CA2403806A1 - Indoles for treating diseases that can be treated using thyroid hormones - Google Patents

Abstract

The invention relates to novel indole derivatives, to methods for the production thereof and to their use in medicaments.

Description

Le A 34 254-Foreign Countries Lin/vos/NT
,, Indoles The invention relates to novel indole derivatives, to processes for their preparation and to their use in medicaments.
EP-A-580 550 describes oxamic acid derivatives having cholesterol-lowering properties in animals. A pharmacological property which is particularly emphasized is the reduction of plasma cholesterol, in particular of LDL cholesterol.
Cholesterol-lowering effects are also described in EP-A-188 351 for certain diphenyl ethers having thyroid-hormone-like effects, the chemical structure of which differs clearly from the compounds according to the invention.
Indoles which are attached in the 5-position via a bridge to a substituted phenyl ring are known (WO 94!14770; EP-A-674 619 A1 or WO 94/26737). No thyroid-hormone-like properties have been described for these 5-substituted indoles.
WO 99/50268 discloses substituted indolealkanecarboxylic acids which are suitable for treating chronic complications caused by diabetes mellitus.
WO 95/20588 discloses indole derivatives acting as 5-HT1 agonists.
WO 98/11895 discloses the use of 5-HT1 agonists for treatment of migraine;
suitable active compounds mentioned include indole derivatives. WO 98/06402 describes, for the same structures, the use for the treatment of colds or rhinitis.
EP-A-639 573 discloses benzo-fused 5-membered heterocycles and their use in medicaments and diagnostics. The compounds that are disclosed are inhibitors of the cellular sodium/proton antiporter.
_ Le A 34 254-Foreign Countries US-A-5 468 899 relates to bicyclic aryl compounds having selective properties, for use as LTB4-antagonists.
EP-A-377 450 discloses substituted indole, benzofuran and benzothiophene derivatives acting as S-lipoxygenase inhibitors.
JP-A 07145 147 discloses testosterone 5-alpha-reductase inhibitors derived from benzoic acid which can be used for treating prostate cancer and certain disorders associated with hair loss.
GB-A-2 253 848 describes phenyl indole ethers which are di-ortho-substituted in the phenyl moiety and which have herbicidal action and can be used as crop protection agents. Thyromimetic actions of these ortho-substituted indoles have hitherto not been disclosed.
It is an object of the invention to provide novel compounds having improved, in particular pharmaceutic, actions.
It has now been found that compounds of the general formula (I) H_ Rs R~
/ ~ z r I I (I) ~ N Ra RZ Ra R
in which Z represents O, S, CH2, CHF or CF2, R1 and R2 are identical or different and represent hydrogen, halogen, (Ci-C6)-alkyl, CF3, CHF2, CH2F, vinyl or (C3-C~)-cycloalkyl, where at least one of the two substituents is not hydrogen and is located in the position ortho to the bridge bond, Le A 34 254-Foreign Countries R3 represents a head group with an optionally derivatized carboxyl radical, preferably of the formula A-(CH2)n-(CO)m R8, in which A represents CH2, O, S, CO or represents NR9, in which R9 represents hydrogen, (Ct-C6)-alkyl or (C3-Cg)-cycloalkyl, or represents the group I O -(CH2)n-(CO),t,-O-(C 1-C4)-alkyl, n represents a number from 0 to 3, m represents 1 or 2, Rg represents hydrogen, hydroxyl, OR1~, NRt tRl2, (C1-Cg)_alkyl, (C3-Cg)-cycloalkyl, (C6-Clp)-aryl, or represents a saturated, unsaturated or aromatic 5- to IO-membered heterocycle having up to four identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned radicals are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, vitro, amino, CF3, (C t-C6)-alkyl, optionally R23-substituted (C1-C6)-alkoxy, (C3-Cg)-cycloalkyl, -OCO-R13, -CO-O-Rt4, -CO-NR15R16, _NHCOR1~ and -NHCOOR1~, where Rio, Ri l, R12, R13~ Rt4, R15, R16, R1'7 and R23 are identical or different and each represents hydrogen, phenyl, benzyl, (C1-C6)-alkyl, (CI-C6)-alkoxy or (C3-Cg)-cycloalkyl which for their part are optionally mono-or polysubstituted by halogen, hydroxyl, amino, (C1-C4)-alkoxy, -CO-O(C t-C4)-alkyl, -NH-CO-O(C i-C4)-alkyl, -O-CO-(C ~-C4)-alkyl, by a heterocycle or by optionally halogen- or hydroxyl-substituted phenyl, Le A 34 254-Foreign Countries R4 and RS are identical or different and each represents hydrogen, hydroxyl, halogen, cyano, vitro, (C1-C4)-alkyl, or the radical of the formula NRt8Rt9, where R18 and R19 have the meanings given for R1~ and can be identical to or different from this substituent, R6 represents halogen or has the meaning given for Rg and is identical to or different from this substituent or represents the radical R2° R2i R2z in which RZ~ and R21 together with the carbon atom to which they are attached form a carbonyl group, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C1-C6)-alkyl, (C~-C6)-alkoxy or the radical -NR15R16 and R2' has the meaning of Rg and is identical to or different from this substituent, R~ represents hydrogen or represents an acyl group which can be cleaved off under physiological conditions forming an NH function, preferably represents hydrogen or acetyl, and their salts, preferably the compounds which are mono-, in particular disubstituted in the phenyl moiety, and preferably substituted in the 2-, 4- and 6-position, and which have a substituent in the 3-position of the indole ring Ix A 34 254-Foreign Countries have pharmacological action and can be used as a medicament or for preparing medicament formulations.
The following heterocycles are preferred in the definition of R8 and R6:
A 5- to 8-membered saturated, partially unsaturated or aromatic, optionally benzo-fused heterocycle having up to 4 heteroatoms from the group consisting of S, N
and O, i.e. a heterocycle which may contain one or more double bonds and which is attached via a ring carbon atom or a ring nitrogen atom. Examples which may be mentioned are: tetrahydrofur-2-yl, tetrahydrofur-3-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrrolin-1-yl, piperidin-1-yl, piperidin-3-yl, 1,2-dihydropyridin-1-yl, 1,4-dihydropyridin-1-yl, piperazin-1-yl, morpholin-1-yl, azepin-1-yl, 1,4-diazepin-1-yl, furanyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, triazolyl, tetrazolyl, pyridyi, pyrimidyl, pyrazinyl, pyrimidinonyl, pyridazinonyl.
From among this list, preference is given to: pyridyl, pyrimidyl, pyridazinyl, pyrimidinonyl, pyridazinonyl and thiophenyl. -Derivatized carboxyl radicals in the definition of the substituent R3 are preferably groups which can be degraded in the sense of a prodrug to give the carboxylic acid or a salt thereof, such as, by way of example and by way of preference, halides, anhydrides, esters and/or amides.
In the context of the invention, alkyl represents a straight-chain or branched alkyl radical having preferably 1 to 15, 1 to 12, 1 to 10, 1 to 8, 1 to 6, 1 to 4 or 1 to 3 carbon atoms. Preference is given to a straight-chain or branched alkyl radical having 1 to 3 carbon atoms. By way of example and way of preference, the following radicals may be mentioned: methyl, ethyl, n-propyl, isopropyl, n-, i-, s- or t-butyl, n-pentyl and n-hexyl.

