to the bridge bond, in particular both substituents are not hydrogen and both are in the ortho position,
R ³ for a group of the formula

A _m -D _n -E _o -G _p -LR ¹⁰

stands in what
A represents O, S, NR ¹¹ or the group - (CR ¹² = CR ¹³ ) -, in which R ¹¹ denotes hydrogen or methyl, and R ¹² and R ^{13 are} identical or different and denote hydrogen or methoxy,
D stands for a straight-chain (C ₁ -C ₃ ) alkylene group, which is mono- or divalent, identical or different, by (C ₁ -C ₄ ) alkyl, hydroxy, methoxy, ethoxy, fluorine, chlorine, amino, mono- (C ₁ -C ₄ ) alkylamino or mono- (C ₁ -C ₄ ) acylamino may be substituted,
E represents a C (O) group,
L represents a C (O) or SO ₂ group,
G represents an NH group or a straight-chain (C ₁ -C ₃ ) alkylene group which is mono- or disubstituted, identically or differently, by methyl, ethyl, hydroxy, methoxy, fluorine, chlorine, amino, methylamino or acetylamino can be,
m, n, o and p each independently stand for the number 0 or 1, with the proviso that in the case that L stands for a C = O group, the sum (m + n + o + p) is not equal the number is 0,
and
in the event that m and o each represent the number 1, A represents the radical NR ¹¹ and L represents a C = O group, the sum (n + p) is not equal to the number 0,
and
R ¹⁰ for OR ¹⁵ , NR ¹⁶ R ¹⁷ , (C ₁ -C ₆ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, naphthyl, phenyl, benzyl or for a saturated, partially unsaturated or aromatic 5- to 6- membered heterocycle with up to four identical or different heteroatoms from the series N, O and / or S, the abovementioned radicals optionally being selected from the group halogen, hydroxyl, oxo, cyano, nitro by one, two or three identical or different substituents , Amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ -C ₄ ) alkyl, optionally substituted by R ²⁰ (C ₁ -C ₄ ) alkoxy, (C ₃ -C ₆ ) cycloalkyl, -OC (O) -R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ -NR ²⁵ R ²⁶ , -NH-C (O) -R ²⁷ and -NH-C (O ) -OR ^{28 are} substituted, wherein
R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each represents hydrogen, Phenyl, benzyl, (C ₁ -C ₆ ) alkyl or (C ₃ -C ₆ ) cycloalkyl, which in turn are optionally one or more, identical or different, by halogen, hydroxyl, amino, carboxyl, (C ₁ - C ₄ ) -alkoxy, (C ₁ -C ₄ ) -alkoxycarbonyl, (C ₁ -C ₄ ) -alkoxy-carb onylamino, (C ₁ -C ₅ ) -alkanoyloxy, a heterocycle or optionally substituted by halogen or hydroxy-substituted phenyl are,
or
R ³ for a group of the formula

stands,
R ⁴ and R ^{5 are the} same or different and each represents hydrogen, halogen or (C ₁ -C ₄ ) alkyl,
R ^{6 represents} hydrogen, halogen or a group of the formula

-M _a -R ³²

stands in what
M represents a carbonyl group, a sulfonyl group or a methyl group,
a represents the number 0 or 1,
and
R ^{32 represents} (C ₁ -C ₁₀ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₄ ) alkenyl, naphthyl, phenyl, benzyl, pyridyl, pyridazinyl or pyridazinonyl, the aforementioned radicals optionally by one, two or three identical or different substituents selected from the group halogen, hydroxy, cyano, nitro, amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ -C ₄ ) alkyl, (C ₁ -C ₄ ) - Alkoxy, (C ₃ -C ₇ ) cycloalkyl, phenyl, which in turn is optionally substituted by halogen, (C ₁ -C ₄ ) alkyl, (C ₁ -C ₄ ) alkoxy, trifluoromethyl, nitro or cyano, -OC (O) - R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ -NR ²⁵ R ²⁶ , -NH-C (O) -R ²⁷ and -NH- C (O) -OR ^{28 are} substituted, wherein
R ¹⁸ , R ¹⁹ , R ²¹ , R ²² R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each is hydrogen, phenyl, benzyl, (C ₁ -C ₆ ) alkyl or (C ₃ -C ₆ ) cycloalkyl, which in turn are optionally one or more, identical or different, by halogen, hydroxy, amino, carboxyl, (C ₁ -C ₄ ) alkoxy, (C ₁ -C ₄ ) Alkoxycarbonyl, (C ₁ -C ₄ ) alkoxycarbonylamino, (C ₁ - C ₅ ) alkanoyloxy, a heterocycle or phenyl which is optionally substituted by halogen or hydroxy,
R ^{7 represents} hydrogen,
and
R ^{8 has} the meaning of R ⁶ given above and can be identical or different with this substituent,
and their pharmaceutically acceptable salts, solvates, hydrates and hydrates of the salts.

Compounds of the general formula (I) are particularly preferred
in which
Z represents O or CH ₂ ,
R ¹ and R ^{2 are the} same or different and are hydrogen, fluorine, chlorine, bromine, (C ₁ -C ₄ ) alkyl, CF ₃ , CHF ₂ , CH ₂ F, vinyl or (C ₃ -C ₅ ) cycloalkyl are, where at least one of the two substituents is not hydrogen and is in the ortho position to the bridge bond, in particular both substituents are not hydrogen and both are in the ortho position,
R ³ for a group of the formula

-A _m -D _n -E _o -G _p -LR ¹⁰

stands in what
A represents O, S or NH,
D represents a straight-chain (C ₁ -C ₃ ) alkylene group which can be substituted once or twice, identically or differently, by methyl, ethyl, hydroxy, methoxy, fluorine, amino or acetylamino,
E represents a C (O) group,
L represents a C (O) or SO ₂ group,
G represents an NH group or a methylene group,
m, n, o and p each independently represent the number 0 or 1, with the proviso that
in the event that L stands for a C = O group, the sum (m + n + o + p) is not equal to the number 0,
and
in the event that m and o each represent the number 1, A represents the remainder NH and L represents a C = O group, the sum (n + p) is not equal to the number 0,
and
R ¹⁰ for OR ¹⁵ , NR ¹⁶ R ¹⁷ , (C ₁ -C ₆ ) alkyl, phenyl, benzyl or for an aromatic 5- to 6-membered heterocycle with up to four identical or different heteroatoms from the series N, O and / or S, where the abovementioned radicals are optionally selected from the group fluorine, chlorine, hydroxyl, oxo, cyano, nitro, amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ -C. ₎ by one, two or three identical or different substituents ₄ ) alkyl, optionally substituted by R ²⁰ (C ₁ -C ₄ ) alkoxy, (C ₃ -C ₆ ) cycloalkyl, -OC (O) -R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ -NR ²⁵ R ²⁶ , -NH-C (O) -R ²⁷ and -NH-C (O) -OR ^{28 are} substituted, wherein
R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each represents hydrogen, Phenyl, benzyl, (C ₁ -C ₆ ) alkyl or (C ₃ -C ₆ ) cycloalkyl, which in turn are optionally one to two times, identical or different, by fluorine, chlorine, hydroxy, amino, carboxyl, (C ₁ -C ₄ ) alkoxy, (C ₁ -C ₄ ) alkoxycarbonyl, (C ₁ -C ₄ ) alkoxy carbonylamino, (C ₁ -C ₅ ) alkanoyloxy, a heterocycle or optionally substituted by fluorine, chlorine or hydroxy Phenyl are substituted,
R ⁴ and R ^{5 are the} same or different and each represents hydrogen, fluorine, chlorine or methyl,
R ^{6 represents} hydrogen, halogen or a group of the formula

-M _a -R ³²

stands in what
M represents a sulfonyl group or a methylene group,
a represents the number 0 or 1,
and
R ^{32 represents} (C ₁ -C ₁₀ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, phenyl, benzyl, pyridyl, pyridazinyl or pyridazinonyl, where the abovementioned radicals are selected from one or two identical or different substituents from the group fluorine, chlorine, bromine, hydroxy, cyano, nitro, amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ -C ₄ ) alkyl, (C ₁ - C ₄ ) alkoxy, (C ₃ -C ₇ ) -Cycloalkyl, -OC (O) -R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ -NR ²⁵ R ²⁶ -NH-C (O) -R ²⁷ and -NH-C (O) -OR ^{28 are} substituted, wherein
R ¹⁸ , R ¹⁹ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each represents hydrogen, phenyl, benzyl, (C ₁ -C ₆ ) - Are alkyl or (C ₃ -C ₆ ) cycloalkyl, which in turn are optionally mono- or discrete, identical or different, by fluorine, chlorine, hydroxyl, amino, carboxyl, (C ₁ -C ₄ ) alkoxy, (C ₁ - C ₄ ) alkoxycarbonyl, (C ₁ -C ₄ ) alkoxycarbonyl amino, (C ₁ -C ₅ ) alkanoyloxy, a heterocycle or optionally substituted by fluorine, chlorine or hydroxy-substituted phenyl,
R ^{7 represents} hydrogen,
R ^{8 represents} hydrogen, carboxyl, (C ₁ -C ₄ ) alkoxycarbonyl, (C ₁ -C ₆ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, phenyl, benzyl, pyridyl, phenylsulfonyl or benzylsulfonyl, where the the aforementioned radicals optionally by one or two identical or different substituents selected from the group fluorine, chlorine, bromine, hydroxy, cyano, nitro, amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ - C ₄ ) -alkyl, (C ₁ - C ₄ ) alkoxy, (C ₃ -C ₆ ) cycloalkyl, -OC (O) -R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ -NR ²⁵ R ²⁶ , -NH-C (O) -R ²⁷ and -NH-C (O) -OR ²⁸ are substituted, whereby
R ¹⁸ , R ¹⁹ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each represents hydrogen, phenyl, benzyl, (C ₁ -C ₆ ) - Alkyl or (C ₃ - C ₆ ) -cycloalkyl, which in turn are optionally one or more times, identical or different, by fluorine, chlorine, hydroxy, amino, carboxyl, (C ₁ -C ₄ ) alkoxy, (C ₁ -C ₄ ) -alkoxycarbonyl, (C ₁ -C ₄ ) -alkoxy carbonylamino, (C ₁ -C ₅ ) -alkanoyloxy, a heterocycle or optionally substituted by fluorine, chlorine or hydroxy-substituted phenyl,
and their pharmaceutically acceptable salts, solvates, hydrates and hydrates of the salts.

Compounds of the general formula are very particularly preferred. (I)
in which
Z stands for O,
R ¹ and R ^{2 are the} same or different and are hydrogen, fluorine, chlorine, bromine, (C ₁ -C ₄ ) alkyl, CF ₃ , CHF ₂ , CH ₂ F, vinyl or (C ₃ -C ₅ ) cycloalkyl are, where at least one of the two substituents is not hydrogen and is in the ortho position to the bridge bond, in particular both substituents are not hydrogen and both are in the ortho position,
R ³ for a group of the formula

-A _m -D _n -E _o -G _p -LR ¹⁰

stands in what
A represents O, S or NH,
D represents a methylene or ethylene group which can be substituted one to two times, identically or differently, by methyl, ethyl, fluorine, amino or acetylamino,
E represents a C (O) group,
L represents a C (O) or SO ₂ group,
G represents an NH group or a methylene group,
m, n, o and p each independently represent the number 0 or 1, with the proviso that
in the event that L stands for a C = O group, the sum (m + n + o + p) is not equal to the number 0,
and
in the event that m and o each represent the number 1, A represents the remainder NH and L represents a C = O group, the sum (n + p) is not equal to the number 0,
and
R ^{10 represents} OR ¹⁵ , NR ¹⁶ R ¹⁷ or (C ₁ -C ₄ ) alkyl, where R ¹⁵ , R ¹⁶ and R ^{17 are the} same or different and each represents hydrogen, phenyl, benzyl, (C ₁ -C ₆ ) -alkyl or (C ₃ -C ₆ ) -cycloalkyl, which in turn are optionally one or two times, identical or different, by fluorine, chlorine, hydroxy, amino, carboxyl, (C ₁ -C ₄ ) -alkoxy, ( C ₁ -C ₄ ) alkoxycarbonyl, (C ₁ -C ₄ ) alkoxycarbonylamino, (C ₁ -C ₅ ) alkanoyl oxy, a heterocycle or phenyl,
R ⁴ and R ^{5 are the} same or different and each represents hydrogen, fluorine, chlorine or methyl,
R ^{6 represents} hydrogen, halogen, (C ₁ -C ₁₀ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, (C ₃ -C ₇ ) cyclo alkylmethyl, phenyl, benzyl, pyridazinonylmethyl, phenylsulfonyl or pyridylsulfonyl, where the aforementioned aromatic radicals are optionally substituted by one or two identical or different substituents selected from the group consisting of fluorine, chlorine, cyano, nitro, trifluoromethyl, methyl, methoxy, carboxyl or methoxycarbonyl,
R ^{7 represents} hydrogen,
R ^{8 represents} hydrogen, (C ₁ -C ₆ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, phenyl, benzyl, phenyl sulfonyl or benzylsulfonyl, the aforementioned aromatic radicals optionally being selected by one or two identical or different substituents from the group fluorine, chlorine, cyano, trifluoromethyl, methyl or methoxy are substituted,
and their pharmaceutically acceptable salts, solvates, hydrates and hydrates of the salts.

Of particular importance are compounds of the general formula (I) in which
Z represents CH ₂ or in particular oxygen,
R ¹ and R ^{2 are} identical or different and represent methyl, ethyl, propyl, isopropyl, chlorine, bromine, CF ₃ , vinyl or cyclopropyl, both substituents being in the ortho position to the bridge bond,
R ⁴ and R ⁵ independently of one another represent methyl, fluorine or chlorine or in particular hydrogen,
and
R ^{7 represents} hydrogen.

The radicals listed above or specified in preferred ranges definitions apply both to the end products of the formula (I) and correspondingly for the raw materials or intermediate products required for the production.

Those in the respective combinations or preferred combinations of residues radical definitions specified in detail are independent of the respective specified combinations of the residues arbitrarily also by residue definitions and others rer combinations replaced.  

Compounds of the formula (I) in which Z is oxygen are particularly preferred stands.

Compounds of the formula (I) in which R ^{3 is} a group of the formula are particularly preferred

which is in the para position to the bridge bond and in which R ¹⁰ stands for hydroxy or the radical -C (O) -R ^{10 has} the meanings given for R ¹⁰ for a group which, in the sense of a prodrug to the carboxylic acid -C ( O) -OH or their salts can be broken down.

Compounds of the formula (I) in which R ⁴ , R ⁵ and R ^{7 are} hydrogen are particularly preferred.

Compounds of the formula (I) in which R ¹ and R ^{2 are} both arranged in the ortho position to Z and are bromine, trifluoromethyl, ethyl, cyclopropyl and in particular methyl or chlorine are particularly preferred.

Compounds of the formula (Ia) are very particularly preferred

in which
R ^{3 represents} a group of the formula -CH ₂ -C (O) -OH, -CHF-C (O) -OH or -CF ₂ -C (O) -OH,
and
R ^{6 is} their straight-chain or branched (C ₁ -C ₈ ) alkyl
stands.

Likewise, very particular preference is given to compounds of the formula (Ib)

in which
R ¹ and R ^{2 are} identical or different and represent bromine, trifluoromethyl, ethyl, cyclopropyl and in particular methyl or chlorine,
R ^{3 represents} a group of the formula -NH-C (O) -CH ₂ -C (O) -R ¹⁰ , wherein
R ¹⁰ stands for hydroxy or the radical -C (O) -R ^{10 has} the meanings given above of R ¹⁰ for a group which can be degraded as a prodrug to the carboxylic acid -C (O) -OH or its salts,
and
R ⁶ for straight-chain or branched (C ₁ -C ₈ ) alkyl
stands.

The following individual compounds are mentioned by way of example and preferably:
Compounds of the formula 1 in which R ^{3 has} the meanings given in Table 1 (* in the table means the point of attachment):

Table 1

Individual compounds of formula 2 in which R ³ each has the meanings given in Table 1 and R ² instead of methyl from Formula 1 for each of the individual compounds 1 to 35 each has the meanings given in Table 2 for R ² :

Table 2

Individual compounds of formula 3, in which R ² and R ³ each have the meanings given in Tables 1 and 2 and R ¹ instead of methyl from formula 2 for each of the individual compounds 1 to 490 each have the meanings given in Table 3 for R ¹ has:

Table 3

Individual compounds of the formula 4 in which R ¹ , R ² and R ³ each have the meanings given in Tables 1, 2 and 3 and R ⁶ instead of methyl from the formula 3 for each of the individual compounds 1 to 6860 each in the table 4 given meanings for R ⁶ has:

Table 4

The compounds of the general formula (I) according to the invention can be prepared by reacting reactive indole derivatives of the general formula (II) with reactive phenyl derivatives of the general formula (III)

wherein the substituents R ¹ , R ² , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ^{8 have} the meanings given above, and
R ^{3 'has} the meaning given for R ³ or for NO ₂ , NH ₂ , NH-PG, OH, O-PG, SH, S-PG, or for an aldehyde, cyano, carboxyl or (C ₁ - C ₄ ) alkoxy carbonyl group,
where PG stands for a protective group,
X and Y each represent groups of opposite reactivity, z. B. X can be an electrophilic radical which reacts with a nucleophilic Y substituent and vice versa,
Z 'has the meaning given for Z or represents CH-OH or C = O,
if appropriate in the presence of inert solvents and catalysts and if appropriate with isolation of the intermediates of the general formula (IV) or directly to give compounds of the formula (I).

Examples of catalysts are coupling catalysts such as Pd, Rh and / or Called Cu compounds.

The following may be mentioned as examples of the reactive groups X and Y: halogen, hydroxy, CH ₂ Br, mercapto, amino, CHO, Li, magnesium, tin or boron derivatives.

The indoles of the general formula (II) which can be used according to the invention are known or can be produced by known methods [compare e.g. B. Ozaki et al., Heterocycles 51, 727-731 (1999); Harvey et al., J. Chem. Soc., 473 (1959); Quadbeck et al., Hoppe-Seyler's Z. Physiolog. Chem. 297, 229 (1954); Chen et al., J. Org. Chem. 59, 3738 (1994); Synthesis, 480 (1988); J. Prakt. Chem. 340, 608 (1998)].

The phenyl derivatives of the general formula (III) are also known or can NEN are manufactured by known methods [compare z. B. from Bunt, Recl. Trav. Chim. Pays-Bas 48, 131 (1929); Valkanas, J. Chem. Soc., 5554 (1963)].

The reaction of the starting compounds (II) with (III) generally proceeds Normal pressure. But it can also go through under increased or reduced pressure leads.

The reaction can be in a temperature range from -100 ° C to 200 ° C, preferably performed between -78 ° C and 150 ° C in the presence of inert solvents  become. The following may be mentioned as inert solvents: dimethyl sulfoxide (DMSO), dimethylformamide (DMF), N methyl-2-pyrrolidinone (NMP), tetrahydro furan (THF), diethyl ether, dichloromethane etc.

Depending on the specific substituent pattern, intermediates of the formula (IV) can also arise in the reaction of (II) and (III), in which, for. B. the substituent R ^{3 'represents} a nitro, aldehyde, cyano, carboxyl or alkoxycarbonyl group or Z' represents a CHOH or C (O) group, which then with or without isolation of these intermediates usual methods to compounds of formula (I) are further implemented.