Ix A 34 254-Foreign Countries In the context of the invention, ar~I represents an aromatic radical having preferably 6 to 10 carbon atoms. Preferred aryl radicals are phenyl and naphthyl.
In the context of the invention, cycloalkyl represents a cycloalkyl group having preferably 3 to 8, 3 to 7 or 3 to 6 carbon atoms. By way of example and by way of preference, the following radicals may be mentioned: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.
In the content of the invention, alkoxy preferably represents a straight-chain or branched alkoxy radical having 1 to 6 carbon atoms. Preference is given to a straight-chain or branched alkoxy radical having 1 to 3 carbon atoms. By way of example and by way of preference, the following radicals may be mentioned: methoxy, ethoxy, n-propoxy, isopropoxy, t-butoxy, n-pentoxy and n-hexoxy.
In the context of the invention, haloa_ en includes fluorine, chlorine, bromine and iodine. Preference is given to fluorine, chlorine or bromine.
Depending on the substitution pattern, the compounds according to the invention can exist in stereoisomeric forms which are either like image and mirror image (enantiomers) or which are not like image and mirror image {diastereomers).
The invention relates both to the enantiomers or diastereomers and to their respective mixtures. The racemates, like the diastereomers, can be separated in a known manner into the stereoisomerically uniform components.
Furthermore, certain compounds can be present in tautomeric forms. This is known to the person skilled in the art, and such compounds are likewise embraced by the scope of the invention The compounds according to the invention can also be present as salts. In the context of the invention, preference is given to physiologically acceptable salts.

Le A 34 254-Forei~,n Countries Physiologically acceptable salts can be salts of the compounds according to the invention with inorganic or organic acids. Preference is given to salts with inorganic acids such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid or sulphuric acid, or to salts with organic carboxylic or sulphonic acids such as, for example, acetic acid, propionic acid, malefic acid, fumaric acid, malic acid, citric acid, tartaric acid, lactic acid, benzoic acid, or methanesulphonic acid, ethanesulphonic acid, benzenesulphonic acid, toluenesulphonic acid or naphthalenedisulphonic acid.
Physiologically acceptable salts can also be salts of the compounds according to the invention with bases such as, for example, metal or ammonium salts. Preferred examples are alkali metal salts (for example sodium salts or potassium salts), alkaline earth metal salts (for example magnesium salts or calcium salts), and also ammonium salts derived from ammonia or organic amines, such as, for example, ethylamine, di-or triethylamine, ethyldiisopropylamine, monoethanolamine, di- or triethanolamine, dicyclohexylamine, dimethylaminoethanol, dibenzylamine, N-methylmorpholine, dihydroabietylamine, I-ephenamine, methylpiperidine, arginine, lysine, ethylenediamine or 2-phenylethylamine.
The compounds according to the invention can also be present in the form of their solvates, in particular in the form of their hydrates.
Preference is given to compounds of the general formula (I) , in which Z represents O, CH2 or CF2, Ri and R2 are identical or different and represent hydrogen, fluorine, chlorine, bromine, (Ct-C4)-alkyl, CF3, CHF2, CHZF, vinyl or (C3-C6)-cycloalkyl, where at least one of the two substituents is not hydrogen and is located in the Le A 34 254-Fore Countries _g_ position ortho to the bridge bond, and where in particular both substituents are not hydrogen and both are located in the ortho-position, R3 represents a head group with optionally derivatized carboxyl radical, preferably a group of the formula A-(CH2)n-(CO)m R8, located in the position para to the bridge bond, in which A represents CH2, n represents 0 or 1, m represents 1 or 2, R8 represents hydrogen, hydroxyl, OR1~, NR1 1R12, (Ci-C6)_alkyl, (C3-Cg)-cycloalkyl, (C6-Cep)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to four identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C3-Cg)-cycloalkyl, O-CO-R13, -CO-O-R14, -CO-NR15R16 and -NHCOOR1~, where R10, R11~ R12~ R13~ R14, R15~ R16 and R1~ are identical or different and each represents hydrogen, benzyl, (C1-C4)-alkyl or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (C1-C4)-alkoxy, Le A 34 254-Foreign Countries R4 and RS are identical or different and each represents hydrogen, halogen or (C1-C4)-alkyl, R6 has the meaning given for R8 and is identical to or different from this above substituent or represents the radical R2° R2i 'R22 in which R2~ and R2t together represent oxygen, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (Ci-C4)-alkyl, (Ct-Cq,)-alkoxy or the radical -NR15R16 and R22 has the meaning of R8 and is identical to or different from this substituent, R~ represents hydrogen, and their salts.
Preference is given to compounds of the general formula (I), in which Z represents O, CH2 or CFZ, R1 and R' are identical or different and represent hydrogen, fluorine, chlorine, bromine, (Ct-C4)-alkyl, CF3, CHF2, CH2F, vinyl or (C3-C6)-cycloalkyl, where at least one of the two substituents is not hydrogen and is located in the Le A 34 254-Foreign Countries position ortho to the bridge bond, and where in particular both substituents are not hydrogen and both are located in the ortho-position, R3 represents a head group with optionally derivatized carboxyl radical, preferably represents a group of the formula A-(CH2)~-(CO)m R8, located in the position para to the bridge bond, in which A represents O, n represents 0 or 1, m represents 1 or 2, R$ represents hydrogen, hydroxyl, ORt~, NRt1R12, (C1_C6)_alkyl, (C3-Cg)-cycloalkyl, (C6-Ctp)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to four identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (Ct-C4)-alkyl, (Ci-C4)-alkoxy, (C3-Cg)-cycloaIkyl, O-CO-R13, -CO-O-Rt4, -CO-NRi5R16 and -NHCOORi~, where RiO, R11~ R12, R13~ R14~ R15~ R16 and R1~ are identical or different and each represents hydrogen, benzyl, (Ci-CQ)-alkyl or (C3-C6)-cycIoalkyI
which for their part are optionally substituted by amino or (C1-C4)-alkoxy, Le A 34 254-Foreign Countries R4 and RS are identical or different and each represents hydrogen, halogen or (CI-C4)-alkyl, R6 has the meaning given for R8 and is identical to or different from this above substituent or represents the radical R2° R2~
~ R22 in which R2~ and RZi together represent oxygen, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C1-C4)-alkyl, (C1-C4)-alkoxy or the radical -NR15R16 and R22 has the meaning of R8 and is identical to or different from this substituent, R~ represents hydrogen, and their salts.
Preference is given to compounds of the general formula (I), in which Z represents O, CH2 or CF2, R1 and R2 are identical or different and represent hydrogen, fluorine, chlorine, bromine, (C1-CQ)-alkyl, CF3, CHF2> CH2F, vinyl or (C3-C6)-cycloalkyl, where at least one of the two substituents is not hydrogen and is located in the Le A 34 254-Foreign Countries position ortho to the bridge bond, and where in particular both substituents are not hydrogen and both are located in the ortho-position, R3 represents a head group with optionally derivatized carboxyl radical, preferably represents a group of the formula A-(CH~)n-(CO)m R8, located in the position para to the bridge bond, in which A represents NR9, in which R9 represents hydrogen, (Ci-CQ)-alkyl or (C3-C~)-cycloalkyl, n represents 0 or 1, m represents 1 or 2, R8 represents hydrogen, hydroxyl, OR1~, NRjlRi2, (C1-C~)-alkyl, (C3-Cg)-cycloalkyl, (C6-Clp)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to four identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, vitro, amino, CF3, (C~-C4)-alkyl, (C1-C4)-alkoxy, (C3-Cg)-cycloalkyl, O-CO-R13, -CO-O-Rj4, -CO-NRt5R16 and -NHCOOR1~, where Rio, R11~ Rl2t R13~ R14, R15~ R16 and R17 are identical or different and each represents hydrogen, benzyl, (C1-C4)-alkyl or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (C~-C4)-alkoxy, Le A 34 254-Foreign Countries R4 and RS are identical or different and each represents hydrogen, halogen or (C1-C4)-alkyl, R6 has the meaning given for Rg and is identical to or different from this substituent or represents the radical R2~