The method according to the invention can be exemplified by the following formula schemes are explained:

Process variant (A)

Process variant (B)

Process variant (C)

Depending on the meaning of the substituents R ¹ , R ² , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁸ , it may be expedient or necessary to vary them in the scope of the meaning given on individual process stages.

Protective groups (PG) are used in the present application such groups are understood in starting, intermediate and / or end products, the functional groups present such. B. carboxyl, amino, mercapto or Protect hydroxy groups and those common in preparative organic chemistry are. The groups protected in this way can then be known in a simple manner Conditions can be converted into free functional groups.

The compounds of formula (I) according to the invention show a surprising and valuable spectrum of pharmacological effects and can therefore be used as a variety use any medication. In particular, they can be used for all indications put that can be treated with natural thyroid hormones, such as exemplary and preferably depression, goiter or thyroid cancer. Prefers can be treated with the compounds of formula (I) according to the invention atherosclerosis, Treat hypercholesterolemia and dyslipidemia. Beyond that too Treat obesity and heart failure and one Achieve postprandial reduction in triglycerides.

The compounds are also suitable for the treatment of certain respiratory cranes kung and especially from emphysema and medication pulmonary maturation.

The compounds are also suitable for the treatment of pain conditions and Migraines, for neuronal repair (remyelination) and for the treatment of Alzheimer's disease.  

The compounds are also suitable for the treatment of osteoporosis, heart rhythm disturbances, hypothyroidisms and skin diseases.

The connections can also be used to promote and regenerate the Use hair growth and to treat diabetes.

The active substances according to the invention open up a further treatment alternative and represent an enrichment of pharmacy. In comparison to the known and Thyroid hormone preparations used to date show the inventive Connections an improved spectrum of activity. They prefer to excel due to great specificity, good tolerance and fewer side effects especially in the cardiovascular area.

The effectiveness of the compounds according to the invention can, for. B. Check in vitro using the T3 promoter assay cell test described below:
The test is carried out with a stably transfected human HepG2 hepatocarcinoma cell which expresses a luciferase gene under the control of a thyroid hormone-regulated promoter. The vector used for transfection carries a minimal thymidine kinase promoter with a thyroid hormone responsive element (TRE), which consists of two inverted palindromes of 12 bp each and an 8 bp spacer, in front of the luciferase gene.

For the test, the cell cultures are sown in 96-well plates in Eagle's Minimal Essential Medium with the following additives: glutamine, tricine [N- (tris (hydroxy methyl) methyl) glycine], sodium pyruvate, non-essential amino acids (L-Ala , L-Asn, L-Asp, L-Pro, L-Ser, L-Glu, Gly), insulin, selenium and transferrin. The cultures are grown for 48 hours at 37 ° C. and 10% CO ₂ atmosphere. Serial dilutions of test substance or reference compound (T3, T4) and costimulator retinoic acid are then added to the test cultures and these are incubated for a further 48 or 72 hours as before. Each substance concentration is tested in four replicates. To determine the luciferase induced by T3 or other substances, the cells are then lysed by adding a buffer containing Triton and Luciferin (from Promega) and immediately measured luminometrically. The EC ₅₀ values of each connection are calculated. Representative results for the compounds according to the invention are shown in Table 5:

Table 5

The compounds according to the invention also show surprisingly advantageous properties in the tests described below:
Test descriptions for the detection of pharmacologically active substances:
The substances that are to be examined for their serum cholesterol-lowering effect in vivo are administered orally to male mice with a body weight between 25 and 35 g. The animals are divided into groups with the same number of animals, usually n = 7-10, one day before the start of the experiment. During the entire experiment, drinking water and feed are available to the animals ad libitum. The substances are administered orally once a day for 7 days. For this purpose, the test substances are, for example, in a solution of Solutol HS 15 + ethanol + saline (0.9%) in a ratio of 1 + 1 + 8 or in a solution of Solutol HS 15 + saline (0.9%) in a ratio of 2 + 8 solved. The dissolved substances are applied in a volume of 10 ml / kg body weight with a gavage. Animals that are treated in the same way but only receive the solvent (10 ml / kg body weight) without test substance serve as a control group.

Before the first substance application, each mouse is used to determine the serum Cholesterol blood drawn by puncturing the retroorbital venous plexus (Pre value). The animals are then given the test substance with a pharyngeal tube administered the first time. 24 hours after the last substance application, (on the 8th day after the start of treatment), each animal is used to determine the serum cholesterol Blood was drawn again by puncturing the retroorbital venous plexus. The blood Samples are centrifuged and after the serum is obtained, the cholesterol photometric with an EPOS Analyzer 5050 (Eppendorf-Gerätebau, Netheler & Hinz GmbH, Hamburg). The determination is made with a commercial standard Chen enzyme test (Boehringer Mannheim, Mannheim).

The effect of the test substances on the serum cholesterol concentration is determined by Subtraction of the cholesterol value of the 1st blood sample (pre-value) from the cholesterol rin value of the 2nd blood sample (after treatment) determined. There are differences All cholesterol values in a group averaged and with the mean of the differences boundaries of the control group compared.

Statistical evaluation is carried out with Student's t-test after prior checking of variances on homogeneity.

Substances that compared the serum cholesterol of the treated animals with that of the Control group, decrease statistically significant (p <0.05) by at least 10%, are considered pharmacologically active.

At the end of the experiment, the animals are weighed and killed after the blood is drawn. To check for potential cardiovascular side effects under substance The hearts are removed and weighed under influence. An effect on the heart  Circulatory system can be determined by a significant increase in heart weight be put. A body can be another parameter for the substance effect weight change can be used.

In an analogous manner, e.g. B. NMRI mice, whether, whether mice, Wistar rats or fa, fa sugar rats are used as test animals for this test.

Another in vivo test in which the compounds of the invention are based on The animal model of cholesterol gene shows surprisingly beneficial properties fed rat [A. Taylor et al., Molecular Pharmacology 52, 542-547 (1997); Z. Stephan et al., Atherosclerosis 126, 53-63 (1996)].

Furthermore, the cholesterol-lowering effect of the verbin according to the invention also on normocholesterolemic dogs by oral administration of the test sub punches can be checked for 5-7 days.

For further investigation of potential cardiovascular side effects under Substance influence can include determining the expression of the mRNA of the "HCN2" ion channel ("hyperpolarization-activated cyclic nucleotide-gated channel") be used in mouse or rat hearts [cf. also: Trost et al., Endocrinology 141 (9), 3057-3064 (2000); Gloss et al., Endocrinology 142 (2), 544- 550 (2001); Pachuki et al., Circulation Research 85, 498-503 (1999)]:

HCN2 assay

The quantification of the mRNA of the "hyperpolarization-activated cyclic nucleotide- gated "cation channel (HCN2) in rat hearts was carried out by real-time PCR (TaqMan PCR; Heid et al., Genome Res. 6 (10), 986-994). For this, after Preparation of the hearts the total RNA using RNaesy columns (from Qiagen) isolated, digested with DNase and then rewritten into cDNA (SUPERSCRIPT-II RT cDNA synthesis kit, Gibco). The HCN2 mRNA  Determination is carried out on an ABI Prism 7700 device (from Applied Biosystems). The Sequence of the "forward" and "reverse" primer was: 5'- GGGAATCGACTCCGAGGTC-3 'or 5'-GATCTTGGTGAAACGCACGA-3', that of the fluorescent sample 5'-6FAM-ACAAGACGGCCCGTGCACTACGC- TAMRA-3 (FAM = fluorescent dye 6-carboxyfluorescein; TAMRA = Quencher 6-carboxytetramethylrhodamine). During the polymerase chain reaction becomes the fluorescent dye by the 5'-exonuclease activity of Taq polymerase Cleaved FAM and thereby received the previously quenched fluorescence signal. The so-called "threshold cyle" (Ct value) is the number of cycles at which the Fluorescence intensity 10 standard deviations above the background fluorescence was. The relative expression of the HCN2 mRNA calculated in this way is displayed then normalized to the expression of the ribosomal protein L32.

This assay can also be carried out in an analogous manner with mouse hearts. The sequence of the "forward" and "reverse" primers in this case was 5'- CGAGGTGCTGGAGGAATACC-3 'or 5'-CTAGCCGGTCAATAGCCACAG- 3 'that of the fluorescent sample 5'-6FAM-CATGATGCGGCGTGCCTTTGAG- TAMRA-third

For the application of the compounds of the general formula (I) all usual Chen application forms into consideration, d. H. also oral, parenteral, inhalative, nasal, sub lingual, buccal, rectal or external, e.g. B. transdermal, particularly preferred orally or parenterally. In parenteral administration, intravenous, To name intramuscular, subcutaneous application, e.g. B. as a subcutaneous depot. All Oral application is particularly preferred.

In particular, compounds of the general formulas (Ia) and (Ib) have surprisingly beneficial pharmacokinetic properties after oral administration, for example with regard to the bioavailability, the active ingredient concentration in the Blood, half-life and / or excretion rate.  

The active ingredients can be administered alone or in the form of preparations become. For oral application are suitable as preparations u. a. Tablets, chap seln, pellets, dragees, pills, granules, solid and liquid aerosols, syrups, emuls sions, suspensions and solutions. Here, the active ingredient in such a Amount present that a therapeutic effect is achieved. In general can the active ingredient in a concentration of 0.1 to 100 wt .-%, in particular 0.5 up to 90% by weight, preferably 5 to 80% by weight. In particular, the Concentration of the active ingredient 0.5-90 wt .-%, d. H. the active ingredient should be in Amounts are available that are sufficient to give the specified dosage range to reach.

For this purpose, the active substances can be converted into the usual manner in a manner known per se Preparations are transferred. This is done using inert, not toxic, pharmaceutically suitable carriers, auxiliaries, solvents, Vehicles, emulsifiers and / or dispersants.

Examples of auxiliary substances are: water, non-toxic organic Solvents such as B. paraffins, vegetable oils (e.g. sesame oil), alcohols (e.g. Ethanol, glycerin), glycols (e.g. polyethylene glycol), solid carriers such as natural Liche or synthetic stone powder (e.g. talc or silicates), sugar (e.g. Milk sugar), emulsifier, dispersant (e.g. polyvinylpyrrolidone) and lubricant medium (e.g. magnesium sulfate).

In the case of oral administration, tablets can of course also contain additives like sodium citrate along with additives like starch, gelatin and the like Chen included. Aqueous preparations for oral administration can continue with flavor enhancers or colorants.

When administered orally, doses of 0.001 to 5 mg / kg, preferably 0.001 to 3 mg / kg body weight applied per 24 hours.  

The new active ingredients can be used alone and, if necessary, in combination with others ren active ingredients preferably from the group CETP inhibitors, antidiabetic agents, Antioxidants, cytostatics, calcium channel blockers, hypotensive agents, Thyroid hormones, inhibitors of HMG-CoA reductase, inhibitors of HMG-CoA Reductase gene expression, squalene synthesis inhibitors, ACAT inhibitors, by bleeding agents, platelet aggregation inhibitors, anticoagulants, Angiotensin II receptor antagonists, cholesterol absorption inhibitors, MTP-Inhi bittern, aldose reductase inhibitors, fibrates, niacin, anorectics, lipase Inhibitors and PPAR agonists are administered.

The following exemplary embodiments are intended to explain the invention by way of example ters without restricting the scope of protection.  

used abbreviations

TLC thin layer chromatography
DCI direct chemical ionization (for MS)
DMF N, N dimethylformamide
DMSO dimethyl sulfoxide
EI electron impact ionization (for MS)
HPLC high pressure, high performance liquid chromatography
conc. concentrated
MS mass spectroscopy
NMP N-methylpyrrolidinone
NMR nuclear magnetic resonance spectroscopy
R _f

Retention index (for DC)
R _t

Retention time (with HPLC)
THF tetrahydrofuran
aq. aqueous
Dec. decomposition

starting compounds

Example I

5- (2,6-dichloro-4-nitrophenoxy) -3-isopropyl-1H-indole

5 g of 5-hydroxy-3-isopropylindole are dissolved in 10 ml of THF and with 3.2 g of potassium tert-butoxide added. The reaction mixture is stirred for 20 minutes at room temperature temperature and removes the solvent in vacuo. The phenolate is in 10 ml DMF dissolved and added to 6.46 g of 1,2,6-trichloro-4-nitrobenzene in 10 ml of DMF at 0 ° C drips. The mixture is stirred at 0 ° C. for 30 minutes and the reaction mixture is slowly released Warm up room temperature. The reaction mixture is poured onto water, extra hiert with ethyl acetate, dries over sodium sulfate and removes the solvent in Vacuum. Chromatographic purification (cyclohexane / ethyl acetate) gives 663 mg 5- (2,6-dichloro-4-nitrophenoxy) -3-isopropyl-1H-indole.

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.30, d, 6H; 3.09, sept., 1H; 6.79, dd, 1H; 6.99, m, 2H; 7.31, s, 1H; 7.89, s, broad, 1H; 8.32, s, 2H.

Example II

5- (2-chloro-6-methyl-4-nitrophenoxy) -3-isopropyl-1H-indole

4.4 g of 5-hydroxy-3-isopropylindole are dissolved in 10 ml of THF and at room temperature 2.82 g of potassium tert-butoxide were added. Stir for 30 minutes in the room temperature and rotates. The phenolate is dissolved in DMF, at 0 ° C with 5.17 g of 1,2- Dichloro-4-nitro-5-methylbenzene were added and the mixture was stirred at 0 ° C. for 30 minutes. You stir 15 minutes at room temperature and then 1 hour at 50 ° C. You leave them Cool reaction mixture, pour on water, extract 2 times with ether and washes the combined organic phases twice with water. The watery phases are extracted with dichloromethane, the combined organic phases evaporated and the residue purified by chromatography (cyclohexane / ethyl acetate). 6.65 g of 5- (2-chloro-6-methyl-4-nitrophenoxy) -3-isopropyl-1H-indole are obtained.

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.28, d, 6H; 2.31, s, 3H; 3.07, sept., 1H; 6.75, dd, 1H; 6.92, m, 1H; 6.99, m, 1H; 7.29, s, 1H; 7.87, s, broad, 1H.

Example III

3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylaniline

500 mg of 5- (2-chloro-6-methyl-4-nitrophenoxy) -3-isopropyl-1H-indole (Example II) are suspended in 10 ml of ethanol and with 50 mg of palladium on activated carbon (10%) and hydrogenated at atmospheric pressure for 2 hours. Filter through diatomaceous earth, removes the solvent in vacuo and purifies the product by chroma topography (cyclohexane / ethyl acetate). 271 mg of 3-chloro-4 - [(3-isopropyl-1H indol-5-yl) oxy] -5-methylaniline.

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.29, d, 6H; 2.11, s, 3H; 3.07, sept., 1H; 3.61, s, broad, 2H; 6.50, dd, 1H; 6.66, dd, 1H; 6.78, dd, 1H; 6.94, d, 2H; 7.20, s, 1H; 7.25, m, 1H; 7.78, s, broad, 1H.

Example IV

3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] aniline

500 mg of 5- (2,6-dichloro-4-nitrophenoxy) -3-isopropyl-1H-indole (Example I) stirred with 6.18 g of tin (II) chloride dihydrate in 5 ml of NMP at 50 ° C for 17 hours. The Solvent is removed in vacuo and the residue is dissolved in ethyl acetate accepted. It is washed with saturated ammonium chloride solution and saturated Sodium chloride solution, dries the organic phase and removes the solution medium in vacuum. The product is precipitated with diethyl ether. By chromato graphic purification (cyclohexane / ethyl acetate) of the solid gives 174 mg 3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] aniline.

¹ H NMR (300 MHz, DMSO-d ₆ ): δ = 1.21, d, 6H; 2.95, sept., 1H; 5.56, s, 2H; 6.63, dd, 1H; 6.71, s, 2H; 6.75, m, 1H; 7.06, d, 1H; 7.24, d, 1H.

Example V

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-benzaldehyde

12.8 g (70.27 mmol) of 5-hydroxy-3-isopropyl-indole are dissolved in 275.8 ml of DMSO, 10.68 g (77.3 mmol) of potassium carbonate are added firmly, the mixture is stirred at room temperature for 10 minutes and then 19.43 g (70.27 mmol) of 3,5-bistrifluoromethyl-4-chlorobenzaldehyde were added in portions. After 3 hours of stirring at 50 ° C, the mixture is poured onto a mixture of 400 ml of ethyl acetate and 250 ml of saturated ammonium chloride solution. After phase separation, the aqueous phase is extracted again with ethyl acetate, the combined organic phases are washed twice with brine and dried over sodium sulfate. After the desiccant has been separated off and the solvent has been distilled off, the crude product is chromatographed on silica gel 60 (Merck 0.040-0.063 mm) using toluene.
Yield: 18.55 g (56.6%)
MS (DCI): 450 ([M + NH ₃ + NH ₄ ] ⁺ , 100%)
R _f : 0.75 (toluene: ethyl acetate = 8: 2)

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.25, d, 6H; 3.04, quin, 1H; 6.73, dd, 1H; 6.87, d, 1H; 6.96, d, 1H; 7.22, d, 1H; 7.85, broad s, 1H; 8.45, s, 2H; 10.11, s, 1H.

Example VI

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-benzyl alcohol

To a solution of 1.0 g (2.41 mmol) of aldehyde derivative from Example V in 20 ml of methanol is added 0.27 g (7.22 mmol) of sodium borohydride in 4 portions at room temperature and stirred for 1 hour. The reaction solution is then concentrated in half, 60 ml of water are added and the mixture is concentrated until methanol has evaporated completely. The aqueous phase is extracted three times with ethyl acetate, the combined organic phases are washed with sodium chloride solution, dried, concentrated and dried under high vacuum.
Yield: 0.996 g (96.8%)
MS (ESI): 418 ([M + H] ⁺ , 35%)
HPLC: R _t = 4.97 (97.7%)
0.5% HCIO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / minute; 210 nm

¹ H NMR (300 MHz, CDCl3): δ = 1.28, d, 6H; 1.96, t, 1H; 3.04, quin, 1H; 4.87, d, 2H; 6.72, dd, 1H; 6.8 5, d, 1H; 6.93, d, 1H; 7.2, d, 1H; 7.78, broad s, 1H; 7.94, s, 2H.

Example VII

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-benzyl bromide

1.273 g (3.02 mmol) of triphenylphosphine dibromide are added in portions to a solution of 0.97 g (2.32 mmol) of benzyl alcohol derivative from Example VI in 15 ml of acetonitrile and 0.3 ml (3.72 mmol) of pyridine at 0 ° C. After 15 minutes, the cooling bath is removed and the mixture is stirred at room temperature for 2 hours. The reaction solution is concentrated in vacuo, the residue is dissolved in a little toluene and purified by chromatography on silica gel 60 using toluene.
Yield: 611 mg (54.7%)
MS (EI): 481 ([M] ⁺ , 60%)
HPLC: R _t = 5.30 (80.7%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / minute; 210 nm

¹ H NMR (300 MHz, CDCl3): δ = 1.28, d, 6H; 3.06, quin, 1H; 4.56, s, 2H; 6.70, dd, 1H; 6.88, d, 1H; 6.95, d, 1H; 7.23, d, 1H; 7.8, broad s, 1H; 8.0, s, 2H.

Example VIII

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-phenylacetonitrile

72.9 mg (1.49 mmol) of sodium cyanide are added to a solution of 0.57 g (1.19 mmol) of benzyl bromide from Example VII in 3.5 ml of dimethylformamide and 0.38 ml of water and the mixture is stirred 60 minutes at 50 ° C. Then dimethyl formamide is distilled off, the concentrate is diluted with ethyl acetate and water, the aqueous phase is separated off and extracted again with ethyl acetate. The combined organic phases are washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product is purified on silica gel 60 using toluene / ethyl acetate (toluene, toluene / ethyl acetate = 18: 1 or 18: 1.5).
Yield: 374 mg (73.9%)
MS (EI): 426 ([M] ⁺ , 60%)
R _f : 0.51 (toluene: ethyl acetate = 9: 1)

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.28, d, 6H; 3.06, quin, 1H; 3.93, s, 2H; 6.72, dd, 1H; 6.84, d, 1H; 6.96, d, 1H; 7.23, d, 1H; 7.82, broad s, 1H; 7.9, s, 2H.

Example IX

tert-butyl (4-hydroxy-3,5-dimethylphenoxy) acetate

10 g of dimethylhydroquinone in 750 ml of a mixture of 40% DMF and 60% THF dissolved and mixed with 117 g of cesium carbonate. At -25 ° C 14.1 g Tert-butyl bromoacetate was added dropwise and the reaction mixture is 17 hours the stirred at room temperature. After adding 10 g of potassium carbonate Reaction mixture stirred for 24 hours at room temperature, poured onto water and extracted 2 times with ethyl acetate. The combined organic phases are with Washed NaCl solution, dried over sodium sulfate and the solvent in Vacuum removed. By chromatographic purification (cyclohexane / ethyl acetate) 1.27 g of tert-butyl (4-hydroxy-3,5-dimethylphenoxy) acetate are obtained.

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.42, s, 9H; 2.11, s, 6H; 4.47, s, 2H .; 6.48, s, 2H; 7.74, s, 1H.

Example X

5-bromo-3-isopropyl-1H-indole

10 g of bromophenylhydrazine hydrochloride are suspended in 50 ml of acetic acid and 3.85 g of 3-methylbutyraldehyde were added dropwise at 80 ° C. You stir it The reaction mixture was refluxed for 3 hours, allowed to cool and removed Solvent in a vacuum. It is taken up in ethyl acetate, extracted with water, extract the aqueous phase with ethyl acetate, wash the combined organic Phases with water and sodium carbonate solution, dries over sodium sulfate and removes the solvent in vacuo. Chromatographic purification (Cyclo hexane / ethyl acetate) gives 8.6 g of 5-bromo-3-isopropyl-1H-indole.

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.35, d, 6H; 3.15, sept., 1H; 6.96, d, 1H; 7.24, m, 2H; 7.77, d, 1H; 7.89, s, broad, 1H.

Example XI

5-Bromo-1- [tert-butyl (dimethyl) silyl] -3-isopropyl-1H-indole

Under argon, 0.50 g (12.6 mmol) of 60% sodium hydride on paraffin oil 20 ml THF submitted at room temperature. A solution of 2.0 g is added dropwise (8.40 mmol) 5-bromo-3-isopropyl-1H-indole (Example X) in 20 ml THF and stirred until gas evolution can no longer be seen. Then be 2.03 g (13.44 mmol) of tert-butyl (chloro) dimethylsilane were added dropwise. After a short reak precipitation falls out. The mixture is stirred for 3 hours at room temperature. 200 ml of water are added. The aqueous phase is washed twice with ethyl acetate extracted, the combined org. Phases dried and evaporated. The backlog will Chromatographed on silica gel (eluent: cyclohexane). 2.63 g (89%) are obtained. 5-Bromo-1- [tert-butyl (dimethyl) silyl] -3-isopropyl-1H-indole.

¹ H NMR (200 MHz, CDCl ₃ ): δ = 0.58, s, 6H; 0.89, s, 9H; 1.33, d, 6H; 3.12, sept. 99999 00070 552 001000280000000200012000285919988800040 0002010130830 00004 99880, 1H; 6.88, s, 1H; 7.20, dd, 1H; 7.32, d, 1H; 7.71, d, 1H.

Example XII

1- [tert-butyl (dimethyl) silyl] -3-isopropyl-1H-indol-5-yl-boronic acid

Under argon, 1.30 g (3.69 mmol) of 5-bromo-1- [tert-butyl (dimethyl) silyl] -3-iso propyl-1H-indole (Example XI) dissolved in 10 ml of THF at -78 ° C. You drip 2.50 ml (4.24 mmol) of a 1.6 N tert-butyllithium solution in n-hexane. You leave Stir at -78 ° C for 30 min. Then 1.70 ml (7.38 mmol) of Triiso are added dropwise propylborate too. The mixture is stirred at -78 ° C for 2 h. Then moved one with 4 ml of water. The aqueous phase is extracted three times with diethyl ether,  the united org. Phases dried and evaporated. The residue becomes chromato graphically cleaned (eluent: cyclohexane, cyclohexane / ethyl acetate 5: 1, 3: 1). you receives 0.68 g (58%) of 1- [tert-butyl (dimethyl) silyl] -3-isopropyl-1H-indol-5-yl-boron acid.

¹ H NMR (200 MHz, CDCl ₃ ): δ = 0.65, s, 6H; 0.93, s, 9H; 1.48, d, 6H; 3.37, sept., 1H; 6.93, s, 1H; 7.62, d, 1H; 8.08, d, 1H; 8.64, s, 1H.
MS (ESI): 318 (M + H).

Example XIII

tert-Butyl [4 - ({1- [tert-butyl (dimethyl) silyl] -3-isopropyl-1H-indol-5-yl} oxy) -3,5-di methylphenoxy] acetate

0.50 g (1.58 mmol) of 1- [tert-butyl (dimethyl) silyl] -3-isopropyl-1H- are suspended. indol-5-yl boronic acid (Example XII), 0.437 g (1.73 mmol) tert-butyl- (4-hydroxy- 3,5-dimethylphenoxy) acetate (Example IX), 0.286 g (1.58 mmol) copper (II) acetate and 0.50 g molecular sieve (4Å, powdered) in 10 ml dried dichloromethane. at 0.64 ml (7.88 mmol) of pyridine and 1.10 ml (7.88 mmol) are added dropwise at room temperature. Triethylamine. The mixture is stirred at room temperature overnight. to finally the mixture is filtered through silica gel and after with dichloromethane washed. The filtrate is concentrated and the residue is filtered through silica gel (Dichloromethane). 0.525 g (62%) of tert-butyl- [4 - ({1- [tert-butyl- (dimethyl) - silyl] -3-isopropyl-1H-indol-5-yl} oxy) -3,5-dimethylphenoxy] acetate.  

¹ H NMR (300 MHz, CDCl ₃ ): δ = 0.54, s, 6H; 0.89, s, 9H; 1.27, d, 6H; 1.50, s, 9H; 2.12, s, 6H; 3.01, sept., 1H; 4.50, s, 2H; 6.63, s, 3H; 6.83, dd, 2H; 7.29, d, 1H.

Example XIV

3-isopropyl-5- (4-nitro-2,6-dimethyl-phenoxy) -1H-indole

11.44 g (58.76 mmol) of 5-hydroxy-3-isopropyl-indole are dissolved in 350 ml of DMSO, 8.93 g (64.63 mmol) of potassium carbonate are added and then 9.94 g (58.76 mmol ) 3,5-Dimethyl-4-fluoronitrobenzene added. The reaction solution is stirred for 2 hours at 100 ° C. under argon. The mixture is then cooled to room temperature, 100 ml of ethyl acetate and 600 ml of H ₂ O are added; after phase separation, ethyl acetate is separated off and the aqueous phase is extracted twice with ethyl acetate. The combined organic phases are washed twice with brine, dried over sodium sulfate, filtered and evaporated to dryness. The residue is purified by chromatography on silica gel using cyclohexane / ethyl acetate (10: 1).
Yield: 11.96 g (62.8%)
MS (DCI): 342 ([M + NH ₄ ] ⁺ , 100%)
R _f : 0.26 (cyclohexane: ethyl acetate = 8: 2)

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.28 (d, 6H); 2.24 (s, 6H); 3.05 (quin, 1H); 6.72 (dd, 1H); 6.84 (d; 1H); 6.99 (d: 1H); 7.27 (d, 1H); 7.87 (s, 1H); 8.03 (s, 2H).

Example XV

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-dimethyl-phenylamine

11.95 g (36.85 mmol) of nitro compound from Example XIV are hydrogenated in 500 ml of methanol / ethanol mixture with 550 mg of palladium / activated carbon (10%) at 3 bar. It is filtered through diatomaceous earth, the solvent is removed in vacuo and the product is purified by chromatography (toluene / ethyl acetate).
Yield: 10.75 g (97.9%)
MS (DCI): 295 ([M + H] ⁺ , 100%)
R _f : 0.36 (toluene: ethyl acetate = 9: 1)
HPLC: R _t = 4.15 (98.9%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / min .; 210 nm

Example XVI

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-dichloro-benzaldehyde

Analogously to the procedure of Example V, 10.0 g (57.07 mmol) of 5-hydroxy-3-isopropyl alcohol are dissolved in 300 ml of DMSO, 8.68 g (62.77 mmol) of potassium carbonate are added, for 10 minutes at room temperature stirred and 11.95 g (57.07 mmol) of 4,5,6-trichlorobenzaldehyde added in portions and stirred for 2 hours at room temperature and 2 hours at 50 ° C. After quenching with ethyl acetate / ammonium chloride solution and silica gel chromatography using toluene, 12.01 g (85.4%) of the desired product are obtained.
MS (CI-POS): 348 ([M + H] ⁺ , 100%)
R ^f : 0.60 (toluene: ethyl acetate = 9: 1)

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.29 (d, 6H); 3.08 (quin, 1H); 6.78 (dd, 1H); 6.99 (dd, 2H); 7.27 (d, 1H); 7.85 (broad s, 1H); 7.92 (s, 2H); 9.95 (s, 1H).

Example XVII

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-dichlorobenzyl alcohol

The preparation is carried out in analogy to the procedure of Example VI from 5.0 g (12.2 mmol) of aldehyde derivative from Example XVI using 1.39 g (36.61 mmol) of sodium borohydride.
Yield: 4.62 g (100%)
MS (CI-POS): 350 ([M + H] ⁺ , 100%)
R _f : 0.16 (toluene: ethyl acetate = 9: 1)

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.29 (d, 6H); 1.83 (weak t, 1H); 3.08 (quin, 1H); 4.71 (d, 2H); 6.8 (dd, 1H); 6.95 (d. 1H); 6.99 (d, 1H); 7.23 (d, 1H); 7.42 (s, 2H); 7.82 (broad s, 1H).

Example XVIII

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-dichlorobenzyl bromide

Analogously to the procedure of Example VII, 4.8 g (12.66 mmol) of benzyl alcohol derivative from Example XVII with 6.95 g (16.46 mmol) of dibromotriphenylphosphorane and 1.6 g (20.26 mmol) of pyridine in 80 ml of acetonitrile implemented.
Yield: 2.03 g (35.5%)
MS (CI-POS): 413 ([M + H] ⁺ , 57%)
HPLC: R _t = 5.62 (91.4%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / min .; 210 nm

¹ H NMR (300 MHz, CDCl3): δ = 1.3 (d, 6H); 3.1 (quin, 1H); 4.43 (s, 2H); 6.77 (dd, 1H); 6.97 (s, 1H); 7.02 (d, 1H); 7.24 (d, 1H); 7.43 (s, 2H); 7.82 (broad s, 1H).

Example XIX

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-dichlorophenylacetonitrile

Analogously to the procedure of Example VIII, 1.0 g (2.42 mmol) of benzyl bromide from Example XVIII is mixed with 0.15 g (3.03 mmol) of sodium cyanide in DMF / H ₂ O (10: 1) at 50 ° C. in 60 Min. Implemented. After isolation of the crude product (distilling off DMF and quenching with ethyl acetate / water), chromatography on silica gel 60 is carried out using toluene.
Yield: 0.763 g (65.4%)
MS (DCI): 359 ([M + H] ⁺ , 67%)
R _f : 0.47 (toluene: ethyl acetate = 9: 1)

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.3 (d, 6H); 3.09 (quin, 1H); 3.78 (s, 2H); 6.78 (dd, 1H); 6.97 (d. 2H); 7.25 (d, 1H); 7.4 (s, 2H); 7.85 (broad s, 1H).

Example XX

4- (3-cyclohexylmethyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-benzaldehyde

Analogously to the procedure of Example V, 2.0 g (8.72 mmol) of 5-hydroxy-3-cyclohexylmethyl-indole are dissolved in 50 ml of DMSO, 1.33 g (9.59 mmol) of potassium carbonate are added, for 10 minutes Stirred at room temperature and then added 2.41 g (8.72 mmol) of 3,5-bistrifluoromethyl-4-chlorobenzaldehyde in portions. After stirring overnight at 50 ° C., the mixture is worked up analogously to Example V and the crude product is chromatographed on silica gel 60 using toluene.
Yield: 2.23 g (49.8%)
MS (DCI): 504 ([M + NH ₃ + NH ₄ ] ⁺ , 100%)
R _f : 0.57 (toluene: ethyl acetate = 9: 1)

¹ H NMR (300 MHz, CDCl ₃ ): δ = 0.91 (m, 2H); 1.15 (m, 4H); 1.5 (m, 1H); 1.66 (m, 4H); 2.5 (d, 2H); 6.71 (dd, 1H); 6.82 (d, 1H); 6.97 (d. 1H); 7.22 (d, 1H); 7.89 (broad s, 1H); 8.46 (s, 2H); 10.11 (s, 1H).

Example XXI

4- (3-cyclohexylmethyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-benzyl alcohol

The preparation is carried out in analogy to the procedure of Example VI from 2.20 g (4.29 mmol) of aldehyde derivative from Example XX with 0.49 g (12.86 mmol) of sodium borohydride.
Yield: 2.05 g (100%)
MS (ESI): 4.72 ([M + H] ⁺ , 100%)
HPLC: R _t = 5.34 (98.4%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / min .; 210 nm

¹ H NMR (200 MHz, CDCl ₃ ): δ = 0.9 (m, 2H); 1.13 (m, 4H); 1.5 (m, 1H); 1.63 (m, 4H); 1.95 (t, 1H); 2.5 (d, 2H); 4.88 (d. 2H); 6.7 (dd, 1H); 6.81 (d, 1H); 6.93 (d, 1H); 7.2 (d, 1H); 7.83 (broad s, 1H); 7.94 (s, 2H).

Example XXII

4- (3-cyclohexylmethyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-benzyl bromide

The preparation is carried out in analogy to the procedure of Example VII from 2.0 g (4.18 mmol) of benzyl alcohol derivative from Example XXI and 2.82 g (6.69 mmol) of di bromotriphenylphosphorane in 40 ml of acetonitrile. After 3 hours of stirring at room temperature, another 0.3 equivalents of dibromotriphenylphosphorane are added. The mixture is stirred for 5 hours at 70 ° C and then overnight at room temperature. The product is purified on silica gel using toluene as the eluent.
Yield: 0.96 g (40.2%)
MS (ESI): 534 ([M + H] ⁺ , 100%)
R _f : 0.76 (toluene: ethyl acetate = 9: 1)

¹ H NMR (200 MHz, CDCl ₃ ): δ = 0.92 (m, 2H); 1.16 (m, 4H); 1.5 (m, 1H); 1.66 (m, 4H); 2.5 (d, 2H); 4.58 (s, 2H); 6.69 (dd, 1H); 6.83 (d. 1H); 6.95 (d. 1H); 7.21 (d, 1H); 7.35 (broad s, 1H); 7.95 (s, 2H).

Example XXIII

4- (3-cyclohexylmethyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-phenylacetonitrile

The preparation is carried out analogously to the procedure of Example VIII from 0.85 g (1.59 mmol) of benzyl bromide from Example XXII with 0.1 g (1.99 mmol) of sodium cyanide in 5 ml of dimethylformamide and 0.5 ml of water at 50 ° C in 1.5 hours. The crude product is chromatographed on silica gel 60 using toluene.
Yield: 0.32 g (37.7%)
MS (ESI): 481 ([M + H] ⁺ , 100%)
HPLC: R _t = 5.67 (90.0%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / min .; 210 nm

¹ H NMR (300 MHz, CDCl ₃ ): δ = 0.92 (m, 2H); 1.16 (m, 4H); 1.5 (m, 1H); 1.67 (m, 4H); 2.5 (d, 2H); 3.92 (s, 2H); 6.69 (dd, 1H); 6.8 (d, 1H); 6.95 (d. 1H); 7.22 (d, 1H); 7.84 (broad s, 1H); 7.91 (s, 2H).

Preparation Examples

example 1

Methyl 3 - ({4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl]} amino) -3-oxo propanoate

0.2 g (0.68 mmol) of 4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylaniline (Example XV) are mixed in 2 ml of acetone with 76 mg (0, 75 mmol) of triethylamine are added and 102 mg (0.75 mmol) of methyl malonate are added at 0 ° C. The mixture is stirred for 1 h, diluted with dichloromethane and extracted with sodium chloride solution and with NaHCO ₃ solution. The organic phase is dried and the solvent is removed in vacuo. 211 mg (74%) of methyl 3 - ({4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} amino) -3-oxo-propanoate are obtained.

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.29, d, 6H; 2.16, s, 6H; 3.05, hept., 1H; 3.50, s, 2H; 3.81, s, 3H; 6.72, dd, 1H; 6.88, d, 1H; 6.95, d, 1H; 7.25, m, 1H; 7.30, s, 2H; 7.77, s, broad, 1H.

Example 2

3 - ({4 - [(3-Isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} amino) -3-oxopropanoic acid

50 mg methyl 3 - ({4 - [(3-sopropyl-1H-indol-5-yl) oxy] -3,5-dimethyl-phenyl} amino) - 3-oxo-propanoate (Example 1) in 30 ml of ethanol with 30 mg of sodium hydroxide 30 Minutes stirred. The solvent is removed in vacuo. You take in Ether / water, dries the organic phase and removes the solvent in the Vacuum. 23 mg (46%) of 3 - ({4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-di are obtained methylphenyl} amino) -3-oxopropanoic acid.

¹ H NMR (300 MHz, DMSO-d ₆ ): δ = 1.18, d, 6H; 2.02, s, 6H; 2.92, hept., 1H; 6.52, dd, 1H; 6.64, d, 1H; 7.02, s, 2H; 7.18, d, 1H; 7.32, s, 2H.

Example 3

Ethyl-N- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} glycinate

210 mg of 4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylaniline (Example XV) who with 119 mg of ethyl bromoacetate and 117 mg of sodium acetate in 10 ml  Ethanol refluxed for 24 h. After adding water, the mixture is washed with ether extracted, the organic phase dried and evaporated. By chromatographic Purification (cyclohexane / ethyl acetate) gives 143 mg (53%) of ethyl N- {4 - [(3- isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} glycinate.

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.27, d, 6H; 1.31, t, 3H; 2.09, s, 6H; 3.06, hept., 1H; 3.92, s, 2H; 4.12, s, broad, 1H; 4.26, quarter, 2H; 6.3 8, s, 2H; 6.72, dd, 1H; 6.91, dd, 2H; 7.20, d, 1H; 7.77, s, broad; 1H.

Example 4a

Methyl 3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxo-propanoate

131 mg 3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylaniline (Example III) are dissolved in 3 ml of acetone with 46 mg of triethylamine and with 62 mg of malonic acid methyl ester chloride was added dropwise at 0 ° C. Stir for 3 hours in the room temperature, pour the reaction mixture onto 20 ml dichloromethane, wash the organic phase with sodium chloride solution, dries over sodium sulfate and rotates. Obtained by chromatographic purification (cyclohexane / ethyl acetate) 134 mg of methyl 3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphen yl} amino) -3-oxo-propanoate.