in which R2~ and R21 together represent oxygen, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C 1-C4)-alkyl, (C1-C4)-alkoxy or the radical -NRt5Rt6 and R22 has the meaning of R8 and is identical to or different from this substituent, R~ represents hydrogen, and their salts.
Preference is given to compounds of the general formula (I), in which Z represents O, CHZ or CF2, Ri and R2 are identical or different and represent hydrogen, fluorine, chlorine, bromine, (Ct-C4)-alkyl, CF3, CHF2, CH2F, vinyl or (C3-C6)-cycloalkyl, where at least one of the two substituents is not hydrogen and is located in the Le A 34 254-Fore Countries position ortho to the bridge bond, where in particular both substituents are not hydrogen and both are located in the ortho position, R3 represents a head group with optionally derivatized carboxyl radical, preferably of the formula A-(CH2)n-(CO)m-R8 which is preferably located in the position para to the bridge bond, in which A represents CH2, O or represents NR9, in which R9 represents hydrogen, (C 1-C4)-alkyl or (C3-C~)-cycloalkyl, or represents the group -(CH2)~,-(CO)m O-(C1-C4)-alkyl, n represents the number 0 or 1, m represents the number 1 or 2, R8 represents hydrogen, hydroxyl, OR1~, NR11R12, (C1_C8)_alkyl, (C3-Cg)-cycloalkyl, (C6-Clp)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to four identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C 1-C4)-alkyl, (C I-C4)-alkoxy, (C 1-C4)-alkoxyphenyl, (C3-Cg)-cycloalkyl, O-CO-R13, -CO-O-R14, -CO-NRi5R16, -NHCOR1~ and -NHCOOR1~, where R1~, Rtl, R12, R13, R14, R15, R16 and R1~ are identical or different and each represents hydrogen, benzyl, (C 1-C6)-alkyl or (C3-Cg)-cycloalkyl which for their Ix A 34 254-Foreign Countries IS -part are optionally mono- or polysubstituted by fluorine, chlorine, hydroxyl, amino, -CO-O(C t-C4)-alkyl, -NH-CO-O(C 1-C4)-alkyl, -O-CO-(Ci-C4)-alkyl, imidazolyl, hydroxyphenyl or (Ct-C4)-alkoxy, R4 and RS are identical or different and each represents hydrogen, halogen or (C1-C4)-alkyl, R6 represents chlorine, fluorine, bromine or has the meaning given for R8 and is identical to or different from this above substituent or represents the radical Rz° Rz~
Rzz in which R2~ and R2t together with the carbon atom to which they are attached form a carbonyl group, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C~-C4)-alkyl, (Ct-C4)-alkoxy or the radical -NR15R16 and R22 has the meaning of R8 and is identical to or different from this substituent, R~ represents hydrogen, and their salts.
Of particular importance are compounds of the general formula (I), in which Z represents oxygen or CH2, Ix A 34 254-Foreign Countries R! and R2 are identical or different and represent methyl, ethyl, propyl, isopropyl, chlorine, bromine, CF3, vinyl or cyclopropyl, where both substituents are located in the position ortho to the bridge bond, R3 represents the group -NR9-(CO)n.,-Rg, located in the position para to the bridge bond, where R9 represents hydrogen, (CI-C4)-alkyl or (C3-C~)-cycloalkyl, m represents 2, Rg represents (C,-C6)-alkyl, pyridyl, ORI~ or NR!lRl2, where Rl~, R!! and R!2 represent hydrogen, benzyl, (CI-C4)-alkyl or (C3-C6)-cycloalkyl, R4 and RS represent hydrogen, methyl, fluorine or chlorine, R6 represents hydrogen, hydroxyl, ORI~, NR!!Rl2, (CI-Ca)-alkyl, (C3-C6)-cycloalkyl, (C6-Ctp)-aryl, or represents a saturated, unsaturated or aromatic S-to 10-membered heterocycle having up to three identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C!-C4)-alkyl, (C!-C4)-alkoxy, (C3-Cg)-cycloalkyl, O-CO-Rl3, -CO-O-Rl4, -CO-~I5Rt6 and -NHCOORI~, where Rl~, R!!, Rl2, R13, R14~ R15~ R16 and R1~
are identical or different and each represents hydrogen, benzyl, (C!-C4)-alkyl or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (CI-C4)-alkoxy, Le A 34 254-Foreign Countries or represents the radical R2° R2~
~ R22 in which R2o and R21 together represent oxygen, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (Ct-C4)-alkyl, (Ct-C4)-alkoxy or the radical -NRt5Rt6 and R22 represents hydrogen, hydroxyl, ORto, NR11R12~ (Ct_C4)_alkyl, (C3-C6)-cycloalkyl, (C6-C tp)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to three identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, vitro, amino, CF3, (C~-C4)-alkyl, (Ct-C4)-alkoxy, (C3-Cg)-cycloalkyl, O-CO-Rt3, -CO-O-Rt4, -CO-NRt5Rt6 and -NHCOORt~, where Rto, Rtt, Rt2, R13, R14, R15, Rt6 and Ri~ are identical or different and each represents hydrogen, benzyl, (Ct-C4)-alkyl or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (Ct-C4)-alkoxy, R~ represents hydrogen, and their salts.
Of particular importance are compounds of the general formula (I), in which Le A 34 254-Fore Countries Z represents oxygen or CH2, R1 and R2 are identical or different and represent methyl, ethyl, propyl, isopropyl, chlorine, bromine, CF3, vinyl or cyclopropyl, where both substituents are located in the position ortho to the bridge bond, R3 represents the group -O-(CH2)n CO-Rg, located in the position para to the bridge bond, where R9 represents hydrogen, (C1-C4)-alkyl or (C3-C~)-cycloalkyl, n represents 1, 1S R8 represents (C,-C6)-alkyl, pyridyl, OR1~ or NRi tRl2, where RIB, Rtt and R12 represent hydrogen, benzyl, (Ct-C~)-alkyl or (C3-C6)-cycloalkyl, R4 and R5 represent hydrogen, methyl, fluorine or chlorine, R6 represents hydrogen, hydroxyl, OR1~, NR1 tRt2, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C6-Clp)-aryl, or represents a saturated, unsaturated or aromatic to 10-membered heterocycle having up to three identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C~-C4)-alkyl, (C1-C4)-alkoxy, (C3-Cg)-cycloa(kyl, O-CO-R13, -CO-O-R~4, -CO-NRt5R16 and -NHCOOR1~, where RIB, R11, R12, R13, R14~ R15, R~6 and Rte are identical or different and each represents hydrogen, benzyl, (C i-C4)-alkyl Le A 34 254-Forei~m Countries or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (C1-C4)-alkoxy, or represents the radical RZ° R2, ~ R22 in which R2o and R2t together represent oxygen, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C1-C4)-alkyl, (C1-C4)-alkoxy or the radical -NR~SR16 and R22 represents hydrogen, hydroxyl, ORto, NR11Rt2, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C6-Clp)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to three identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (Ct-C4)-alkyl, (C1-C4)-alkoxy, (C3-Cg)-cycloalkyl, O-CO-R13, -CO-O-Rt4, -CO-NRt5R16 and -NHCOOR1~, where Rio, R11, R12~ R13, R14~ R15~ R16 and R1~ are identical or different and each represents hydrogen, benzyl, (C1-Ca)-alkyl or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (Ct-C4)-alkoxy, R~ represents hydrogen, Le A 34 254-Foreign Countries and their salts.
Of particular importance are compounds of the general formula (I), in which Z represents CH2 or in particular oxygen, R1 and R2 are identical or different and represent methyl, ethyl, propyl, isopropyl, chlorine, bromine, CF3, vinyl or cyclopropyl, where both substituents are located in the position ortho to the bridge bond, R3 represents the group -O-(CH2)~-CO-R8 or preferably represents the group NR9-(CHz)~-(CO)m-Rg, in each case located in the position para to the bridge bond, where R9 represents -CHZ-CO-O-(Cj-C4)-alkyl-substituted (Ci-C4)-alkyl, (C3-C~)-cycloalkyl, -CO-CO-O-(C i-C4)-alkyl or, in particular, hydrogen, m represents the number 1 or, in particular, 2, n represents the number 1 or 0, R$ represents methyl, ethyl, n-propyl, isopropyl, n-, i-, s- or t-butyl, n-pentyl or n-hexyl, thiophenyl, pyridyl or represents the groups -CHZ-O-benzyl, OR1~ or NR11R12~
where R1~ represents hydrogen, or optionally hydroxyl-substituted straight-chain or branched alkyl having up to 7 carbon atoms, where R1~ and R~Z are identical or different and represent hydrogen, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, methoxy, ethoxy, n-propoxy, isopropoxy, t-butoxy, n-pentoxy, n-hexoxy Le A 34 254-Foreign Countries or straight-chain or branched alkyl having up to 6 carbon atoms, where alkyl for its part is optionally mono- or polysubstituted by identical or different substituents from the group consisting of hydroxyl, -CO-O(C~-C4)-alkyl, -NH-CO-O(C1-C4)-alkyl, imidazolyl and hydroxyphenyl, R4 and R5 represent methyl, fluorine or chlorine or, in particular, hydrogen, R~ represents hydrogen, hydroxyl, ORIO, NR1tR12, methyl, ethyl, n-propyl, isopropyl, n-, i-, s- or t-butyl, n-pentyl, (C3-C6)-cycloalkyl, (C6-Ctp)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to three identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, vitro, amino, CF3, (Ct-C4)-alkyl, (Ct-C4)-alkoxy, (C3-Cg)-cycloalkyl, O-CO-R13, -CO-O-Rt4, -CO-NR15R16 and -NHCOOR1~, where RIB, R11, R12, R13 R14, R15, R16 and R1~ are identical or different and each represents hydrogen, benzyl, (C1-C4)-alkyl or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (C1-C~)-alkoxy, or represents the radical R2° R2, ~ R22 in which R2~ and R21 together with the carbon atom to which they are attached form a carbonyl group, or are in each case identical or different and represent Le A 34 X54-Foreign Countries hydrogen, halogen, hydroxyl, (C1-C4)-alkyl, (CI-C4)-alkoxy or the radical -NR15R16 and R22 represents hydrogen, hydroxyl, ORIO, NR1ZR12, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C6-C1o)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to three identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C4)-alkyl, (Ct-C4)-alkoxy, (C3-Cg)-cycloalkyl, O-CO-R13, -CO-O-R14, -CO-NR15R16 and -NHCOORi~, where Rlo, R11~ R12~ R13, R14~ R15, R16 and RIB are identical or different and each represents hydrogen, benzyl, (Ci-C4)-alkyl or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (C1-C4)-alkoxy, R~ represents hydrogen, and their salts.
The abovementioned general or preferred radical definitions apply both to the end products of the formula (I) and, correspondingly, to the starting materials or intermediates required in each case for the preparation.
The individual radical definitions given in the respective combinations or preferred combinations of radicals may, independently of the particular radical combination given, also be replaced by radical definitions of any other combinations.
Particular preference is given to compounds of the formula (I) in which Z
represents oxygen.