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.28, d, 6H; 2.20, s, 3H; 3.07, sept., 1H; 3.50, s, 2H; 3.83, s, 3H; 6.77, dd, 1H; 6.92, d, 1H; 6.95, d, 1H; 7.24, m, 1H; 7.36, d, 1H; 7.65, d, 1H; 7.81, s, broad, 1H; 9.24, s, broad, 1H.

Example 4b

Ethyl 3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxo-propanoate

Analogously to Example 4a, starting from 2.50 g (7.94 mmol) of 3-chloro-4- [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylaniline (Example III) and 1.26 g (7.94 mmol) ethyl malonate 3.65 g (99% of theory) ethyl 3 - ({3-chloro-4- [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxo-propanoate.

¹ H NMR (200 MHz, CDCl ₃ ): δ = 1.28, d, 6H; 1.34, t, 3H; 2.19, s, 3H; 3.08, sept., 1H; 3.49, s, 2H; 4.27, quart., 2H; 6.76, dd, 1H; 6.93, m, 2H; 7.22, m, 1H; 7.36, d, 1H; 7.66, d, 1H; 7.80, broad s, 1H; 9.32, broad s, 1H.

Example 4c

Isopropyl 3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) - 3-oxo-propanoate

Starting from 3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] - 5-methylaniline (Example III) can be prepared in analogy to Example 4a.  

Example 4d

2-Hydroxyethyl-3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} - amino) -3-oxopropanoate

Starting from 3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] - 5-methylaniline (Example III) or methyl-3 - ({3-chloro-4 - [(3-isopropyl-1H-indole-5- yl) oxy] -5-methylphenyl} amino) -3-oxo-propanoate (Example 4a) according to literature known methods are produced.

Example 5

N- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} glycine

56 mg ethyl N- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} glycinate (Example 3) in 7 ml of dioxane with 1.5 ml of 1 N sodium hydroxide solution for 2 hours at room temperature stirred. The mixture is poured onto water, acidified with 1N hydrochloric acid and extracted with ethyl acetate, dries and removes the solvent in vacuo. You get 51 mg of N- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} glycine.  

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.29, d, 6H; 2.10, s, 6H; 3.07, sept., 1H; 3.70, s, 2H; 6.41, s, 2H; 6.73, m, 1H; 6.91, m, 2H; 7.21, d, 1H; 7.77, s, broad, 1K.

Example 6

3 - ({3-Chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxo propionic acid

101 mg methyl-3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} - amino) -3-oxo-propanoate (Example 4a) in 2 ml of ethanol and 1 ml of 1N sodium hydroxide lye dissolved, stirred at room temperature for 1 hour and the solvent in Vacuum removed. It is acidified, extracted with ethyl acetate and dried over Sodium sulfate and removes the solvent in vacuo. 87 mg 3 - ({3- Chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxopropion acid.

¹ H NMR (300 MHz, MeOH-d ₄ ): δ = 1.25, d, 6H; 2.16, s, 3H; 2.99, sept., 1H; 3.45, s, 2H; 6.69, dd, 1H; 6.76, d, 1H; 6.96, s, 1H; 7.23, d, 1H; 7.38, d, 1H; 7.73, d, 1H.

Example 6a

Potassium 3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxopropanoate

1.16 g (2.89 mmol) of 3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methyl phenyl} amino) -3-oxopropionic acid (Example 6) are dissolved in 15 ml of THF and at 5.7 ml of a 0.51 molar potassium hydroxide solution were added dropwise at 0 ° C. The reaction mixture is stirred for one hour and then the solvent in Vacuum removed. Co-evaporation with toluene gives 1.25 g (99% of theory) Potassium 3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3- oxopropanoate.

¹ H NMR (200 MHz, DMSO-d ₆ ): δ = 1.20, d, 6H; 2.10, s, 3H; 2.83, s, 2H; 2.96, sept., 1H; 6.62, dd, 1H; 6.73, d, 1H; 7.04, d, 1H; 7.26, m, 3H; 7.84, d, 1H; 10.70, s, broad, 1H; 13.03, s, broad, 1H.

Example 6b

Sodium 3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxopropanoate

This compound is obtained in a manner analogous to Example 6a, starting from 3 - ({3- Chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxopropion acid (Example 6) and sodium hydroxide.

Example 6c

Magnesium bis [3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} - amino) -3-oxopropanoate]

This compound is obtained in a manner analogous to Example 6a, starting from 3 - ({3- Chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxopropion acid (Example 6) and magnesium methanolate.

Example 6d

Calcium bis [3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} - amino) -3-oxopropanoate]

This compound is obtained in a manner analogous to Example 6a, starting from 3 - ({3- Chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxopropion acid (Example 6) and calcium hydroxide.  

Example 7

Methyl 3 - ({3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} amino) -3-oxopropanoate

139 mg of 3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] aniline (Example IV) with 46 mg triethylamine dissolved in 3 ml acetone and with 62 mg malonic acid methyl ester chloride added dropwise at 0 ° C. The mixture is stirred for 1 hour at room temperature, pouring the reaction mixture onto 20 ml dichloromethane, the organic phase washes with sodium chloride solution, dries over sodium sulfate and rotates. By chromatographic purification (cyclohexane / ethyl acetate) gives 162 mg of methyl 3 - ({3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} amino) -3-oxopropanoate.

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.29, d, 6H; 3.09, sept., 1H; 3.47, s, 2H; 3.82, s, 3H; 6.80, dd, 1H; 6.96, m, 1H; 7.19, s, 1H; 7.24, m, 1H; 7.70, s, 2H; 7.82, s, broad, 1H; 9.43, s, broad, 1H.

Example 8

3 - ({3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} amino) -3-oxopropionic acid

193 mg methyl-3 - ({3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} amino) -3- oxopropanoate (Example 7) in 3 ml of ethanol with 1 ml of 1N NaOH for one hour stirred at room temperature. The solvent is removed in vacuo and the Residue taken up in dichloromethane. You shake with water, dry it organic phase and removes the solvent in vacuo. By stirring with Diethyl ether gives 143 mg of 3 - ({3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] - phenyl} amino) -3-oxopropanoate.

¹ H NMR (300 MHz, MeOH-d ₄ ): δ = 1.27, d, 6H; 3.00, sept., 1H; 3.35, s, 2H; 6.70, dd, 1H; 6.79, m, 1H; 6.97, s, 1H; 7.23, d, 1H; 7.79, s, 2H.

Example 9

Ethyl N- {3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} glycinate

120 mg 3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylaniline (Example III) are mixed with 62 mg sodium acetate and 63 mg ethyl bromoacetate in 5 ml Ethanol heated to reflux for 17 hours. A further 21 mg of bromoacetic acid are added ethyl ester and refluxed for 3 hours. The solvent is removed in vacuo, one takes up with water and dichloromethane, the organic phase is washed with saturated sodium chloride solution, dries the organic phase and removes it Solvent in a vacuum. Chromatographic purification (cyclohexane / ethyl acetate) gives 56 mg of ethyl N- {3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methyl phenyl} glycinate.

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.29, d, 6H; 1.32, t, 3H; 2.13, s, 3H; 3.08, sept., 1H; 3.91, s, 2H; 4.28, fourth, 2H; 6.43, d, 1H; 6.56, d, 1H; 6.77, dd, 1H; 6.94, d, 1H; 7.22, d, 1H; 7.78, s, broad, 1H.

Example 10

Ethyl N- {3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} glycinate

100 mg of 3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] aniline (Example IV) with 49 mg sodium acetate and 50 mg ethyl bromoacetate in 5 ml ethanol 17 Heated at reflux for hours. A further 21 mg of ethyl bromoacetate are added and refluxed for 2 hours. The solvent is removed in vacuo, one takes with water and dichloromethane, the organic phase washes with saturated Sodium chloride solution, dries the organic phase and removes the solution medium in vacuum. Chromatographic purification (cyclohexane / ethyl acetate) results 22 mg of ethyl N- {3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} glycinate.

¹ H NMR (300 MHz, DMSO-d ₆ ): δ = 1.21, t, 3H; 1.22, d, 6H; 2.96, m 1H; 4.00, m, 2H; 4.15, quart., 2H; 6.63, m, 1H; 6.76, d, 1H; 6.77, s, 2H; 7.06, d, 1H; 7.24, d, 1H.

Example 11

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-phenylacetic acid

A solution of 5 ml of concentrated sulfuric acid and 5 ml of water is added dropwise to a solution of 0.35 g (0.82 mmol) of nitrile derivative from Example VIII in 5 ml of acetic acid (100%). The reaction solution is stirred for 4 hours at 105 ° C., then cooled to room temperature and mixed with ice-cold water and ethyl acetate. The organic phase is separated off, the aqueous solution is extracted again with ethyl acetate, the combined organic phases are dried over sodium sulfate, filtered and concentrated to an oil. The crude product (120.3 mg) is chromatographed on silica gel 60 using methylene chloride / methanol (95: 5 and 95: 11).
Yield: 55 mg (15.3%)
MS (DCI): 446 ([M + H] ⁺ , 100%)
R _f : 0.38 (methylene chloride: methanol = 9: 1)

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.28, d, 6H; 3.05, quin, 1H; 3.81, s, 2H; 6.69, dd, 1H; 6.89, d, 1H; 6.94, d, 1H; 7.21, d, 1H; 7.8, broad s, 1H; 7.88, s, 2H.

Example 12

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-benzyltetrazol

251 mg (4.69 mmol) of ammonium chloride and 305 mg (4.69 mmol) of sodium azide are added to a solution of 200 mg (0.469 mmol) of nitrile derivative from Example VIII in 8 ml of dimethylformamide and the mixture is boiled under reflux for 4 hours. The solution is then strongly concentrated, treated with 6 N hydrochloric acid and extracted three times with ethyl acetate. The combined organic phases are dried, filtered and concentrated in vacuo to an oil. The crude product is dissolved in dichloromethane and chromatographed on silica gel 60 with dichloromethane with the addition of methanol in the gradient mode (90: 5 to 90:40).
Yield: 126 mg (57.3%)
MS (ESI): 470 ([M + H] ⁺ , 100%)
R _f : 0.30 (dichloromethane: methanol = 9: 1)

¹ H NMR (200 MHz, CDCl ₃ ): δ = 1.27, d, 6H; 3.06, quin, 1H; 4.49, s, 2H; 6.67, dd, 1H; 6.88, d, 1H; 6.94, d, 1H; 7.2, d, 1H; 7.84, broad s, 1H; 7.92, s, 2H; 8.01, s, 1H.

Example 13

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-cinnamate

1.0 g (2.41 mmol) of aldehyde derivative from Example V is dissolved in 10 ml of toluene and 0.92 g (2.65 mmol) of ethoxycarbonylmethylene triphenylphosphorane is added in portions. After 2 days of stirring at room temperature, the reaction mixture is concentrated to half the volume and chromatographed on silica gel 60 using toluene.
Yield: 1.076 g (88.4%)
MS (ESI): 486 ([M + H] ⁺ , 100%)
R _f : 0.68 (toluene: ethyl acetate = 8: 2)
HPLC: R _t = 5.44 (94.5%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / minute; 210 nm

¹ H NMR (200 MHz, CDCl ₃ ): δ = 1.27, d, 6H; 1.37, t, 3H; 3.05, quin, 1H; 4.3, fourth, 2H; 6.55, broad d, 1H; 6.72, dd, 1H; 6.87, d, 1H; 6.95, d, 1H; 7.21; , d, 1H; 7.73, broad d, 1H; 7.84, broad s, 1H; 8.04, s, 2H.

Example 14

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-cinnamic acid

0.23 g (0.46 mmol) of ethyl cinnamate from Example 13 are dissolved in 10 ml of dioxane, 4 ml of 1 molar sodium hydroxide solution are added and the mixture is stirred at room temperature for 5 hours. The reaction solution is acidified to pH 4 with 1N hydrochloric acid, ethyl acetate is added and the aqueous phase is extracted twice with ethyl acetate. The combined organic phases are washed with sodium chloride solution, dried over sodium sulfate, filtered, concentrated and dried under high vacuum overnight.
Yield: 0.175 g (79.0%)
MS (DCI): 475 ([M + NH ₄ ] ⁺ , 100%)
HPLC: R _t = 4.99 (96.3%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / minute; 210 nm

¹ H NMR (200 MHz, CDCl ₃ ): δ = 1.28, d, 6H; 3.06, quin, 1H; 6.59, broad d, 1H; 6.73, dd, 1H; 6.88, d, 1H; 6.97, d, 1H; 7.23, d, 1H; 7.83, broad s and broad d, 2H; 8.09, s, 2H.

Example 15

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-phenylpropionic acid

150 mg (0.328 mmol) of cinnamic acid derivative from Example 14 are dissolved in 10 ml of methanol, 75 mg of palladium on activated carbon (10%) are added and the mixture is hydrogenated at hydrostatic hydrogen pressure for 18 hours. The palladium catalyst is filtered off with kieselguhr, washed with methanol and the filtrate is concentrated to a solid product.
Yield: 86.2 mg (57.2%)
MS (LC): 460 ([M + H] ⁺ , 100%)
R _f : 0.76 (methylene chloride: methanol = 10: 1)

¹ H NMR (200 MHz, DMSO-d ₆ ): δ = 1.19, d, 6H; 2.7, t, 2H; 2.95, quin, 1H; 3.03, t, 2H; 6.58, dd, 1H; 6.7, d, 1H; 7.08, d, 1H; 7.24, d, 1H; 8.05, s, 2H; 10.72, d, 1H; 12.25, broad s, 1H.

Example 16

{4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenoxy} acetic acid

0.24 g (0.46 mmol) of tert-butyl- [4 - ({1- [tert-butyl- (dimethyl) silyl] -3-isoprop yl-1H-indol-5-yl} oxy) -3,5-dimethylphenoxy] acetate (Example XIII) in 5 ml of ethanol dissolved and adds 2.5 ml (2.50 mmol) of 1 N sodium hydroxide solution. The approach is going Stirred for 2.5 h at room temperature. The solvent is spun off, the mixture with Diluted 50 ml of water and acidified with 1 N hydrochloric acid solution. The watery Phase is extracted twice with ethyl acetate, the combined organic phases are dried and the solvent is removed in vacuo. 0.186 g is obtained (87.3%) {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenoxy} acetic acid.

¹ H NMR (200 MHz, CDCl ₃ ): δ = 1.28, d, 6H; 2.10, s, 6H; 2.96, m, 1H; 3.08, sept., 1H; 4.58, s, 2H; 6.68, s, 3H; 6.90, dd, 2H; 7.81, s, 1H.

Example 17

4- (3-isopropyl-1H-indol-5-yloxy) -3,5-dichlorophenyl acetic acid

5 ml of conc. Are first added dropwise to a solution of 0.43 g (0.90 mmol) of nitrile derivative from Example XIX in 10 ml of dioxane. Add sulfuric acid and then 5 ml of water. The reaction mixture is stirred for 4 hours at 100 ° C., then poured onto ice and extracted twice with ethyl acetate. The combined organic phases are washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude product is chromatographed on silica gel 60 using toluene / ethyl acetate (1: 1) in the isocratic mode.
Yield: 0.266 g (68.7%)
MS (DCI): 395 ([M + NH ₄ ] ⁺ , 100%)
HPLC: R _t = 4.79 (87.8%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / min .; 210 nm

¹ H NMR (200 MHz, CDCl ₃ ): δ = 1.4 (d, 6H); 3.1 (quin, 1H); 3.65 (s, 2H); 6.76 (dd, 1H); 6.95 (d. 1H); 7.03 (d, 1H); 7.24 (d, 1H); 7.34 (s, 2H); 7.81 (broad s, 1H).

Example 18

5- {4 - [(3-Isopropyl-1H-indol-5-yl) oxy] -3,5-bis-trifluoromethylphenyl} imidazolidine-2,4-dione

3.0 g (7.22 mmol) of aldehyde from Example V dissolved in 30 ml of ethanol are added to a solution of 0.581 g (14.4 mmol) of sodium cyanide and 3.63 g (36.1 mmol) of ammonium carbonate in 30 ml of water added and stirred for 24 hours at 60 ° C. The reaction solution is then distilled off from ethanol, diluted with water, acidified to pH 2 with 1 N hydrochloric acid while cooling with ice and extracted twice with ethyl acetate. After drying and distilling off the solvent, the crude product (4.03 g) is chromatographed on silica gel 60 with methylene chloride with the addition of a little methanol in a ratio of 20: 1 to 20: 2.5.
Yield: 2.73 g (78.1%)
MS (ESI): 486 ([M + H] ⁺ , 100%)
HPLC: R _t = 4.58 (85.1%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / min .; 210 nm

¹ H NMR (200 MHz, CDCl ₃ ): δ = 1.26 (d, 6H); 3.06 (quin., 1H); 5.29 (s, 1H); 6.23 (s, 1H); 6.65 (dd, 1H); 6.9 (d, 1H); 6.95 (d. 1H); 7.2 (d, 1H); 7.8 (broad s, 1H); 7.97 (s, 2H); 8.27 (broad s, 1H).

Example 19

DL-amino- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis-trifluoromethyl-phenyl} acetic acid

1.0 g (2.06 mmol) of hydantoin from Example 18 are heated to 100 ° C. overnight with 0.493 g (20.6 mmol) of lithium hydroxide in 15 ml of water. The reaction solution is cooled to 0 ° C. and directly reacted further with di-tert-butyl dicarbonate (Example 20).
R _f : 0.39 (methylene chloride: methanol = 8: 2)

Example 20

DL-tert-butoxycarbonylamino- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis-trifluoro methylphenyl} acetic acid

The reaction solution from Example 19 (about 2.06 mmol = 100%) is mixed with 50 ml of dioxane and at 0 ° C. with 0.899 g (4.12 mmol) of di-tert-butyl dicarbonate dissolved in 5 ml of dioxane dropwise implemented. The reaction solution is then allowed to come to room temperature and stirred for 2 hours at room temperature. After the dioxane has been distilled off, the reaction solution is acidified at 0 ° C. with 1 N hydrochloric acid to pH 2 and extracted twice with ethyl acetate. The combined ethyl acetate phases are washed with sodium chloride solution, dried, filtered and concentrated. The crude product (1.234 g) is chromatographed on silica gel 60 using methylene chloride / methanol (9: 1) in the isocratic mode.
Yield: 0.271 g (23.5%)
A second fraction of 0.531 g (HPLC content: 64.0%) is obtained.
MS (LC-MS): 561 ([M + H] ⁺ , 100%)
HPLC: R _t = 0.503 (91.4%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / min .; 210 nm

¹ H NMR (200 MHz, d ₆ -DMSO): δ = 1.18 (d, 6H); 1.38 (s, 9H); 2.93 (m, 1H); 3.33 (broad s, 1H); 4.99 (d, 1H); 6.59 (d, 1H); 6.7 (s, 1H); 7.08 (d, 1H); 7.25 (d, 1H); 8.1 (s, 2H); 10.75 (s, 1H).