Le A 34 254-Foreign Countries Particular preference is given to compounds of the formula (I) in which R3 represents the group NH-CO-CO-R8, located in the position para to the bridge bond, and R8 represents a group which, in the sense of a prodrug, can be degraded to a carboxylic acid or a salt thereof.
Particular preference is given to compounds of the formula (I) in which R', RS
and R' represent hydrogen.
Particular preference is given to compounds of the formula (I) in which Ri and R2 are both located in the position meta to one another and in particular both in the position ortho to Z and represent chlorine, bromine, trifluoromethyl, cyclopropyl and, in particular, methyl.
By way of example and by way of preference, the following individual compounds may be mentioned:
Compounds of the formula 1 in which X' has the meanings given in Table 1 (in the table, * indicates the point of attachment) HsC CHs O
N

L.e A 34 254-Foreign Countries Table 1 O O O O
O *~ ~
*~ OH *~ O~ *~N ~ H Il H O O
H ~ H
O _oQ O
*~ *\H~o~ *~H~O *\H I1 0 I'O
O ~ O
O
O o - - O O
*~N O *'H~o~ *~N~O~ *'H~Q
H O O
O
O o _ o *\H I1 0 *'H~O~ *'H~W/~/u' *~H~O~

O O
o -_ o O
*\N~O~ *'H I1 0 *'H~O~ *~N'~ O
0 0 ~ o O
O -o o CH3 O
*~N~'' Q *\H I1 0 *~N~O *\N~O
H !l O H ~
p O CH

O CHj O
*~ O~CH~ *~H~O~CH3 O *~
H~ CH3 O HsC CHI *~N p O
N ~ ~ H
O
O O _ O O
*\ ~O *'H I1 0 *'H I1 0 *~N~O
H I' H ~ ~O
O ~ O ~ O

Le A 34 254-Foreign Countries X1 Xt X1 - Xt p H3 ~O N
O O O *,N Ii.
*'N N *\H~O~~ *\H II CHI
H~ ~ p CHI O

o O o O~~ CH3 ~ ~ ~II~ *. ~O~/~/ z * O
*'H II N *\H~p~NHz H O NH 'H L1 1 _ NH2 O ~O ~~C//H ~3 o O O O CH3 *.N~ N *\ NH2 *, NCH *~N N~CH3 o ~ H H O
O O

*\ O NH3 *'N o o \ I *\N~N~CH3 *~N N~CH3 N ~H
H~ H o O H O
O

O
*~ NuCH3 *~ NCH *~N NUCH3 *~H~N~CH3 N N s O
H~ H H O
O O
O ~ O ~ O ~N O ~N N
N N *~ N
*~N NON *~N N~N~ *~N N~N~ N
H O H O H O H O
O ~ O N~ O NINA O N~
N / N~ ~N NH ~N NH *\ N\N N
*~N ~ *~N~ *~N N
H O H O H O H O
QQ 0'I 0II ~H, *\ ~O~O ~,\N~p~O~~H~ *~N~O~O.CH~ *.N~N~CH~
~CH3 H' ~~ H~ l~°~f H Ipl ~CH~
O