Example 21

DL-amino- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis-trifluoromethyl-phenyl} -acetic acid acetate salt

0.526 g (0.945 mmol) of tert-butoxycarbonyl-protected amino acid from Example 20 are dissolved in 7 ml of dichloromethane, cooled to 0 ° C. and 7 ml of trifluoroacetic acid are added dropwise under argon. The solution is then stirred for 45 minutes at room temperature, then concentrated to an oil, the oily residue is stirred with ether and ether is distilled off.
Yield: 0.526 g (as trifluoroacetate salt)

The residue is dissolved in 20% acetic acid (20 ml) with the addition of 10 ml of methanol and passed through a column filled with 80 ml of Amberlite IR-67 (acetate form; Fluka). The mixture is then washed with a water / methanol mixture (1: 1), the eluate is freed from methanol in vacuo and lyophilized.
Yield: 120 mg (27.8%)
MS (EI): 460 ([M] ⁺ , 14%)
HPLC: R _t = 4.29 (79.8%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / min .; 210 nm

Example 22

5- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis-trifluoromethyl-benzylidene} -thiazolidine-2,4-dione

A mixture of 0.52 g (1.25 mmol) aldehyde derivative from Example V, 0.21 g (1.63 mmol) 2,4-thiazolidine-2,4-dione, 0.2 g (1.63 mmol) Benzoic acid and 0.14 g (1.63 mmol) of piperidine in 47.5 ml of toluene are boiled under reflux overnight in the presence of molecular sieve 4 Å powder. The reaction solution is then cooled to room temperature, diluted with 47.5 ml of toluene, suction filtered from the molecular sieve and washed with ethyl acetate. The organic filtrate is washed twice with ammonium chloride solution, dried, filtered and concentrated in vacuo. Chromatography on silica gel 60 using toluene / ethyl acetate (10: 1) in the isocratic mode gives the thiazolidinedione derivative.
Yield: 50 mg (4.9%)
MS (ESI): 515 ([M + H] ⁺ , 100%)
PLC: R _t = 3.72 (63.2%)
0.3 g 30% HCl per 1 l H ₂ O
Symmetry column C 18 (150 × 2.1 mm)
Flow: 0.9 ml / min .; 210 nm

Example 23

6- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis-trifluoromethylphenyl} - [1,3] - thiazinane-2,4-dione

The thiazine derivative is produced as a further product in the preparation of the benzylidene-2,4-thiazolidinedione derivative (Example 22).
Yield: 0.123 g (14.7%)
MS (LC): 517 ([M + H] ⁺ , 100%)
HPLC: R _t = 3.26 (77.3%)
0.3 g 30% HCl per 1 l H ₂ O
Symmetry column C18 (150 × 2.1 mm)
Flow: 0.9 ml / min .; 210 nm

Example 24

3- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis-trifluoromethyl-benzylidene} dihydro furan-2-an

0.36 g (0.87 mmol) of aldehyde derivative from Example V are dissolved in 10 ml of toluene and 0.36 g (1.04 mmol) of butyrolactonylidene-triphenylphosphorane are carried in in portions. After 3 days of stirring at room temperature, the reaction mixture is filtered, the filtrate is concentrated to half the volume and chromatographed on silica gel 60 using toluene / ethyl acetate (9: 1).
Yield: 0.334 g (72.5%)
MS (DCI): 501 ([M + NH ₄ ] ⁺ , 100%)
R _f : 0.87 (toluene: ethyl acetate = 9: 1)

¹ H NMR (200 MHz, CDCl ₃ ): δ = 1.27 (d, 6H); 3.05 (quin, 1H); 3.31 (sext, 2H); 4.55 (t. 2H); 6.71 (dd, 1H); 6.88 (d. 1H); 6.96 (d. 1H); 7.2 (d, 1H); 7.62 (t, 1H); 7. 84 (broad s, 1H); 8.03 (s, 2H).

Example 25

3- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis-trifluoromethyl-benzyl} dihydrofuran-2-one

0.2 g (0.38 mmol) of benzylidene compound from Example 24 are dissolved in 100 ml of methanol and hydrogenated with hydrogen in the presence of palladium on activated carbon for 18 hours. The catalyst is suctioned off through kieselguhr and the filtrate is concentrated in vacuo. The crude product is purified by chromatography on silica gel 60 in isocratic gradient mode with toluene / ethyl acetate (10: 1).
Yield: 94 mg (48.7%)
MS (ESI): 486 ([M + H] ⁺ , 100%)
R _f : 0.35 (toluene: ethyl acetate = 9: 1)

¹ H NMR (300 MHz, CDCl ₃ ): δ = 1.28 (d, 6H); 2.04 (m, 1H); 2.37 (m, 1H); 2.91 (m. 2H); 3.05 (quin, 1H); 3.4 (fourth, 1H); 4.23 (m, 1H); 4.39 (sext, 1H); 6.69 (dd, 1H); 6.85 (d. 1H); 6.94 (d. 1H); 7.2 (d, 1H); 7.77 (s, 2H); 7.8 (s, 1H).

Example 26

5- {4 - [(3-Isopropyl-1H-indol-5-yl) oxy) -3,5-bis-trifluoromethyl-phenyl} -3-oxo-pent-4-ene carboxylic acid, ethyl ester

Analogous to the procedure of Example 24, 0.35 g (0.84 mmol) of aldehyde derivative from Example V with 0.36 g (0.93 mmol) of ethyl 4- (triphenylphosphoranylidene) acetoacetate in 10 ml of toluene are at room temperature for 2 days and then reacted for 18 hours at 75 ° C and 6 hours at 120 ° C. The crude product is purified by column chromatography on silica gel 60 using toluene.
Yield: 0.24 g (47.3%)
MS (ESI): 528 ([M + H] ⁺ , 100%)
HPLC: R _t = 6.00 (27.3%) and R _t = 5.35 (51.2%); E / Z-mixture
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / min .; 210 nm

Example 27

5- {4 - [(3-Isopropyl-1H-indol-5-yl) oxy] -3,5-bis-trifluoromethylphenyl} -3-oxopentane carboxylic acid ethyl ester

Analogously to the procedure of Example 25, 0.2 g (0.38 mmol) of 3-oxopentene-4-carboxylic acid derivative from Example 26 are hydrogenated overnight in methanol with palladium on activated carbon under a hydrogen atmosphere. The crude product is chromatographed on silica gel with toluene / ethyl acetate (10: 1) in the isocratic mode.
Yield: 89 mg (38.6%)
MS (ESI): 530 ([M + H] ⁺ , 100%)
R _f : 0.37 (toluene: ethyl acetate = 9: 1)

¹ H NMR (200 MHz, CDCl ₃ ): δ = 1.28 (d and t, 9H); 3.03 (m, 5H); 3.49 (s, 2H); 4.2 (fourth, 2H); 6.7 (dd, 1H); 6.87 (d. 1H); 6.95 (d. 1H); 7.21 (d, 1H); 7.73 (s, 2H); 7.8 (s, 1H).

Example 28

5- {4 - [(3-Isopropyl-1H-indol-5-yl) oxy) -3,5-bis-trifluoromethylphenyl} pentane carboxylic acid ethyl ester

The pentanecarboxylic acid derivative is formed as a by-product in the catalytic hydrogenation of the 3-oxopentecarboxylic acid derivative in Example 27.
Yield: 15 mg (6.2%)
MS (ESI): 516 ([M + H] ⁺ , 100%)
R _f : 0.4 (toluene: ethyl acetate = 9: 1)

¹ H NMR (200 MHz, CDCl ₃ ): δ = 1.28 (d and t, 9H); 1.73 (quin, 3H); 2.39 (m, 2H); 2.78 (m. 2H); 3.04 (sext, 2H); 4.15 (fourth, 2H); 6.7 (dd, 1H); 6.86 (d, 1H); 6.93 (d, 1H); 7.21 (d, 1H); 7.71 (s, 2H); 7.8 (broad s, 1H).

Example 29

4- (3-cyclohexylmethyl-1H-indol-5-yloxy) -3,5-bis-trifluoromethyl-phenylacetic acid

The preparation is carried out in analogy to the procedure of Example 17 from 0.3 g (0.62 mmol) of phenylacetonitrile derivative from Example XXIII by dissolving the nitrile in 10 ml of dioxane and adding 4 ml of conc. Treated sulfuric acid and 4 ml of water at 100 ° C for 4 hours. The crude product is chromatographed on silica gel 60 using toluene / ethyl acetate (1: 1) in the isocratic mode.
Yield: 65 mg (17.5%)
MS (ESI): 500 ([M + H] ⁺ , 100%)
HPLC: = 5.23 (82.6%)
0.5% HClO ₄ / acetonitrile
Kromasil column C18 (60 × 2 mm)
Flow: 0.75 ml / min .; 210 nm
R _f : 0.29 (toluene: ethyl acetate = 1: 1)

¹ H NMR (200 MHz, CDCl ₃ ): δ = 0.92 (m, 2H); 1.17 (m, 4H); 1.5 (m, 1H); 1.65 (m, 4H); 2.49 (d, 2H); 3.82 (s, 2H); 6.68 (dd, 1H); 6.84 (d, 1H); 6.93 (d, 1H); 7.2 (d, 1H); 7.85 (d and s, 3H).

The following can be produced in an analogous manner:

Example 30

{4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenoxy} acetic acid

Example 31

{4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenoxy} acetic acid

Example 32

{4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -3,5-dimethylphenoxy} acetic acid

Example 33

{4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -3,5-dimethylphenoxy} acetic acid

Example 34

{4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -3,5-dimethylphenoxy} acetic acid

Example 35

{3,5-dimethyl-4 - [(3-propyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 36

{4 - [(3-butyl-1H-indol-5-yl) oxy] -3,5-dimethylphenoxy} acetic acid

Example 37

{3,5-dimethyl-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 38

{4 - [(3-hexyl-1H-indol-5-yl) oxy] -3,5-dimethylphenoxy} acetic acid

Example 39

{4 - [(3-isobutyl-1H-indol-5-yl) oxy] -3,5-dimethylphenoxy} acetic acid  

Example 40

{4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3,5-dimethylphenoxy} acetic acid

Example 41

(4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenoxy) acetic acid

Example 42

(4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenoxy) acetic acid

Example 43

(4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenoxy) acetic acid

Example 44

(4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenoxy) acetic acid

Example 45

{3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 46

{3,5-dichloro-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 47

{3,5-dichloro-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 48

{3,5-dichloro-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 49

{3,5-dichloro-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] phenoxy} acetic acid  

Example 50

{3,5-dichloro-4 - [(3-propyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 51

{4 - [(3-butyl-1H-indol-5-yl) oxy] -3,5-dichlorophenoxy} acetic acid

Example 52

{3,5-dichloro-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 53

{3,5-dichloro-4 - [(3-hexyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 54

{3,5-dichloro-4 - [(3-isobutyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 55

{4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3,5-dichlorophenoxy} acetic acid

Example 56

(3,5-dichloro-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 57

(3,5-dichloro-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 58

(3,5-dichloro-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 59

(3,5-dichloro-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid  

Example 60

{3,5-dibromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 61

{3,5-dibromo-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 62

{3,5-dibromo-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 63

{3,5-dibromo-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 64

{3,5-dibromo-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] phenoxy} acetic acid

Example 65

{3,5-dibromo-4 - [(3-propyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 66

{3,5-dibromo-4 - [(3-butyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 67

{3,5-dibromo-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 68

{3,5-dibromo-4 - [(3-hexyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 69

{3,5-dibromo-4 - [(3-isobutyl-1H-indol-5-yl) oxy] phenoxy} acetic acid  

Example 70

{3,5-dibromo-4 - [(3-sec-butyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 71

(3,5-dibromo-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 72

(3,5-dibromo-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 73

(3,5-dibromo-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 74

(3,5-dibromo-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 75

[4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenoxy] acetic acid

Example 76

[4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenoxy] acetic acid

Example 77

[4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenoxy] acetic acid

Example 78

[4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenoxy] acetic acid

Example 79

[4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -3,5-bis (trifluoromethyl) phenoxy] acetic acid  

Example 80

[4 - [(3-propyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenoxy] acetic acid

Example 81

[4 - [(3-butyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenoxy] acetic acid

Example 82

[4 - [(3-pentyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenoxy] acetic acid

Example 83

[4 - [(3-hexyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenoxy] acetic acid

Example 84

[4 - [(3-isobutyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenoxy] acetic acid

Example 85

[4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenoxy] acetic acid

Example 86

[4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenoxy] - acetic acid

Example 87

[4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenoxy] - acetic acid

Example 88

[4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenoxy] - acetic acid  

Example 89

[4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenoxy] - acetic acid

Example 90

[4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenoxy] acetic acid

Example 91

[4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenoxy] - acetic acid

Example 92

[4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenoxy] acetic acid

Example 93

[4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenoxy] - acetic acid

Example 94

[4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenoxy] - acetic acid

Example 95

[3-Methyl-4 - [(3-propyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 96

[4 - [(3-butyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenoxy] acetic acid

Example 97

[3-Methyl-4 - [(3-pentyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid  

Example 98

[4 - [(3-hexyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenoxy] acetic acid

Example 99

[4 - [(3-isobutyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenoxy] acetic acid

Example 100

[4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenoxy] acetic acid

Example 101

[4 - {(3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -3-methyl-5- (trifluoromethyl) phen oxy] acetic acid

Example 102

[4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -3-methyl- (trifluoromethyl) phen oxy] acetic acid

Example 103

[4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl) oxy} -3-methyl-5- (trifluoromethyl) phen oxy] acetic acid

Example 104

[4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -3-methyl-5- (trifluoromethyl) - phenoxy] acetic acid

Example 105

{3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy) -5-methylphenoxy} acetic acid

Example 106

{3-bromo-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid  

Example 107

{3-bromo-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 108

{3-bromo-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 109

{3-bromo-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 110

{3-bromo-5-methyl-4 - [(3-propyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 111

{3-bromo-4 - [(3-butyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 112

{3-bromo-5-methyl-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 113

{3-bromo-4 - [(3-hexyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 114

{3-bromo-4 - [(3-isobutyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 115

{3-bromo-4 - ((3-sec-butyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 116

(3-bromo-4 - {(3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -5-methylphenoxy) acetic acid  

Example 117

(3-bromo-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -5-methylphenoxy) acetate acid

Example 118

(3-bromo-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -5-methylphenoxy) acetic acid

Example 119

(3-bromo-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -5-methylphenoxy) acetate acid

Example 120

{3-Chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 121

{3-Chloro-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 122

{3-Chloro-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 123

{3-Chloro-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 124

{3-Chloro-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 125

{3-Chloro-5-methyl-4 - [(3-propyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 126

{4 - [(3-butyl-1H-indol-5-yl) oxy] -3-chloro-5-methylphenoxy} acetic acid  

Example 127

{3-Chloro-5-methyl-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 128

{3-Chloro-4 - [(3-hexyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 129

{3-Chloro-4 - [(3-isobutyl-1H-indol-5-yl) oxy] -5-methylphenoxy} acetic acid

Example 130

{4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3-chloro-5-methylphenoxy} acetic acid

Example 131

(3-chloro-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -5-methylphenoxy) acetic acid

Example 132

(3-chloro-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -5-methylphenoxy) acetate acid

Example 133

(3-chloro-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -5-methylphenoxy) acetic acid

Example 134

(3-chloro-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -5-methylphenoxy) acetate acid

Example 135

{3-bromo-5-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenoxy} acetic acid  

Example 136

{3-bromo-5-chloro-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 137

{3-bromo-5-chloro-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 138

{3-bromo-5-chloro-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 139

{3-bromo-5-chloro-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] phenoxy} acetic acid

Example 140

{3-bromo-5-chloro-4 - [(3-propyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 141

{3-bromo-4 - [(3-butyl-1H-indol-5-yl) oxy] -5-chlorophenoxy} acetic acid

Example 142

{3-bromo-5-chloro-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 143

{3-bromo-5-chloro-4 - [(3-hexyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 144

{3-bromo-5-chloro-4 - [(3-isobutyl-1H-indol-5-yl) oxy] phenoxy} acetic acid

Example 145

{3-bromo-4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -5-chlorophenoxy} acetic acid  

Example 146

(3-Bromo-5-chloro-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 147

(3-Bromo-5-chloro-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 148

(3-Bromo-5-chloro-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 149

(3-Bromo-5-chloro-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 150

[3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 151

3-chloro-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 152

[3-chloro-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 153

[3-chloro-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 154

[3-chloro-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 155

[3-chloro-4 - [(3-propyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid  

Example 156

[4 - [(3-butyl-1H-indol-5-yl) oxy] -3-chloro-5- (trifluoromethyl) phenoxy] acetic acid

Example 157

[3-chloro-4 - [(3-pentyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 158

[3-chloro-4 - [(3-hexyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 159

[3-chloro-4 - [(3-isobutyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 160

[4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3-chloro-5- (trifluoromethyl) phenoxy] acetic acid

Example 161

[3-chloro-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) -phen oxy] acetic acid

Example 162

[3-chloro-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenoxy] - acetic acid

Example 163

[3-chloro-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenoxy] - acetic acid

Example 164

[3-chloro-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenoxy] - acetic acid  

Example 165

[3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 166

[3-bromo-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 167

[3-bromo-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 168

[3-bromo-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 169

[3-bromo-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 170

[3-bromo-4 - [(3-propyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 171

[3-bromo-4 - [(3-butyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 172

[3-bromo-4 - [(3-pentyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 173

[3-bromo-4 - [(3-hexyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 174

[3-bromo-4 - [(3-isobutyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid  

Example 175

[3-bromo-4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenoxy] acetic acid

Example 176

[3-bromo-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenoxy] - acetic acid

Example 177

[3-bromo-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenoxy] - acetic acid

Example 178

[3-bromo-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenoxy] - acetic acid

Example 179

[3-bromo-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenoxy] - acetic acid

Example 180

({4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} sulfanyl) acetic acid

Example 181

({3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} sulfanyl) acetic acid

Example 182

({3,5-dibromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} sulfanyl) acetic acid

Example 183

{[4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] sulfanyl} - acetic acid  

Example 184

{[4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] sulfanyl} - acetic acid

Example 185

({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} sulfanyl) acetic acid

Example 186

({3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} sulfanyl) acetic acid

Example 187

({3-bromo-5-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} sulfanyl) acetic acid

Example 188

{[3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] sulfanyl) - acetic acid

Example 189

{[3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] sulfanyl} - acetic acid

Example 190

N- [3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] glycine

Example 191

N- [3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] glycine

Example 192

N- {3-bromo-5-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} glycine  

Example 193

N- {3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} glycine

Example 194

N- {3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} glycine

Example 195

N- [4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] glycine

Example 196

N- [4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] glycine

Example 197

N- {3,5-dibromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} glycine

Example 198

N- {3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} glycine

Example 199

N- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} glycine

Example 200

3 - {[3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] amino} -3- oxopropanoate

Example 201

3 - {[3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] amino} -3- oxopropanoate  

Example 202

3 - ({3-bromo-5-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} amino) -3-oxo propionic acid

Example 203

3 - ({3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxopro propionic acid

Example 204

3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -3-oxo propionic acid

Example 205

3 - {[4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] amino} - 3-oxopropionic acid

Example 206

3 - {[4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] amino} -3- oxopropanoate

Example 207

3 - ({3,5-dibromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} amino) -3-oxopropion acid

Example 208

3 - ({3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} amino) -3-oxopropion acid

Example 209

3 - ({4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} amino) -3-oxopropion acid  

Example 210

3 - {[3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] amino} -2- oxopropanoate

Example 211

3 - {[3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] amino} - 2-oxopropanoate

Example 212

3 - ({3-bromo-5-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} amino) -2-oxopro propionic acid

Example 213

3 - ({3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -2-oxo propionic acid

Example 214

3 - ({3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} amino) -2-oxo propionic acid

Example 215

3 - {[4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] amino} - 2-oxopropanoate

Example 216

3 - {[4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] amino} -2- oxopropanoate  

Example 217

3 - ({3,5-dibromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} amino) -2-oxopropion acid

Example 218

3 - ({3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} amino) -2-oxopropion acid

Example 219

3 - ({4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} amino) -2-oxopropion acid

Example 220

3- [3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] propion acid

Example 221

3- [3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] propion acid

Example 222

3- {3-bromo-5-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} propionic acid

Example 223

3- {3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} -propionic acid

Example 224

3- {3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} propiansäure  

Example 225

3- [4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] -propionic acid

Example 226

3- [4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] propionic acid

Example 227

3- {3,5-dibromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} propionic acid

Example 228

3- {3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} propionic acid

Example 229

3- {4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} -propionic acid

Example 230

[3-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 231

[3-chloro-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 232

[3-chloro-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 233

[3-chloro-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 234

[3-chloro-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid  

Example 235

[3-chloro-4 - [(3-propyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 236

[4 - [(3-butyl-1H-indol-5-yl) oxy] -3-chloro-5- (trifluoromethyl) phenyl] acetic acid

Example 237

[3-chloro-4 - [(3-pentyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 238

[3-chloro-4 - [(3-hexyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 239

[3-chloro-4 - [(3-isobutyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 240

[4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3-chloro-5- (trifluoromethyl) phenyl] acetic acid

Example 241

[3-chloro-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 242

[3-chloro-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 243

[3-chloro-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid  

Example 244

[3-chloro-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 245

[4 - [(3-benzyl-1H-indol-5-yl) oxy] -3-chloro-5- (trifluoromethyl) phenyl] acetic acid

Example 246

[3-chloro-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 247

[3-chloro-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] vinegar acid

Example 248

[3-chloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5- (trifluoromethyl) - phenyl] acetic acid

Example 249

[3-chloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5- (trifluoromethyl) - phenyl] acetic acid

Example 250

[3-chloro-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 251

[3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid  

Example 252

[3-bromo-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 253

[3-bromo-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 254

[3-bromo-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 255

[3-bromo-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 256

[3-bromo-4 - [(3-propyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 257

[3-bromo-4 - [(3-butyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 258

[3-bromo-4 - [(3-pentyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 259

[3-bromo-4 - [(3-hexyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 260

[3-bromo-4 - [(3-isobutyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 261

[3-bromo-4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid  

Example 262

[3-bromo-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 263

[3-bromo-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 264

[3-bromo-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 265

[3-bromo-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 266

[4 - [(3-benzyl-1H-indol-5-yl) oxy] -3-bromo-5- (trifluoromethyl) phenyl] acetic acid

Example 267

[3-bromo-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 268

[3-bromo-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 269

[3-bromo-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5- (trifluoromethyl) - phenyl] acetic acid  

Example 270

[3-bromo-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5- (trifluoromethyl) - phenyl] acetic acid

Example 271

[3-bromo-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 272

{3-bromo-5-chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 273

{3-bromo-5-chloro-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 274

{3-bromo-5-chloro-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 275

{3-bromo-5-chloro-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 276

{3-bromo-5-chloro-4 - [(3-cyclohexy1-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 277

{3-bromo-5-chloro-4 - [(3-propyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 278

{3-bromo-4 - [(3-butyl-1H-indol-5-yl) oxy] -5-chlorophenyl} acetic acid

Example 279

{3-bromo-5-chloro-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenyl} acetic acid  

Example 280

{3-bromo-5-chloro-4 - [(3-hexyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 281

{3-bromo-5-chloro-4 - [(3-isobutyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 282

{3-bromo-4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -5-chlorophenyl} acetic acid

Example 283

(3-Bromo-5-chloro-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl) oxy} phenyl) acetic acid

Example 284

(3-Bromo-5-chloro-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 285

(3-Bromo-5-chloro-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 286

(3-Bromo-5-chloro-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl) oxy} phenyl) acetic acid

Example 287

{4 - [(3-benzyl-1H-indol-5-yl) oxy] -3-bromo-5-chlorophenyl} acetic acid

Example 288

(3-bromo-5-chloro-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 289

(3-Bromo-5-chloro-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} phenyl) acetic acid  

Example 290

[3-bromo-5-chloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] - acetic acid

Example 291

[3-bromo-5-chloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] - acetic acid

Example 292

(3-Bromo-5-chloro-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 293

{3-bromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 294

{3-bromo-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 295

{3-bromo-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 296

{3-bromo-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 297

{3-bromo-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -5-methylphenyl} acetic acid

Example 298

{3-bromo-5-methyl-4 - [(3-propyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 299

{3-bromo-4 - [(3-butyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid  

Example 300

{3-bromo-5-methyl-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 301

{3-bromo-4 - [(3-hexyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 302

{3-bromo-4 - [(3-isobutyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 303

{3-bromo-4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 304

(3-bromo-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid

Example 305

(3-bromo-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid

Example 306

(3-bromo-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid

Example 307

(3-bromo-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid

Example 308

{4 - [(3-benzyl-1H-indol-5-yl) oxy] -3-bromo-5-methylphenyl} acetic acid

Example 309

(3-bromo-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid  

Example 310

(3-bromo-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid

Example 311

[3-bromo-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5-methylphenyl] - acetic acid

Example 312

[3-bromo-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5-methylphenyl] acetate acid

Example 313

(3-Bromo-5-methyl-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 314

{3-Chloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 315

{3-Chloro-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 316

{3-Chloro-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 317

{3-Chloro-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 318

{3-Chloro-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -5-methylphenyl} acetic acid

Example 319

{3-Chloro-5-methyl-4 - [(3-propyl-1H-indol-5-yl) oxy] phenyl} acetic acid  

Example 320

{4 - [(3-butyl-1H-indol-5-yl) oxy] -3-chloro-5-methylphenyl} acetic acid

Example 321

{3-Chloro-5-methyl-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 322

{3-Chloro-4 - [(3-hexyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 323

{3-Chloro-4 - [(3-isobutyl-1H-indol-5-yl) oxy] -5-methylphenyl} acetic acid

Example 324

{4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3-chloro-5-methylphenyl} acetic acid

Example 325

(3-chloro-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid

Example 326

(3-chloro-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid

Example 327

(3-chloro-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid

Example 328

(3-chloro-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid

Example 329

{4 - [(3-benzyl-1H-indol-5-yl) oxy] -3-chloro-5-methylphenyl} acetic acid  

Example 330

(3-chloro-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid

Example 331

(3-chloro-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -5-methylphenyl) acetic acid

Example 332

[3-chloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5-methylphenyl] - acetic acid

Example 333

[3-chloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5-methylphenyl] - acetic acid

Example 334

(3-chloro-5-methyl-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 335

[4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] acetic acid

Example 336

[4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] acetic acid

Example 337

[4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] acetic acid

Example 338

[4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] acetic acid

Example 339

[4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] acetic acid  

Example 340

[3-Methyl-4 - [(3-propyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 341

[4 - [(3-butyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] acetic acid

Example 342

[3-Methyl-4 - [(3-pentyl-1H-indol-5-yl) oxy] -5- (trifluoromethyl) phenyl] acetic acid

Example 343

[4 - [(3-hexyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] acetic acid

Example 344

[4 - [(3-isobutyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] acetic acid

Example 345

[4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] acetic acid

Example 346

[4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -3-methyl-5- (trifluoromethyl) phenyl] - acetic acid

Example 347

[4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -3-methyl-5- (trifluoromethyl) phenyl] - acetic acid

Example 348

[4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -3-methyl-5- (trifluoromethyl) phenyl] - acetic acid  

Example 349

[4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -3-methyl-5- (trifluoromethyl) phenyl] - acetic acid

Example 350

[4 - [(3-benzyl-1H-indol-5-yl) oxy] -3-methyl-5- (trifluoromethyl) phenyl] acetic acid

Example 351

[4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -3-methyl-5- (trifluoromethyl) phenyl] - acetic acid

Example 352

[4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -3-methyl-5- (trifluoromethyl) phenyl] - acetic acid

Example 353

[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3-methyl-5- (trifluoromethyl) - phenyl] acetic acid

Example 354

[4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3-methyl-5- (trifluoromethyl) - phenyl] acetic acid

Example 355

[3-Methyl-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} -5- (trifluoromethyl) phenyl] - acetic acid

Example 356

[4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid  

Example 357

[4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 358

[4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 359

[4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 360

[4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 361

[4 - [(3-propyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 362

[4 - [(3-butyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 363

[4 - [(3-pentyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 364

[4 - [(3-hexyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 365

[4 - [(3-isobutyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 366

[4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid  

Example 367

[4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] - acetic acid

Example 368

[4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy) -3,5-bis (trifluoromethyl) phenyl] - acetic acid

Example 369

[4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] vinegar acid

Example 370

[4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] - acetic acid

Example 371

[4 - [(3-benzyl-1H-indol-5-yl) oxy] -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 372

[4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 373

[4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -3,5-bis (tri fluoromethyl) phenyl] acetic acid

Example 374

[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phenyl] - acetic acid  

Example 375

[4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phenyl] - acetic acid

Example 376

[4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 377

{3,5-dibromo-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 378

{3,5-dibromo-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 379

{3,5-dibromo-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 380

{3,5-dibromo-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 381

{3,5-dibromo-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] phenyl} acetic acid

Example 382

{3,5-dibromo-4 - [(3-propyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 383

{3,5-dibromo-4 - [(3-butyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 384

{3,5-dibromo-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenyl} acetic acid  

Example 385

{3,5-dibromo-4 - [(3-hexyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 386

{3,5-dibromo-4 - [(3-isobutyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 387

{3,5-dibromo-4 - [(3-sec-butyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 388

(3,5-dibromo-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 389

(3,5-dibromo-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 390

(3,5-dibromo-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 391

(3,5-dibromo-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 392

{4 - [(3-benzyl-1H-indol-5-yl) oxy] -3,5-dibromophenyl} -acetic acid

Example 393

(3,5-dibromo-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 394

(3,5-dibromo-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} phenyl) acetic acid  

Example 395

[3,5-dibromo-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetic acid

Example 396

[3,5-dibromo-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetic acid

Example 397

(3,5-dibromo-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 398

{3,5-dichloro-4 - [(3-isopropyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 399

{3,5-dichloro-4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 400

{3,5-dichloro-4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 401

{3,5-dichloro-4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 402

{3,5-dichloro-4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] phenyl} acetic acid

Example 403

{3,5-dichloro-4 - [(3-propyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 404

{4 - [(3-butyl-1H-indol-5-yl) oxy] -3,5-dichlorophenyl} acetic acid  

Example 405

{3,5-dichloro-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 406

{3,5-dichloro-4 - [(3-hexyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 407

{3,5-dichloro-4 - [(3-isobutyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 408

{4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3,5-dichlorophenyl} acetic acid

Example 409

(3,5-dichloro-4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 410

(3,5-dichloro-4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 411

(3,5-dichloro-4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 412

(3,5-dichloro-4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 413

{4 - [(3-benzyl-1H-indol-5-yl) oxy] -3,5-dichlorophenyl} acetic acid

Example 414

(3,5-dichloro-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} phenyl) acetic acid  

Example 415

(3,5-dichloro-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 416

[3,5-dichloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetic acid

Example 417

[3,5-dichloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetic acid

Example 418

(3,5-dichloro-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 419

{4 - [(3-isopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} acetic acid

Example 420

{4 - [(3-cyclopropyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} acetic acid

Example 421

{4 - [(3-cyclobutyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} acetic acid

Example 422

{4 - [(3-cyclopentyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} acetic acid

Example 423

{4 - [(3-cyclohexyl-1H-indole-5-yl) oxy] -3,5-dimethylphenyl} acetic acid

Example 424

{3,5-dimethyl-4 - [(3-propyl-1H-indol-5-yl) oxy] phenyl} acetic acid  

Example 425

{4 - [(3-butyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} acetic acid

Example 426

{3,5-dimethyl-4 - [(3-pentyl-1H-indol-5-yl) oxy] phenyl} acetic acid

Example 427

{4 - [(3-hexyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} acetic acid

Example 428

{4 - [(3-isobutyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} acetic acid

Example 429

{4 - [(3-sec-butyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} acetic acid

Example 430

(4 - {[3- (cyclohexylmethyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenyl) acetic acid

Example 431

(4 - {[3- (cyclopentylmethyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenyl) acetic acid

Example 432

(4 - {[3- (cyclobutylmethyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenyl) acetic acid

Example 433

(4 - {[3- (cyclopropylmethyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenyl) acetic acid

Example 434

{4 - [(3-benzyl-1H-indol-5-yl) oxy] -3,5-dimethylphenyl} acetic acid  

Example 435

(4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenyl) acetic acid

Example 436

(4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenyl) acetic acid

Example 437

[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] acetic acid

Example 438

[4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] acetic acid

Example 439

(3,5-dimethyl-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 440

(3,5-dimethyl-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 441

(3,5-dichloro-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 442

(3,5-dibromo-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 443

[4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} -3,5-is (trifluoromethyl) phenoxy] acetic acid

Example 444

(3,5-dimethyl-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid  

Example 445

3,5-dichloro-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 446

(3,5-dibromo-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 447

[4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] acetic acid

Example 448

3,5-dimethyl-O- [3- (phenylsulfonyl) -1H-indol-5-yl] -D-tyrosine

Example 449

3,5-dichloro-O- [3- (phenylsulfonyl) -1H-indol-5-yl] -D-tyrosine

Example 450

3,5-dibromo-O- [3- (phenylsulfonyl) -1H-indol-5-yl] -D-tyrosine

Example 451

O- [3- (phenylsulfonyl) -1H-indol-5-yl] -3,5-bis (trifluoromethyl) -D-tyrosine

Example 452

3,5-dimethyl-O- [3- (phenylsulfonyl) -1H-indol-5-yl] -L-tyrosine

Example 453

3,5-dichloro-O- [3- (phenylsulfonyl) -1H-indol-5-yl] -L-tyrosine

Example 454

3,5-dibromo-O- [3- (phenylsulfonyl) -1H-indol-5-yl] -L-tyrosine

Example 455

O- [3- (phenylsulfonyl) -1H-indol-5-yl] -3,5-bis (trifluoromethyl) -L-tyrosine  

Example 456

(3,5-dimethyl-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) methanesulfonic acid

Example 457

(3,5-dichloro-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) methanesulfonic acid

Example 458

(3,5-dibromo-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) methanesulfonic acid

Example 459

[4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] methane sulfonic acid

Example 460

[(3,5-dimethyl-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) sulfanyl] acetate acid

Example 461

[(3,5-dichloro-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) sulfanyl] acetic acid

Example 462

[(3,5-dibromo-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) sulfanyl] acetic acid

Example 463

{[4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] sul fanyl} acetic acid

Example 464

(2R) -amino (3,5-dimethyl-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) ethane acid  

Example 465

(2R) -amino (3,5-dichloro-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) ethane acid

Example 466

(2R) -amino (3,5-dibromo-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) ethane acid

Example 467

(2R) -amino [4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluorniethyl) - phenyl] ethanoic acid

Example 468

(2S) -amino (3,5-dimethyl-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) - ethanoate

Example 469

(2S) -amino (3,5-dichloro-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) ethane acid

Example 470

(2S) -amino (3,5-dibromo-4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} phenyl) - ethanoate

Example 471

(2S) -amino [4 - {[3- (phenylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) - phenyl] ethanoic acid

Example 472

[4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenoxy] acetate acid  

Example 473

[3,5-dichloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenoxy] acetic acid

Example 474

[3,5-dibromo-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenoxy] acetic acid

Example 475

[4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phen oxy] acetic acid

Example 476

[4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] acetic acid

Example 477

[3,5-dichloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetic acid

Example 478

[3,5-dibromo-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetic acid

Example 479

[4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phenyl] - acetic acid

Example 480

O- {3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} -3,5-dimethyl-D-tyrosine

Example 481

3,5-dichloro-O- {3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} -D-tyrosine  

Example 482

3,5-dibromo-O- {3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} -D-tyrosine

Example 483

O- {3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} -3,5-bis (trifluoromethyl) -D-tyrosine

Example 484

O- {3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} -3,5-dimethyl-L-tyrosine

Example 485

3,5-dichloro-O- {3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} -L-tyrosine

Example 486

3,5-dibromo-O- {3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} -L-tyrosine

Example 487

O- {3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} -3,5-bis (trifluoromethyl) -L-tyrosine

Example 488

[4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] methane sulfonic acid

Example 489

[3,5-dichloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] methane sulfonic acid

Example 490

[3,5-dibromo-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] methane sulfonic acid  

Example 491

[4 - ({3 - [(4-fFuorphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phenyl] - methanesulfonic

Example 492

{[4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] sul fanyl} acetic acid

Example 493

{[3,5-dichloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] sulfanyl} - acetic acid

Example 494

{[3,5-dibromo-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] sulfanyl} - acetic acid

Example 495

{[4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) - phenyl] sulfanyl} acetic acid

Example 496

(2R) -amino [4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethyl phenyl] -ethanoic

Example 497

(2R) -amino [3,5-dichloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] - ethanoate

Example 498

(2R) -amino [3,5-dibromo-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] - ethanoate  

Example 499

(2R) -amino [4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoro methyl) phenyl] ethanoic acid

Example 500

(2S) -amino [4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethyl phenyl] -ethanoic

Example 501

(2S) -amino [3,5-dichloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] - ethanoate

Example 502

(2S) -amino [3,5-dibromo-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] - ethanoate

Example 503

(2S) -amino [4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoro methyl) phenyl] ethanoic acid

Example 504

[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenoxy] acetate acid

Example 505

[3,5-dichloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenoxy] acetic acid

Example 506

[3,5-dibromo-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenoxy] acetic acid  

Example 507

[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phen oxy] acetic acid

Example 508

[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] acetic acid

Example 509

[3,5-dichloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetic acid

Example 510

[3,5-dibromo-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetic acid

Example 511

[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phenyl] - acetic acid

Example 512

O- {3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} -3,5-dimethyl-D-tyrosine

Example 513

3,5-dichloro-O- {3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} -D-tyrosine

Example 514

3,5-dibromo-O- {3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} -D-tyrosine

Example 515

O- {3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} -3,5-bis (trifluoromethyl) -D-tyrosine

Example 516

O- {3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} -3,5-dimethyl-L-tyrosine  

Example 517

3,5-dichloro-O- {3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} -L-tyrosine

Example 518

3,5-dibromo-O- {3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} -L-tyrosine

Example 519

O- {3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} -3,5-bis (trifluoromethyl) -L-tyrosine

Example 520

[4 - ({3 - ((4-Clorphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] methane sulfonic acid

Example 521

[3,5-dichloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] methane sulfonic acid

Example 522

[3,5-dibromo-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] methane sulfonic acid

Example 523

[4 - ({3 - ((4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phenyl] - methanesulfonic

Example 524

{[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] sul fanyl} acetic acid  

Example 525

{[3,5-dichloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] sulfanyl} - acetic acid

Example 526

{[3,5-dibromo-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] sulfanyl} - acetic acid

Example 527

{[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phe nyl] sulfanyl} acetic acid

Example 528

(2R) -amino [4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethyl phenyl] ethanoic acid