Le A 34 254-Forei~ Countries Xi Xt Xi Xt °II °~~ ° O ~H
*~N~O~O~~ t.H~O~/~,/~O/vCHa *' H ° o~ N *~N N
H O ~
v 'o H
I O
Individual compounds of the formula 2 in which XI has in each case the meanings given in Table I and, for each of the individual compounds 1 to 68, X2 has, instead of methyl as in formula 1, in each case the meanings given for XZ in Table 2:

~ O
/ ~/

Le A 34 254-Foreign Countries Table 2 x2 X2 X2 X2 H F CI Br *~CH *~CH3 *~CH

*~ *~CH3 *~~CH3 *~~CH3 * CH3 * CH3 *.
~CH3 *~ CH CF3 CH3 CHs CH3 CH
*~CF2H *~CFH2 * CH3 *\~CH3 * CH3 * CHs * CH3 * CH3 w CH ~H3 * CH3 H3C ~CH3 * * CH3 * CH3 *~~CH CH3 * CH3 CH3 3 CHs *~~I~'CHs CH3 * CH3 * CH3 * CH3 CH3 ~CH3 CH3 * CH3 Le A 34 254-Foreign Countries Individual compounds of the formula 3 in which Xl and X2 have in each case the meanings given in Table 1 and 2 and, for each of the individual compounds 1 to 2788, X3 has, instead of methyl as in formula 2, in each case the meanings given for X3 in Table 3 \ O ( \
N~ 3 ~ X~
H X

Table 3 H F Cl Br I *~CH *~CH3 *~CH

*~/ *\ /CH3 *~CH3 *~~CH3 CH3 C~H ''3 * CH3 * CH3 *~
~CH3 *~ CH CF3 * CH3 *~CF2H *~CFH2 CH3 *\~CH3 * CH3 CH3 ~CH3 CH
*~CH I \CH3 Le A 34 254-Foreign Countries H F Cl Br * CH3 H3C ~CH3 * * cH3 * CH CH3 * cH3 * CH3 CH3 CH3 *~~CH3 CH3 *~~CH3 - CH3 * CH3 CH3 \~CH3 CH3 * CH3 Individual compounds of the formula 4 in which XI, X2 and X3 have in each case the meanings given in Tables 1, 2 and 3 and, for each of the individual compounds 1 - 114 308, X4 has, instead of methyl as in formula 3, in each case the meanings given for X'~ in Table 4 Le A 34 254-Forei ~ Countries Table 4 H F C1 Br *~CH *~CH3 *~CH

CH3 * CH3 *~CH3 * CH3 ~CH3 * CHs * CH3 *~CF
CH3 *~ ~CH3 3 * CH
*~CF2H *~CFH2 CH3 * CH3 * CH3 CH3 * CH3 * CH
* CH ~Hg 3 CH

* CH3 H3C ~CH3 - * * CH3 * CHs * CH3 * CH3 CH3 CH3 * CH CHs *~./'~/CH3 Le A 34 254-Foreign Countries *~ _ of o O
* ~ \ * ~ \
* * / /
F
O
* ~ * \ * \ CH3 CH3 / ~ / ~ ,' * \

CH3 * \ CH3 * \ CI C!
* ~ \ ~ / ~ / * \
r * * ~ OCH3 OCH3 * CH

~ i * \ ~
ocH3 I /

* ~ CH3 * \ * \ * \
/ ~ / ~ / ~ /
H3C C( Le A 34 254-Foreign Countries * ~ CI * \ * \ C! * \
c! I '' I / I I
Ci /
CI
Ct ct ct * ~ * \ ocH3 ocH3 * \ F
~ -' * \ I
H~CO ~ /

* F * \ F F
F
I \ I / * \ * \ F
F I / I
F
* \ * ' \ OCH3 * \ OCH3 * ~ OCH
I / ~ I
CI ~'' ~C! OCH3 / H3C0 * I \ F * \ F * \ ~. oCH
I
F / I
F F
F
,,-' F
/ CI ,. CH3 * \ I * \ ~ * \ I * \
,- CH3 , I cH3 ~. H3C
* ~ ' * \ * \ ~ I
CH3 CH ~ 'CH3 * \
3 C'H3 Le A 34 254-Foreign Countries / * \ ~ /
* \ ~ * \

CI / OMe * \ I / * \ I
* \ I
F CI
OMe / Me0 /
* \ ~ * \ ( OMe * \ I OMe * \
OMe OMe OMe OMe Me0 / OMe MeO /
* \ t * \ ~ * \
OMe ~ F
F
OMe / F F F / F F / F
* \ ~ ~ I * \
F
F
F / / / CI CI
/
* \ ~ * \ CI * \
CI * \
CI
F
CI / CI CI CI / / Me * \ ~ / * \ ~ * \
m * \
CI
CI

Le A 34 254-Foreign Countries 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) R6 RS R' Rs RS , Y R
x + .r I ~ / , z, I _-~.. ti) 2 9 N /' 3' 7~ ~'~\~~ a R R ~r ~~~\~ a z R
R R R
(B) (~) ( where the substituents R1, R2, R3, R4, R5, R~ and R~ have the meanings given above and R3' has the meaning given for R3 or represents N02, NH2 or NPG, where PG represents a protective group, X and Y are in each case groups of opposite reactivity, where, for example, X
may be an electrophilic radical reacting with a nucleophilic Y substituent, and vice versa, Z' has the meaning given for Z or represents ~CHOH , Le A 34 254-Foreign Countries if appropriate in the presence of inert solvents and catalysts and if appropriate with isolation of the intermediates of the general formula (N), or directly, to give compounds of the formula (I).
Examples of catalysts which may be mentioned are coupling catalysts such as Pd andlor Cu compounds.
Examples of the reactive groups X and Y which may be mentioned are: halogen, hydroxyl, CH2Br, mercapto, CHO, Li, MgHal, Sn or boron derivatives.
The indoles of the general formula (II) which can be used according to the invention are known or can be prepared by known methods (compare, for example, Ozaki et al., Heterocycles, 1999, 51, S. 727-731, Harvey et al., J. Chem. Soc. 1959, 473;
Quadbeck et al., Hoppe-Seylers Z. Physiolog. Chem. 297 (1954) 229; Chen et al., J.
Org. Chem. 59 (1994), 3738).
The phenyl derivatives of the general formula (III) are likewise known or can be prepared by known methods (compare, for example, EP 580 550 A).
The reaction of the starting materials (II) with (III) is generally carried out under atmospheric pressure. However, the reaction can also be carned out under elevated or reduced pressure.
The reaction can be carried out in a temperature range of from -100°C
to 200°C, preferably between -78°C and 150°C, in the presence of inert solvents. Preferred inert solvents are: dimethyl sulphoxide (DMSO), diinethylformamide (DMF), tetrahydrofuran (THF), diethyl ether, etc.
Depending on the particular substituent pattern, in the reaction of (II) and (III) intermediates of the formula (IV) or (IV') may be formed in which, for example, the substituent R3 represents a nitro group or Z represents a CHOH group, which are Le A 34 254-Foreign Countries then, with or without isolation of these intermediates, reduced by customary methods to the corresponding amino groups or methylene groups, and can then be reacted further, by customary methods, with carboxylic acids or carboxylic acid derivatives, such as esters, anhydrides or halides, to give amide compounds in the formula (I).
The process according to the invention can be illustrated in an exemplary manner by the formula schemes below:

Le A 34 254-Foreign Countries Process variant (A) Rs Rs R, Rs Rs R, Y
DMSO. DMF etc. ~ ~ \ Z I
+ /- bas N ./ /
/ Rz NOz RT-t5o°C ~~ z NOz R Ra R R R
(11) (III) z.B. (IV') Rs Rs R, O) Z
i reduction ~ \ I GI m Rs -,~.. N I / -~.
Ra Rz / NHz R
pv°) (I) Process variant (B) HO R~ Rs Rs OH Rt Li + I
NPG / ~ / /
R N ~ ~NPG
R~ Ra Rz (II) (III) (IV') . Removal reduction f PG
2. e.g. s R
O "
(G) a CI m R (I) Depending on the meaning of the substituents Ri, R2, R4, R5, R6 and R~, it may be 10 expedient or necessary to vary these in the individual process steps, within the given range of meanings.