Example 529

(2R) -amino [3,5-dichloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid

Example 530

(2R) -amino [3,5-dibromo-4 - ({3 - [(4-chlorophenyl) sulfanyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid

Example 531

(2R) -amino [4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoro methyl) phenyl] ethanoic acid

Example 532

(2S) -amino [4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethyl phenyl] ethanoic acid  

Example 533

(2S) -amino [3,5-dichloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid

Example 534

(2S) -amino [3,5-dibromo-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid

Example 535

(2S) -amino [4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoro methyl) phenyl] ethanoic acid

Example 536

[3,5-dimethyl-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenoxy] - acetic acid

Example 537

[3,5-dichloro-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenoxy] acetate acid

Example 538

[3,5-dibromo-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenoxy] acetate acid

Example 539

[4 - ({3 - [(4-methylphenyl) 19902 00070 552 001000280000000200012000285911979100040 0002010130830 00004 19783sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) - phenoxy] acetic acid  

Example 540

[3,5-dimethyl-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetate acid

Example 541

[3,5-dichloro-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetic acid

Example 542

[3,5-dibromo-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetic acid

Example 543

[4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phe nyl] acetic acid

Example 544

3,5-dimethyl-O- {3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} -D-tyrosine

Example 545

3,5-dichloro-O- {3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} -D-tyrosine

Example 546

3,5-dibromo-O- {3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} -D-tyrosine

Example 547

O- {3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} -3,5-bis (trifluoromethyl) -D-tyrosine

Example 548

3,5-dimethyl-O- {3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} -L-tyrosine

Example 549

3,5-dichloro-O- {3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} -L-tyrosine  

Example 550

3,5-dibromo-O- {3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} -L-tyrosine

Example 551

O- {3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} -3,5-bis (trifluoromethyl) -L-tyrosine

Example 552

[3,5-dimethyl-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] methane sulfonic acid

Example 553

[3,5-dichloro-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] methane sulfonic acid

Example 554

[3,5-dibromo-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] methane sulfonic acid

Example 555

[4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phe nyl] methanesulfonic

Example 556

{[3,5-dimethyl-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] - sulfanyl} acetic acid

Example 557

{[3,5-dichloro-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] sul fanyl} acetic acid  

Example 558

{[3,5-dibromo-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] sul fanyl) acetic acid

Example 559

{[4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) - phenyl] sulfanyl} acetic acid

Example 560

(2R) -amino [3,5-dimethyl-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid

Example 561

(2R) -amino [3,5-dichloro-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid

Example 562

(2R) -amino [3,5-dibromo-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid

Example 563

(2R) -amino [4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoro methyl) phenyl] ethanoic acid

Example 564

(2S) -amino [3,5-dimethyl-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid  

Example 565

(2S) -amino [3,5-dichloro-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) phe nyl] -ethanoic

Example 566

(2S) -amino [3,5-dibromo-4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid

Example 567

(2S) -amino [4 - ({3 - [(4-methylphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoro methyl) phenyl] ethanoic acid

Example 568

(3,5-dimethyl-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 569

(3,5-dichloro-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 570

(3,5-dibromo-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenoxy) acetic acid

Example 571

[4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenoxy] - acetic acid

Example 572

(3,5-dimethyl-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 573

(3,5-dichloro-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid  

Example 574

(3,5-dibromo-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) acetic acid

Example 575

[4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] - acetic acid

Example 576

3,5-dimethyl-O- [3- (4-pyridinylsulfonyl) -1H-indol-5-yl] -D-tyrosine

Example 577

3,5-dichloro-O- [3- (4-pyridinylsulfonyl) -1H-indol-5-yl] -D-tyrosine

Example 578

3,5-Dibromo-O- [3- (4-pyridinylsulfonyl) -1H-indol-5-yl] -D-tyrosine

Example 579

O- [3- (4-pyridinylsulfonyl) -1H-indol-5-yl] -3,5-bis (trifluoromethyl) -D-tyrosine

Example 580

3,5-dimethyl-O- [3- (4-pyridinylsulfonyl) -1H-indol-5-yl] -L-tyrosine

Example 581

3,5-dichloro-O- [3- (4-pyridinylsulfonyl) -1H-indol-5-yl] -L-tyrosine

Example 582

3,5-Dibromo-O- [3- (4-pyridinylsulfonyl) -1H-indol-5-yl] -L-tyrosine

Example 583

O- [3- (4-pyridinylsulfonyl) -1H-indol-5-yl] -3,5-bis (trifluoromethyl) -L-tyrosine  

Example 584

(3,5-dimethyl-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) rnethan sulfonic acid

Example 585

(3,5-dichloro-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) methanesulfonic acid

Example 586

(3,5-dibromo-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) methane sulfonic acid

Example 587

[4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] - methanesulfonic

Example 588

[(3,5-dimethyl-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) sulfanyl] - acetic acid

Example 589

[(3,5-dichloro-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) sulfanyl] - acetic acid

Example 590

[(3,5-dibromo-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) sulfanyl] - acetic acid  

Example 591

{[4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] - sulfanyl} acetic acid

Example 592

(2R) -amino (3,5-dimethyl-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) - ethanoate

Example 593

(2R) -amino (3,5-dichloro-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) - ethanoate

Example 594

(2R) -amino (3,5-dibromo-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) - ethanoate

Example 595

(2R) -amino [4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) - phenyl] ethanoic acid

Example 596

(2S) -amino (3,5-dimethyl-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) - ethanoate

Example 597

(2S) -amino (3,5-dichloro-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) - ethanoate

Example 598

(2S) -amino (3,5-dibromo-4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} phenyl) - ethanoate  

Example 599

(2S) -Amino [4 - {[3- (4-pyridinylsulfonyl) -1H-indol-5-yl] oxy} -3,5-bis (tri fluoromethyl) - phenyl] ethanoic acid

Example 600

[4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenoxy] - acetic acid

Example 601

[3,5-dichloro-4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenoxy] - acetic acid

Example 602

[3,5-dibromo-4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenoxy] - acetic acid

Example 603

[4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) - phenoxy] acetic acid

Example 604

[4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] - acetic acid

Example 605

[3,5-dichloro-4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] acetate acid  

Example 606

[3,5-dibromo-4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] - acetic acid

Example 607

[4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) - phenyl] acetic acid

Example 608

O- {3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} -3,5-dimethyl-D-tyrosine

Example 609

3,5-dichloro-O- {3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} -D-tyrosine

Example 610

3,5-dibromo-O- {3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} -D-tyrosine

Example 611

O- {3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} -3,5-bis (trifluoromethyl) -D-tyrosine

Example 612

O- {3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} -3,5-dimethyl-L-tyrosine

Example 613

3,5-dichloro-O- {3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} -L-tyrosine

Example 614

3,5-dibromo-O- {3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} -L-tyrosine

Example 615

O- {3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} -3,5-bis (trifluoromethyl) -L-tyrosine  

Example 616

[4 - ((3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] me than-sulfonic acid

Example 617

[3,5-dichloro-4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] methane sulfonic acid

Example 618

[3,5-dibromo-4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] methane sulfonic acid

Example 619

[4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) - phenyl] methane

Example 620

{[4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] - sulfanyl} acetic acid

Example 621

{[3,5-dichloro-4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] - sulfanyl} acetic acid

Example 622

{[3,5-dibromo-4 - ((3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] - sulfanyl} acetic acid  

Example 623

{[4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) - phenyl] sulfanyl} acetic acid

Example 624

(2R) -amino [4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethyl phenyl] ethanoic acid

Example 625

(2R) -amino [3,5-dichloro-4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid

Example 626

(2R) -amino [3,5-dibromo-4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid

Example 627

(2R) -amino [4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoro methyl) phenyl] ethanoic acid

Example 628

(2S) -amino [4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethyl phenyllethansäure

Example 629

(2S) -amino [3,5-dichloro-4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid

Example 630

(2S) -Amino [3,5-dibromo-4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) - phenyl] ethanoic acid  

Example 631

(2S) -amino [4 - ({3 - [(4-methoxyphenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoro methyl) phenyl] ethanoic acid

Example 632

{3,5-dimethyl-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) oxy] - phenoxy} acetic acid

Example 633

{3,5-dichloro-4 - phen - [({[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl 3) oxy] oxy} acetic acid

Example 634

{3,5-dibromo-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) oxy] -phen oxy} acetic acid

Example 635

{3,5-bis (trifluoromethyl) -4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) - oxy] phenoxy} acetic acid

Example 636

{3,5-dimethyl-4 - [(3 - {(4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) oxy] phenyl} - acetic acid

Example 637

{3,5-dichloro-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) oxy] phenyl} - acetic acid  

Example 638

{3,5-dibromo-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) oxy] phenyl} - acetic acid

Example 639

{3,5-bis (trifluoromethyl) -4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) - oxy] phenyl} acetic acid

Example 640

3,5-dimethyl-O- (3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) -D-tyro sin

Example 641

3,5-dichloro-O- (3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) -D-tyro sin

Example 642

3,5-dibromo-O- (3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) -D-tyrosine

Example 643

3,5-Bis (trifluoromethyl) -O- (3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) -D tyrosine

Example 644

3,5-dimethyl-O- (3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) -L-tyrosine

Example 645

3,5-dichloro-O- (3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) -L-tyrosine

Example 646

3,5-dibromo-O- (3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) -L-tyro sin  

Example 647

3,5-Bis (trifluoromethyl) -O- (3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) -L tyrosine

Example 648

{3,5-dimethyl-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) oxy] phenyl} - methanesulfonic

Example 649

{3,5-dichloro-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) oxy] phenyl} - methanesulfonic

Example 650

{3,5-dibromo-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) oxy] phenyl} - methanesulfonic

Example 651

{3,5-bis (trifluoromethyl) -4 - [(3 - {[4- (trifluoromethyl) phenyl) sulfonyl} -1H-indol-5-yl) - oxy] phenyl} methane sulfonic acid

Example 652

({3,5-dimethyl-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) oxy] -Phe nyl} sulfanyl) acetic acid

Example 653

({3,5-dichloro-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) oxy] -Phe nyl} sulfanyl) acetic acid

Example 654

({3,5-dibromo-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) oxy] - phenyl} sulfanyl) acetic acid  

Example 655

({3,5-bis (trifluoromethyl) -4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1 H - [- indol-5-yl) - oxy] phenyl} sulfanyl) acetic acid

Example 656

(2R) -amino {3,5-dimethyl-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indole-5- yl) oxy] phenyl} acetic acid

Example 657

(2R) -amino {3,5-dichloro-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) - oxy] phenyl} acetic acid

Example 658

(2R) -amino {3,5-dibromo-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) - oxy] phenyl} acetic acid

Example 659

(2R) -amino {3,5-bis (trifluoromethyl) -4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H- indol-5-yl) oxy] phenyl} acetic acid

Example 660

(2S) -Amino {3,5-dimethyl-4 - [(3 - {[4- (tri fluoromethyl) phenyl] sulfonyl} -1H-indole-5- yl) oxy] phenyl} acetic acid

Example 661

(2S) -amino {3,5-dichloro-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indol-5-yl) - oxy] phenyl} acetic acid  

Example 662

(2S) -amino {3,5-dibromo-4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H-indole-5- yl) oxy] phenyl} acetic acid

Example 663

(2S) -amino {3,5-bis (trifluoromethyl) -4 - [(3 - {[4- (trifluoromethyl) phenyl] sulfonyl} -1H- indol-5-yl) oxy] phenyl} acetic acid

Example 664

Difluoro (4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenyl) acetic acid

Example 665

(4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenyl) (difluoro) acetic acid

Example 666

[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] (difluoro) - acetic acid

Example 667

Difluoro [4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] - acetic acid

Example 668

Fluoro [4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] acetic acid

Example 669

[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-dimethylphenyl] (fluoro) - acetic acid  

Example 670

(4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenyl) (fluoro) acetic acid

Example 671

Fluoro (4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -3,5-dimethylphenyl) acetic acid

Example 672

(3-chloro-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -5-methylphenyl) (fluoro) acetic acid

Example 673

(3-chloro-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -5-methylphenyl) (fluoro) acetate acid

Example 674

[3-chloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5-methylphenyl] - (Fluoro) acetic acid

Example 675

3-chloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5-methylphenyl] (fluoro) - acetic acid

Example 676

[3-chloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5-methylphenyl] - (Difluoro) acetic acid

Example 677

[3-chloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -5-methylphenyl] - (Difluoro) acetic acid  

Example 678

(3-chloro-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -5-methylphenyl) (difluoro) - acetic acid

Example 679

(3-chloro-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -5-methylphenyl) (difluoro) vinegar acid

Example 680

(3,5-dichloro-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} phenyl) (difluoro) acetic acid

Example 681

(3,5-dichloro-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} phenyl) (difluoro) acetic acid

Example 682

[3,5-dichloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] (difluoro) - acetic acid

Example 683

[3,5-dichloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] (difluoro) - acetic acid

Example 684

[3,5-dichloro-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] (fluoro) - acetic acid

Example 685

[3,5-dichloro-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] (fluoro) - acetic acid  

Example 686

(3,5-dichloro-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} phenyl) (fluoro) acetic acid

Example 687

(3,5-dichloro-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} phenyl) (fluoro) acetic acid

Example 688

(3,5-dibromo-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} phenyl) (fluoro) acetic acid

Example 689

(3,5-dibromo-4 - {[3- (4-chlorbenzy1) -1H-indol-5-yl] oxy} phenyl) (fluoro) acetic acid

Example 1690

[3,5-dibromo-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] (fluoro) - acetic acid

Example 691

[3,5-dibromo-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] (fluoro) - acetic acid

Example 692

[3,5-dibromo-4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] (difluoro) - acetic acid

Example 693

[3,5-dibromo-4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) phenyl] (difluoro) - acetic acid

Example 694

(3,5-dibromo-4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} phenyl) (difluoro) es acetic acid  

Example 695

(3,5-dibromo-4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} phenyl) (difluoro) acetic acid

Example 696

Difluoro [4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] - acetic acid

Example 697

[4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] (difluoro) - acetic acid

Example 698

[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phenyl] - (Difluoro) acetic acid

Example 699

Difluoro [4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) - phenyl] acetic acid

Example 700

Fluoro [4 - ({3 - [(4-fluorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) - phenyl] acetic acid

Example 701

[4 - ({3 - [(4-chlorophenyl) sulfonyl] -1H-indol-5-yl} oxy) -3,5-bis (trifluoromethyl) phenyl] - (Fluoro) acetic acid

Example 702

[4 - {[3- (4-chlorobenzyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] - (fluoro) - acetic acid  

Example 703

Fluoro [4 - {[3- (4-fluorobenzyl) -1H-indol-5-yl] oxy} -3,5-bis (trifluoromethyl) phenyl] - acetic acid

Claims (20)

1. Compounds of the general formula (I)
in which
Z represents O, S, SO, SO ₂ , CH ₂ , CHF, CF ₂ or NR ⁹ , where R ^{9 is} hydrogen or (C ₁ -C ₄ ) alkyl,
R ¹ and R ^{2 are} identical or different and represent hydrogen, halogen, cyano, (C ₁ -C ₆ ) alkyl, CF ₃ , CHF ₂ , CH ₂ F, vinyl or (C ₃ -C ₇ ) cycloalkyl, where at least one of the two substituents is not hydrogen and is in the ortho position to the bridge bond,
R ³ for a group of the formula
A _m -D _n -E _o -G _p -LR ¹⁰
stands in what
A represents O, S, NR ¹¹ or the group - (CR ¹² = CR ¹³ ) -, in which R ^{11 is} hydrogen or (C ₁ -C ₄ ) alkyl, and R ¹² and R ^{13 are} identical or different and Is hydrogen, cyano, (C ₁ -C ₄ ) -alkyl or (C ₁ -C ₄ ) -alkoxy,
D represents a straight-chain (C ₁ -C ₃ ) alkylene group which, one or more times, the same or different, by (C ₁ -C ₄ ) alkyl, hydroxy, (C ₁ -C ₄ ) alkoxy, halogen, Amino, mono- (C ₁ -C ₄ ) -alkylamino, mono- (C ₁ -C ₄ ) -acylamino or (C ₁ -C ₄ ) -alkoxycarbonylamino may be substituted,
E and L independently of one another represent a C (O) or SO ₂ group,
G represents NR ¹⁴ , in which R ^{14 represents} hydrogen or (C ₁ -C ₄ ) -alkyl, or represents a straight-chain (C ₁ -C ₃ ) -alkylene group which is one or more times, identical or different, by (C ₁ -C ₄ ) alkyl, hydroxy, (C ₁ -C ₄ ) alkoxy, halogen, amino, mono- or di- (C ₁ -C ₄ ) alkylamino or mono- (C ₁ -C ₄ ) acylamino can be substituted
m, n, o and p each independently represent the number 0 or 1, with the proviso that
in the event that L stands for a C = O group, the sum (m + n + o + p) is not equal to the number 0,
and
in the event that m and o each represent the number 1, A the remainder NR ¹¹ and E and L each represent a C = O group, the sum (n + p) is not equal to the number 0,
and
R ¹⁰ for OR ¹⁵ , NR ¹⁶ R ¹⁷ , (C ₁ -C ₁₀ ) alkyl, (C ₃ -C ₈ ) cycloalkyl, (C ₂ -C ₆ ) alkenyl, (C ₆ -C ₁₀ ) aryl , (C ₆ -C ₁₀ ) arylmethyl or a saturated, partially unsaturated or aromatic 5- to 10-membered heterocycle with up to four identical or different hetero atoms from the series N, O and / or S, where the aforementioned radicals optionally by one, two or three identical or different substituents selected from the group halogen, hydroxy, oxo, cyano, nitro, amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ - C ₆ ) alkyl, optionally by R. ²⁰ substituted (C ₁ -C ₆ ) alkoxy, (C ₃ -C ₈ ) cycloalkyl, (C ₆ -C ₁₀ ) aryl, which in turn may be substituted by halogen, (C ₁ -C ₄ ) alkyl, (C ₁ -C ₄ ) alkoxy, trifluoromethyl, nitro or cyano, -OC (O) -R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ -NR ²⁵ R ²⁶ , -NH-C (O) -R ²⁷ and -NH-C (O) -OR ^{28 are} substituted, wherein
R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each represents hydrogen, Phenyl, benzyl, (C ₁ -C ₆ ) alkyl or (C ₃ -C ₈ ) cycloalkyl, which in turn are optionally one or more, identical or different, by halogen, hydroxyl, amino, carboxyl, (C ₁ - C ₄ ) -alkoxy, (C ₁ -C ₄ ) -alkoxycarbonyl, (C ₁ -C ₄ ) -alkoxy-carb onylamino, (C ₁ -C ₅ ) -alkanoyloxy, a heterocycle or optionally substituted by halogen or hydroxy-substituted phenyl are,
or the group
-LR ¹⁰ for a group of the formula
stands in what
R ²⁹ denotes hydrogen or (C ₁ -C ₄ ) alkyl,
or
R ³ for a group of the formula
stands in what
Q represents a 5- to 6-membered saturated, partially unsaturated or aromatic heterocycle with up to four identical or different heteroatoms from the series N, O and / or S, which in turn is optionally one to three times, identical or different, by oxo (= O), thioxo (= S), hydroxy, (C ₁ - C ₆ ) alkyl or phenyl,
r represents the number 0, 1 or 2,
and
the ring Het is a 5- to 6-membered saturated or partially unsaturated heterocycle with up to three identical or different heteroatoms from the series N, O and / or S, which may be one to three times, identical or different, by oxo (= O), thioxo (= S), hydroxy, (C ₁ -C ₆ ) alkyl or phenyl,
R ⁴ and R ^{5 are the} same or different and each represents hydrogen, hydroxy, halogen, cyano, nitro, (C ₁ -C ₄ ) alkyl or the rest of the formula NR ³⁰ R ³¹ , where R ³⁰ and R ^{31 are} those for R ¹⁵ have the meaning given and, independently of one another, can be identical or different with this substituent,
R ^{6 represents} hydrogen, halogen or a group of the formula
-M _a -R ³²
stands in what
M represents a carbonyl group, a sulfonyl group or a methylene group,
a represents the number 0 or 1,
and
R ^{32 has} the meaning of R ¹⁰ given above and can be identical or different with this substituent,
R ^{7 represents} hydrogen or an acyl group which can be split off under physiological conditions to form an NH function, preferably represents hydrogen or acetyl,
and
R ^{8 has} the meaning of R ⁶ given above and can be the same or different with this substituent, and their pharmaceutically acceptable salts, solvates, hydrates and hydrates of the salts. 2. Compounds according to claim 1,
in which
Z represents O, S or CH ₂ ,
R ¹ and R ^{2 are the} same or different and are hydrogen, fluorine, chlorine, bromine, (C ₁ -C ₄ ) alkyl, CF ₃ , CHF ₂ , CH ₂ F, vinyl or (C ₃ -C ₅ ) cycloalkyl are, where at least one of the two substituents is not hydrogen and is in the ortho position to the bridge bond, in particular both substituents are not hydrogen and both are in the ortho position,
R ³ for a group of the formula
A _m -D _n -E _o -G _p -LR ¹⁰
stands in what
A represents O, S, NR ¹¹ or the group - (CR ¹² = CR ¹³ ) -, in which R ¹¹ denotes hydrogen or methyl, and R ¹² and R ^{13 are} identical or different and denote hydrogen or methoxy,
D stands for a straight-chain (C ₁ -C ₃ ) alkylene group which is mono- or divalent, identical or different, by (C ₁ -C ₄ ) alkyl, flydroxy, methoxy, ethoxy, fluorine, chlorine, amino, mono- (C ₁ - C ₄₎ alkylamino, or mono- (C ₁ -C ₄₎ acylamino may be substituted,
E represents a C (O) group,
L represents a C (O) or SO ₂ group,
G represents an NH group or a straight-chain (C ₁ -C ₃ ) alkylene group which is mono- or discrete, identical or different, by methyl, ethyl, hydroxy, methoxy, fluorine, chlorine, amino, methylamino or Acetylamino may be substituted
m, n, o and p each independently represent the number 0 or 1, with the proviso that
in the event that L stands for a C = O group, the sum (m + n + o + p) is not equal to the number 0,
and
in the event that m and o each represent the number 1, A represents the radical NR ¹¹ and L represents a C = O group, the sum (n + p) is not equal to the number 0,
and
R ¹⁰ for OR ¹⁵ , NR ¹⁶ R ¹⁷ , (C ₁ -C ₆ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, naphthyl, phenyl, benzyl or for a saturated, partially unsaturated or aromatic 5- to 6- membered heterocycle with up to four identical or different heteroatoms from the series N, O and / or S, the abovementioned radicals optionally being selected from the group halogen, hydroxyl, oxo, cyano, nitro by one, two or three identical or different substituents , Amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ -C ₄ ) alkyl, optionally substituted by R ²⁰ (C ₁ -C ₄ ) alkoxy, (C ₃ -C ₆ ) cycloalkyl, -OC (O) -R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ -NR ²⁵ NR ²⁶ , -NH-C (O) -R ²⁷ and -NH-C (O ) -OR ^{28 are} substituted, wherein
R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each represents hydrogen, Phenyl, benzyl, (C ₁ -C ₆ ) alkyl or (C ₃ -C ₆ ) cycloalkyl, which in turn are optionally one or more, identical or different, by halogen, hydroxyl, amino, carboxyl, (C ₁ - C ₄ ) -alkoxy, (C ₁ -C ₄ ) -alkoxycarbonyl, (C ₁ -C ₄ ) -alkoxy-carb onylamino, (C ₁ -C ₅ ) -alkanoyloxy, a heterocycle or optionally substituted by halogen or hydroxy-substituted phenyl are,
or
R ³ for a group of the formula
stands,
R ⁴ and R ^{5 are the} same or different and each represents hydrogen, halogen or (C ₁ -C ₄ ) alkyl,
R ^{6 represents} hydrogen, halogen or a group of the formula M _a -R ³² , in which
M represents a carbonyl group, a sulfonyl group or a methylene group,
a represents the number 0 or 1,
and
R ^{32 represents} (C ₁ -C ₁₀ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, (C ₂ -C ₄ ) alkenyl, naphthyl, phenyl, benzyl, pyridyl, pyridazinyl or pyridazinonyl, the aforementioned radicals optionally by one, two or three identical or different substituents selected from the group halogen, hydroxy, cyano, nitro, amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ -C ₄ ) alkyl, (C ₁ -C ₄ ) Alkoxy, (C ₃ -C ₇ ) cycloalkyl, phenyl, which in turn is optionally substituted by halogen, (C ₁ -C ₄ ) alkyl, (C ₁ -C ₄ ) alkoxy, trifluoromethyl, nitro or cyano, -O- C (O) -R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ -NR ²⁵ R ²⁶ , -NH- C (O) -R ²⁷ and -NH-C (O) -OR ^{28 are} substituted, wherein
R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each represents hydrogen, phenyl, benzyl, (C ₁ -C ₆ ) -alkyl or (C ₃ -C ₆ ) -cycloalkyl, which in turn are optionally one or more, identical or different, by halogen, hydroxy, amino, carboxyl, (C ₁ -C ₄ ) -alkoxy, (C ₁ -C ₄ ) alkoxycarbonyl, (C ₁ -C ₄ ) alkoxycarbonylamino, (C ₁ - C ₅ ) alkanoyloxy, a heterocycle or phenyl which is optionally substituted by halogen or hydroxy,
R ^{7 represents} hydrogen,
and
R ^{8 has} the meaning of R ⁶ given above and can be identical or different with this substituent,
and their pharmaceutically acceptable salts, solvates, hydrates and hydrates of the salts. 3. Compounds according to claim 1,
in which
Z represents O or CH ₂ ,
R ¹ and R ^{2 are the} same or different and are hydrogen, fluorine, chlorine, bromine, (C ₁ -C ₄ ) alkyl, CF ₃ , CHF ₂ , CH ₂ F, vinyl or (C ₃ -C ₅ ) cycloalkyl are, where at least one of the two substituents is not hydrogen and is in the ortho position to the bridge bond, in particular both substituents are not hydrogen and both are in the ortho position,
R ³ for a group of the formula
A _m -D _n -E _o -G _p -LR ¹⁰
stands in what
A represents O, S or NH,
D represents a straight-chain (C ₁ -C ₃ ) alkylene group which can be substituted one or two times, identically or differently, by methyl, ethyl, hydroxy, methoxy, fluorine, amino or acetylamino,
E represents a C (O) group,
L represents a C (O) or SO ₂ group,
G represents an NH group or a methylene group,
m, n, o and p each independently represent the number 0 or 1, with the proviso that
in the event that L stands for a C = O group, the sum (m + n + o + p) is not equal to the number 0,
and
in the event that m and o each represent the number 1, A represents the remainder NH and L represents a C = O group, the sum (n + p) is not equal to the number 0,
and
R ¹⁰ for OR ¹⁵ , NR ¹⁶ R ¹⁷ , (C ₁ -C ₆ ) alkyl, phenyl, benzyl or for an aromatic 5- to 6-membered heterocycle with up to four identical or different heteroatoms from the series N, O and / or S, where the abovementioned radicals are optionally selected from the group fluorine, chlorine, hydroxyl, oxo, cyano, nitro, amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ -C. ₎ by one, two or three identical or different substituents ₄ ) alkyl, optionally substituted by R ²⁰ (C ₁ -C ₄ ) alkoxy, (C ₃ -C ₆ ) cycloalkyl, -OC (O) -R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ -NR ²⁵ R ²⁶ , -NH-C (O) -R ²⁷ and -NH-C (O) -OR ^{28 are} substituted, wherein
R ¹⁵ , R ¹⁶ , R ¹⁷ , R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each represents hydrogen, Phenyl, benzyl, (C ₁ -C ₆ ) alkyl or (C ₃ -C ₆ ) cycloalkyl, which in turn are optionally one to two times, identical or different, by fluorine, chlorine, hydroxy, amino, carboxyl, (C ₁ -C ₄ ) alkoxy, (C ₁ -C ₄ ) alkoxycarbonyl, (C ₁ -C ₄ ) alkoxy carbonylamino, (C ₁ -C ₅ ) alkanoyloxy, a heterocycle or optionally substituted by fluorine, chlorine or hydroxy Phenyl are substituted,
R ⁴ and R ^{5 are the} same or different and each represents hydrogen, fluorine, chlorine or methyl,
R ^{6 represents} hydrogen, halogen or a group of the formula
-M _a -R ³²
stands in what
M represents a sulfonyl group or a methylene group,
a represents the number 0 or 1,
and
R ^{32 represents} (C ₁ -C ₁₀ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, phenyl, benzyl, pyridyl, pyridazinyl or pyridazinonyl, the above-mentioned radicals optionally being selected by one or two identical or different substituents from the group fluorine, chlorine, bromine, hydroxy, cyano, nitro, amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ -C ₄ ) alkyl, (C ₁ -C ₄ ) alkoxy, (C ₃ -C ₇ ) - Cycloalkyl, -OC (O) -R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ -NR ²⁵ R ²⁶ , -NH-C (O) -R ²⁷ and -NH-C (O) -OR ^{28 are} substituted, wherein
R ¹⁸ , R ¹⁹ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each represents hydrogen, phenyl, benzyl, (C ₁ -C ₆ ) - Are alkyl or (C ₃ -C ₆ ) cycloalkyl, which in turn, if appropriate, one or two times, identically or differently, by fluorine, chlorine, hydroxyl, amino, carboxyl, (C ₁ -C ₄ ) alkoxy, (C ₁ - C ₄ ) -alkoxycarbonyl, (C ₁ -C ₄ ) -alkoxycarbonylamino, (C ₁ -C ₅ ) -alkanoyloxy, a heterocycle or optionally substituted by fluorine, chlorine or hydroxy-substituted phenyl,
R ^{7 represents} hydrogen,
R ^{8 represents} hydrogen, carboxyl, (C ₁ -C ₄ ) alkoxycarbonyl, (C ₁ -C ₆ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, phenyl, benzyl, pyridyl, phenylsulfonyl or benzylsulfonyl, where the the aforementioned radicals optionally selected from the group of fluorine, chlorine, bromine, hydroxy, cyano, nitro, amino, NR ¹⁸ R ¹⁹ , trifluoromethyl, (C ₁ -C ₄ ) alkyl, (C ₁ -C ₄ ) alkoxy, (C ₃ - C ₆ ) cycloalkyl, -OC (O) -R ²¹ , -C (O) -OR ²² , -C (O) -NR ²³ R ²⁴ , -SO ₂ - NR ²⁵ R ²⁶ , -NH-C (O) -R ²⁷ and -NH-C (O) -OR ^{28 are} substituted, wherein
R ¹⁸ , R ¹⁹ , R ²⁰ , R ²¹ , R ²² , R ²³ , R ²⁴ , R ²⁵ , R ²⁶ , R ²⁷ and R ^{28 are the} same or different and each represents hydrogen, phenyl, benzyl, (C ₁ - C ₆ ) -alkyl or (C ₃ -C ₆ ) -cycloalkyl, which in turn are optionally one or more, identical or different, by fluorine, chlorine, hydroxyl, amino, carboxyl, (C ₁ -C ₄ ) -alkoxy, (C ₁ -C ₄ ) alkoxycarbonyl, (C ₁ -C ₄ ) alkoxycarbonyl amino, (C ₁ -C ₅ ) alkanoyloxy, a heterocycle or optionally substituted by fluorine, chlorine or hydroxy-substituted phenyl, and their pharmaceutical compatible salts, solvates, hydrates and hydrates of the salts. 4. Compounds according to claim 1,
in which
Z stands for O,
R ¹ and R ^{2 are the} same or different and are hydrogen, fluorine, chlorine, bromine, (C ₁ -C ₄ ) alkyl, CF ₃ , CHF ₂ , CH ₂ F, vinyl or (C ₃ -C ₅ ) cycloalkyl are, where at least one of the two substituents is not hydrogen and is in the ortho position to the bridge bond, in particular both substituents are not hydrogen and both are in the ortho position,
R ³ for a group of the formula
-A _m -D _n -E _o -G _p -LR ¹⁰
stands in what
A represents O, S or NH,
D represents a methylene or ethylene group which can be substituted one to two times, identically or differently, by methyl, ethyl, fluorine, amino or acetylamino,
E represents a C (O) group,
L represents a C (O) or SO ₂ group,
G represents an NH group or a methylene group,
m, n, o and p each independently represent the number 0 or 1, with the proviso that
in the event that L stands for a C = O group, the sum (m + n + o + p) is not equal to the number 0,
and
in the event that m and o each represent the number 1, A represents the remainder NH and L represents a C = O group, the sum (n + p) is not equal to the number 0,
and
R ^{10 represents} OR ¹⁵ , NR ¹⁶ R ¹⁷ or (C ₁ -C ₄ ) alkyl, where R ¹⁵ , R ¹⁶ and R ^{17 are the} same or different and each represents hydrogen, phenyl, benzyl, (C ₁ -C ₆ ) -alkyl or (C ₃ -C ₆ ) -cycloalkyl, which in turn are optionally one or two times, identical or different, by fluorine, chlorine, hydroxy, amino, carboxyl, (C ₁ -C ₄ ) -alkoxy, ( C ₁ -C ₄ ) alkoxycarbonyl, (C ₁ -C ₄ ) alkoxycarbonylamino, (C ₁ -C ₅ ) alkanoyl oxy, a heterocycle or phenyl,
R ⁴ and R ^{5 are the} same or different and each represents hydrogen, fluorine, chlorine or methyl,
R ^{6 represents} hydrogen, halogen, (C ₁ -C ₁₀ ) alkyl, (C ₃ -C ₇ cycloalkyl, (C ₃ - C ₇ ) cycloalkylmethyl, phenyl, benzyl, pyridazinonylmethyl, phenyl sulfonyl or pyridylsulfonyl, where the aforementioned aromatic radicals are optionally substituted by one or two identical or different substituents selected from the group consisting of fluorine, chlorine, cyano, nitro, trifluoromethyl, methyl, methoxy, carboxyl or methoxycarbonyl,
R ^{7 represents} hydrogen,
R ^{8 represents} hydrogen, (C ₁ -C ₆ ) alkyl, (C ₃ -C ₇ ) cycloalkyl, phenyl, benzyl, phenylsulfonyl or benzylsulfonyl, the aforementioned aromatic radicals optionally being selected by one or two identical or different substituents the group fluorine, chlorine, cyano, trifluoromethyl, methyl or methoxy are substituted, and their pharmaceutically acceptable salts, solvates, hydrates and hydrates of the salts. 5. Compounds according to claim 1, in which
Z represents CH ₂ or in particular oxygen,
R ¹ and R ^{2 are} identical or different and represent methyl, ethyl, propyl, isopropyl, chlorine, bromine, CF ₃ , vinyl or cyclopropyl, both substituents being in the ortho position to the bridge bond,
R ⁴ and R ⁵ independently of one another represent methyl, fluorine or chlorine or in particular hydrogen,
and
R ^{7 represents} hydrogen. 6. A compound according to any one of claims 1 to 5, in which Z is oxygen stands. 7. A compound according to any one of claims 1 to 6, in which R ^{3 represents} a group of the formula
which is in the para position to the bridge bond and in which R ¹⁰ stands for hydroxy or the radical -C (O) -R ^{10 has} the meanings given for R ¹⁰ for a group which, in the sense of a prodrug to the carboxylic acid -C ( O) - OH or its salts can be broken down. 8. Compounds according to any one of claims 1 to 7, in which R ⁴ , R ⁵ and R ^{7 are} hydrogen. 9. Compounds according to any one of claims 1 to 8, in which R ¹ and R ^{2 are} both arranged in the ortho position to Z and are bromine, trifluoromethyl, ethyl, cyclopropyl and in particular methyl or chlorine. 10. Compounds of formula (Ia)
in which
R ^{3 represents} a group of the formula -CH ₂ -C (O) -OH, -CHF-C (O) -OH or -CF ₂ -C (O) -OH,
and
R ⁶ for straight-chain or branched (C ₁ -C ₈ ) alkyl
stands, and their pharmaceutically acceptable salts, solvates, hydrates and hydrates of the salts. 11. Medicaments containing at least one compound of the general Formula (I) or (Ia) as defined in claims 1 to 10. 12. Medicaments containing at least one compound of the general Formula (I) or (Ia) as defined in claims 1 to 10, and at least at least one excipient and / or carrier commonly used in pharmacology. 13. A process for the manufacture of medicaments, characterized in that at least one compound of the general formula (I) or (Ia) as in claims 1 to 10 defined with auxiliaries and carriers in one suitable application form transferred. 14. Use of the compounds of general formula (I) as in the Claims 1 to 10 defined in the prevention and control of Diseases. 15. Use of compounds of general formula (I) as in the Claims 1 to 10 defined in the treatment and / or prophylaxis of Arteriosclerosis and hypercholesterolemia. 16. Use of compounds of general formula (I) according to mind least one of claims 1 to 8 for the manufacture of medicaments for the Prophylaxis and / or treatment of disease forms with natural Thyroid hormone can be treated. 17. Use of compounds of the general formula (I) according to mind at least one of claims 14 to 16 in combination with other drugs convey.   18. Disease prevention and control procedures, thereby characterized that patients with a connection as in An sayings 1 to 10 defined, treated. 19. A process for the preparation of compounds of the general formula (I) as defined in claim 1, characterized in that reactive indole derivatives of the general formula (II) with reactive phenyl derivatives of the general formula (III)
wherein the substituents R ¹ , R ² , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ^{8 have} the meanings given in claim 1, and
R ^{3 'has} the meaning given for R ³ or for NO ₂ , NH ₂ , NH-PG, OH, O-PG, SH, S-PG, or for an aldehyde, cyano, carboxyl or (C ₁ - C ₄ ) alkoxy-carbonyl group,
where PG stands for a protective group,
X and Y each represent groups of opposite reactivity, z. B.
X can be an electrophilic radical that reacts with a nucleophilic Y substituent and vice versa,
Z 'has the meaning given for Z or represents CH-OH or C = O,
if appropriate in the presence of inert solvents and catalysts and if appropriate with isolation of the intermediates of the general formula (IV) or directly to give compounds of the formula (I). 20. Compounds of the formula (Ib)
in which
R ¹ and R ^{2 are} identical or different and represent bromine, trifluoromethyl, ethyl, cyclopropyl and in particular methyl or chlorine,
R ^{3 represents} a group of the formula -NH-C (O) -CH ₂ -C (O) -R ¹⁰ , wherein
R ¹⁰ stands for hydroxy or the radical -C (O) -R ^{10 has} the meanings given above of R ¹⁰ for a group which can be degraded as a prodrug to the carboxylic acid -C (O) -OH or its salts,
and
R ⁶ for straight-chain or branched (C ₁ -C ₈ ) alkyl
stands.