Le A 34 254-Forei~on Countries The precursors or intermediates of the formula (IV) which occur in the reaction of (II) and (III) and are represented in the formula scheme above by (IV') and (IV") are novel. Accordingly, this application also provides compounds of the general formula (IV) Rs Rs R, Z' (N) R,N R4 RZ / R3, in which R1, R2, R4, R5, R6 and R~ have the meaning given above for formula (I}, Z' has the meaning given for Z or represents CHOH, and R3' has the meaning given for R3 or represents NOZ, NH2 or NPG, where PG
represents a protective group, with the proviso that if Z' represents CH2, R3' does not represent N02, and that if Z' represents CH2, R3~ represents NH2, R1 and R2 represent (C1-C4)-alkyl, R'~ and RS represent H and R6 represents amino-substituted C3-C6-cycloalkyl, R~ does not represent hydrogen.

Le A 34 254-Foreign Countries In the present application, protective groups (PG) are understood as meaning groups in starting materials, intermediates and/or end products which protect the functional groups present, such as, for example, carboxyl, amino or hydroxyl groups, and which are customary in preparative organic chemistry. The groups protected in this manner can then be converted in a simple manner under known conditions into free functional groups.
The compounds of the formula (I) according to the invention have a surprising and useful spectrum of pharmacological activity and can therefore be used as versatile medicaments. In particular, they can be used for all indications which can be treated with natural thyroid hormones, such as, by way of example and by way of preference, depression, goitre or cancer of the thyroid gland. The compounds of the formula (I) according to the invention are preferably used to treat arteriosclerosis, hypercholesterolaemia and dyslipidaemia. Furthermore, it is also possible to treat obesity and cardiac insufficiency, and it is possible to achieve postprandial lowering of triglycerides.
The compounds are also suitable for treating certain respiratory disorders, i.e., in particular, pulmonary emphysema, and for medicinally promoting maturation of the lungs.
The compounds are furthermore suitable for treating Alzheimer's disease.
The compounds are furthermore suitable for treating osteoporosis, cardiac arrhythmias, hypothyroidism and skin disorders.
Moreover, the compounds can also be used for promoting and regenerating hair growth, and for treating diabetes.
The active compounds according to the invention allow further treatment alternatives and are a useful addition to the pharmaceutical prior an. Compared with the known Le A 34 254-Foreign Countries thyroid hormone preparations which have hitherto been used, the compounds according to the invention have an improved activity spectrum. They are preferably distinguished by high specificity, good compatibility and fewer adverse effects, in particular in the cardiovascular field.
The activity of the compounds according to the invention can be examined, for example, in vitro by the known T 3 promoter assay cell test, described below:
The test is carried out using 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, upstream of the luciferase gene, a minimal thymidine kinase promoter with a thyroid-hormone-responsive element (TRE) comprising two inverted palindromes of in each case 12 by and one 8 by spacer.
For the test, the cell cultures are sown in 96-well plates in Eagle's Minimal Essential Medium, with the following additives: glutamine, tricine, sodium pyruvate, non-essential amino acids, insulin, selenium and transferin. The cultures are grown at 37°C in a 10% CO~ atmosphere for 48 hours. Serial dilutions of test substance or reference compound (T3, T4) and the costimulator retinoic acid are then added to the test cultures, which are then incubated as above far a further 48 or 72 hours.
Each substance concentration is tested in four replications. To determine the luciferase, induced by T3 or other substances, the cells are then lyzed by addition of a triton- and luciferin-containing buffer and immediately measured luminometrically. For each compound, the ECSp is calculated (see Table 1).

Ix A 34 254-Foreign Countries Table 1 Example ECSp (nM]

3 15.4 16 57.5 2 71.5 4 4.9 4.6 In the in vivo test described below, the compounds according to the invention 5 Likewise have surprising advantageous properties:
Description of the test for finding pharmacologically active substances which lower the serum cholesterol in mice:
The substances to be examined in vivo for their serum-cholesterol-lowering action are administered orally to male mice having a body weight between 25 and 35 g.
One day prior to the start of the test, the animals are divided into groups with the same number of animals, generally n = 7-10. During the entire experiment, the animals have drinking water and feed ad libitum. The substances are administered orally once a day for 7 days. To this end, the test substances are dissolved 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. The dissolved substances are administered in a volume of 10 ml/kg of body weight using a stomach tube. Animals which were treated exactly in the same manner but were only given the solvent (10 ml/kg of body weight), without test substance, served as control group.

Le A 34 254-Foreign Countries Prior to the first substance administration, a blood sample is taken from each mouse by puncture of the retroorbital venus plexus to determine the serum cholesterol (prevalue). The test substance is then administered to the animals for the first time, using a stomach tube. 24 hours after the last substance administration (on the 8th day after the beginning of the treatment), once more a blood sample is taken from each animal by puncture of the retroorbital venus plexus to determine the serum cholesterol. The blood samples are centrifuged and, when the serum is obtained, the cholesterol is determined photometrically using an EPOS analyzer 5050 (Eppendorf-Geratebau, Netheler & Hinz GmbH, Hamburg). The determination is carried out using a commercial enzyme test (Boehringer Mannheim, Mannheim).
The effect of the test substances on the serum cholesterol concentration is determined by subtracting the cholesterol value of the 1st blood sample (prevalue) from the cholesterol value of the 2nd blood sample (after the treatment). The mean of the differences of all cholesterol values of one group is determined and compared to the mean of the differences of the control group.
Statistical evaluation is carried out using Student's t-test, after the variants have been checked for homogeneity.
Substances which lower the serum cholesterol of the treated animals in a statistically significant manner (p < 0.05) by at least 10°l0, compared to the value of the control group, are considered to be pharmacologically effective.
The activity of the compounds according to the invention can be examined, for example, in vitro by the known T 3 promoter assay cell test, described below:
A11 customary administration forms, i.e. oral, parenteral, inhalative, nasal, sublingual, rectal or external, for example transdermal, particularly preferably oral or parenteral, administration, are suitable for administering the compounds of the general formula Le A 34 254-Foreign Countries (I). In the case of parenteral administration, intravenous, intramuscular and subcutaneous administration, for example as subcutaneous depot, may be mentioned as being particularly preferred. Very particular preference- is given to oral administration.
To this end, the active compounds can be administered on their own or in the form of preparations. Suitable preparations for oral administration are, inter alia, tablets, capsules, pellets, sugar-coated tablets, pills, granules, solid and liquid aerosols, syrups, emulsions, suspensions and solutions. The active compound has to be present in such an amount that a therapeutic effect is obtained. In general, the active compound can be present in a concentration of from 0.1 to 100% by weight, in particular from 0.5 to 90% by weight, preferably from 5 to 80% by weight. In particular, the concentration of active compound should be 0.5 - 90% by weight, i.e.
the active compound should be present in amounts which are sufficient to achieve the dosage range indicated.
To this end, the active compounds can be converted in a manner known se into the customary preparations. This is carried out using inert nontoxic pharmaceutically suitable excipients, auxiliaries, solvents, vehicles, emulsifiers and/or dispersants.
Auxiliaries which may be mentioned are, for example: water, nontoxic organic solvents, such as, for example, paraffins, vegetable oils (for example sesame oil), alcohols (for example ethanol, glycerol), glycols (for example polyethylene glycol), solid excipients, such as natural or synthetic ground minerals (for example talc or silicates), sugars (for example lactose), emulsifiers, dispersants (for example polyvinylpyrrolidone) and lubricants (for example magnesium sulphate).
In the case of oral administration, tablets may, of course, also contain additives such as sodium citrate, together with fillers such as starch, gelatin and the like.
Aqueous preparations for oral administration may furthermore be mixed with flavour enhancers or colorants.

Ix A 34 254-Foreign Countries In the case of oral administration, preference is given to administering dosages of from 0.001 to 5 mg/kg, preferably from 0.005 to 3 mg/kg, of body weight per 24 hours.
The novel active compounds can be administered on their own and, if required, also in combination with other active compounds, preferably from the group of the CETP
inhibitors, antidiabetics, antioxidants, cytostatics, calcium antagonists, hypotensive agents, thyroid hormones, inhibitors of HMG-CoA reductase, inhibitors of HMG-CoA reductase gene expression, squalene synthase inhibitors, ACAT inhibitors, circulation-promoting agents, thrombocyte aggregation inhibitors, anticoagulants, angiotensin-II receptor antagonists, cholesterol absorption inhibitors, MTP
inhibitors, fibrates, niacin, anorectics, lipase inhibitors and PPAR agonists.
The embodiments below are meant to illustrate the invention in an exemplary manner, without limiting the scope of the invention.

Lx A 34 254-Foreign Countries Embodiments (starting materials) Example I
5-f 4-Nitro-2,6-bi sari fluorometh~phenoxy]-1 H-indole H, ~% F3C

3 g (22.5 mmol) of 5-hydroxyindole, 6.61 g (22.5 mmol) of 2,6-bistrifluoromethyl-4-nitrochlorobenzene and 3.43 g of potassium carbonate (24.8 mmol) are dissolved in 250 ml of DMSO, and the mixture stirred at 80°C for 3 hours. The mixture is diluted with water and ethyl acetate, the organic phase is extracted 3 times with sodium chloride solution and dried over sodium sulphate and the solvent is removed under reduced pressure. Chromatographic purification (toluene/cyclohexane = 1:1) gives 4.98 g (56%) of 5-[4-nitro-2,6-bis(trifluoromethyl)phenoxy]-1H-indole.
200 MHz 1H-NMR (DMSO-d6): 6.32, m, 1H; 6.80, dd, 1H; 6.88, m 1H; 7.36, m 2H;

8.86, s, 2H; 11.15, s, 1H.
Example II
4-(1H-Indol-5-yloxy)-3.5-bis(trifluoromethyl)aniline O
N

2 g (5.1 mmol) of 5-[4-nitro-2,6-bis(trifluoromethyl)phenoxy]-1H-indole are dissolved in 250 ml of ethyl acetate and hydrogenated at 4 bar using 200 mg of Le A 34 254-Foreign Countries Pd/carbon (10%). The mixture is filtered off with suction through kieselguhr and the solvent is removed under reduced pressure, giving 1.84 g (99%) of 4-(1H-indol-yloxy)-3,5-bis(trifluoromethyl)aniline.
200 MHz 1H-NMR (DMSO-d6): 6.00, s, 2H; 6.30, s, 1H; 6.66, m 2H; 7.22, s, 2H;
7.28, m, 2H; 11.00, s, 1H.
Examine III
5~2,6-Dimethyl-4-nitrophenoxy)-1H-indole N-H NOz 2.3 g (17.27 mmol) of 5-hydroxyindole, 3.2I g (17.27 mmol) of 2,4-dimethyl-3-chloronitrobenzene and 11.26 g of caesium carbonate (34.55 mmol) are dissolved in 200 ml of DMSO, and the mixture is stirred at room temperature for 12 hours.
The mixture is diluted with water and ethyl acetate, the organic phase is extracted 3 times with sodium chloride solution and dried over sodium sulphate and the solvent is removed under reduced pressure. This gives 2.63 g (54%) of 5-(2,6-dimethyl-4-nitrophenoxy)-1H-indole.
200 MHz 1H-NMR (DMSO-d6): 6.30, m, 1H; 6.72, m, 2H; 7.32, m, 2H; 8.12, s, 2H;
11.09, s, 1H.
Example IV
4-(1H-Tndol-5-yloxy)-3.5-dimethylanitine Le A 34 254-Foreign Countries _47_ N--~ ~ ./

2.61 g (9.25 mmol) of 5-(2,6-dimethyl-4-nitrophenoxy)-1H-indole in 100 ml of ethyl acetate are hydrogenated at 3 bar for 2 hours, using 261 mg of Pd on carbon (10%).
The mixture is filtered through kieselguhr and the solvent is removed under reduced pressure. This gives 2.33 g (99%) of 4-(IH-indol-5-yloxy)-3,5-dimethylaniline.
Rf = 0.49 (toluene/ethyl acetate = 4:1) Example V
5-(2,6-Dimethyl-4.-nitrophenoxy)-3-methyl-1H-indole O
N ~ / _/
H NOz 440 mg (3 mmol) of 3-methyl-1H-indol-5-ole, 567 mg (3 mmol) of 2,6-dimethyl-4-IS nitrochlorobenzene and 460 mg (3.3 mmol) of potassium carbonate are dissolved in ml of DMSO and stirred at 125°C for 48 hours. The mixture is diluted with water and extracted with dichloromethane and 3 times with ethyl acetate, the combined organic phases are dried over sodium sulphate and the solvent is removed under reduced pressure. Chromatographic purification gives 333 mg (37%) of 5-(2,6-dimethyl-4-nitrophenoxy)-3-methyl-1H-indole.
400 MHz 1H-NMR (DMSO-d6): 2.12, s, 3H; 2.20, s, 6H; 6.68, m, 2H; 7.11, m, 1H;
7.29, d, IH; 8.12, s, 2H; 10.73, s, 1H.

Ix A 34 254-Foreign Countries Example VI
3,5-Dimethyl-4-f(3-methyl-1H-indol-5- l~ylaniline O
N~ ' 510 mg (1.72 mmol) of 5-(2,6-dimethyl-4-nitrophenoxy)-3-methyl-1H-indole in 150 ml of ethyl acetate are hydrogenated at a hydrogen pressure of 3 bar for 2 hours, using 510 mg of Pd/C (10%). The mixture is diluted with THF and filtered through kieselguhr and the solvent is removed under reduced pressure. This gives 458 mg (99%) of 3,5-dimethyl-4-[(3-methyl-1H-indol-5-yl)oxy]aniline.
200 MHz 1H-NMR (DMSO-d6): 1.92, s, 6H; 2.10, s, 3H; 4.81, s, 2H; 6.32, s, 2H;
6.60, m, 2H; 7.05, s, 1H; 7.21, d, 1H; 10.59, s, 1H.
Example VII
3-Isopropyl-5-(4-ni tro-2.6-bi stri fl uoromethylphenoxy)-1 H-indole N

346.0 mg (1.97 mmol) of 5-hydroxy-3-isopropylindole are dissolved in 4 ml of dimethyl sulphoxide, 300.18 mg (2.17 mmol) of solid potassium carbonate are introduced and 579.63 mg (1.97 mmol) of 2,6-bistrifluoromethyl-4-nitro-chlorobenzene are then added slowly, over a period of one hour. Immediately afterwards, the mixture is partitioned between 20 ml of water and 30 ml of ethyl acetate; the ethyl acetate phase is separated off and the aqueous phase is extracted Le A 34 254-Foreign Countries three more times with ethyl acetate. The combined ethyl acetate extracts are washed twice with sodium chloride solution, dried over sodium sulphate and concentrated to give an oil. The oily residue is dissolved in 4 ml of cyclohexane/ethyl acetate (9:1), applied to 200 ml of dry Si02 and then eluted with cyclohexane in a gradient mode, with addition of ethyl acetate.
Yield: 6.48 mg (75.8%) Rf: 0.23 (cyclohexane:ethyl acetate = 9:1) HPLC: rt (%) = 5.28 (98.9); 1% HC104/acetonitrile Example VIII
4-(3-Isoero_pyl-1H-indol-5-~y)-3,5-bistrifluoromethYlphe ~lamine 648.0 mg (1.5 mmol) of 3-isopropyl-5-(4-nitro-2,6-bistrifluoromethylphenoxy)-indole are dissolved in 14 g of ethanol p.a., admixed with 210 mg of palladium on activated carbon (5%) and hydrogenated at hydrostatic hydrogen pressure for 42 hours. The palladium catalyst is filtered off with suction through Si02, the filtercake is washed with ethanol and the filtrate is concentrated to give an oil. The crude product is dissolved in about 50 ml of toluene, applied to about 200 ml of dry silica gel and eluted initially with a mixture of 490 ml of toluene/10 ml of ethyl acetate and then with a mixture of 480 ml of toluene/20 ml of ethyl acetate. The eluate is concentrated, dissolved in a little dichloromethane and reconcentrated, resulting in partial crystallization.
Yield: 467 mg (76.9%) Rf: 0.43 (toluene:ethyl acetate = 9:1) Le A 34 254-Foreign Countries HPLC: rt (%) = 4.86 (99.36);
1% HC104/acetonitrile Example IX
3-(4-Fluorobenzyl)-5-f4-vitro-2,6-bis(trifluoromethyl)phenoxyl-1H-indole F
L~ /

O

100 mg (0.41 mmol) of 3-(4-fluorobenzyl)-1H-indol-5-0l are dissolved in 5 ml of DMSO and, at room temperature, admixed with 63 mg (0.46 mmol) of potassium carbonate and then with 121 mg (0.41 mmol) of 2-chloro-S-vitro-1,3-bis(trifluoromethyl)benzene. The mixture is stirred at room temperature for 5 h. The mixture is added to sat. ammonium chloride solution and extracted 3 times with ethyl acetate, and the combined organic phases are washed once with sat. NaCI
solution, dried over sodium sulphate and concentrated using a rotary evaporator. The residue is purified by chromatography (cyclohexane/ethyl acetate=10:1). This gives 140 mg (62%) of 3-(4-fluorobenzyl)-5-[4-vitro-2,6-bis(trifluoromethyl)phenoxy]-1H-indole.
300MHz'H-NMR (CDC13): 3.95, s, 2H; 6.46, d, 1H; 6.87, m, SH; 7.10, m, 2H;
7.96, s, broad, 1H; 8.80, s, 2H.

Le A 34 254-Foreign Countries Example X
4-! f3-(4-Fluorobenz~)-1H-indol-5-ylloxyl-3 5-bis(trifluoromethyl)aniline F

331 mg (1.57 mmol) of tin dichloride dihydrate are added to 5 ml of conc. HCI, and the mixture is heated to about 50°C. 122 mg (0.245 mmol) of 3-(4-fluorobenzyl)-5-[4-nitro-2,6-bis(trifluoromethyl)phenoxy]-1H-indole are then added in one portion.
The suspension is heated at about 70°C overnight and then allowed to cool to room temperature. The mixture is poured into water, made alkaline using 1N NaOH and extracted twice with ethyl acetate, and the combined organic phases are washed once with sat. NaCI solution, dried, concentrated using a rotary evaporator and dried under reduced pressure.
300MHz ~H-NMR (CDC13): 3.95, s, 2H; 4.00, s, broad, 2H; 6.45, d, 1H; 6.84, m, 4H;
7.12, m, 6H; 7.88, s, broad,lH.
Example XI
5-(2 6-Dibromo-4-nitrophenoxy)-3-(4-fluorobenzyl)-1H-indole F
Br N ~ i ~ i Br N02 Le A 34 254-Foreign Countries 100 mg (0.41 mmol) of 3-(4-fluorobenzyl)-1H-indol-5-0l are dissolved in 5 ml of DMSO and, at room temperature, admixed with 63 mg (0.46 mmol) of potassium carbonate and then with 124 mg (0.41 mmol) of 2-fluoro-5-vitro-1,3-dibromobenzene. The mixture is stirred at room temperature for 5 h and then poured into sat. ammonium chloride solution and extracted 3 times with ethyl acetate.
The combined organic phases are washed once with sat. NaCI solution, dried over sodium sulphate and concentrated using a rotary evaporator. The residue is purified by chromatography (cyclohexane/ethyl acetate=10:1). This gives 142 mg (62%) of 5-(2,6-dibromo-4-nitrophenoxy)-3-(4-fluorobenzyl)-1 H-indole.
300MHz ~H-NMR (CDC13): 4.02, s, 2H; 6.60, d, 1H; 6.93, m, 4H; 7.18, m, 2H;
7.35, d, 1H; 8.02, s, broad, 1H; 8.53, s, 2H.
Example XII
3,5-Dibromo-4-1 ~3-(4-fluorobenzyl)-1H-indol-5-ylloxy)aniline F

320 mg (1.42 mmol) of tin dichloride dehydrate are added to 5 ml of conc. HCI, and the mixture is heated to about SO°C. 123 mg (0.245 mmol) of 5-(2,6-dibromo-4-nitrophenoxy)-3-(4-fluorobenzyl)-1H-indole are then added in one portion. The suspension is heated at about 70°C overnight and then allowed to cool to room temperature. The mixture is poured into water, made alkaline using 1N NaOH and extracted twice with ethyl acetate, and the combined organic phases are washed once Le A 34 254-Foreign Countries with sat. NaCI solution, dried, concentrated using a rotary evaporator and dried under reduced pressure.
300MHz ~H-NMR (CDC13): 3.71, s, broad, 2H; 3.92, s, 2H; 6.62, d, 1H; 6.89, m, 6H;
7.18, m, 3H; 7.87, s, broad, 1H.
Example XIII
ten-Butyl 4-fll-ftert-but~(dimeth l~il~1-3-isopropyl-1H-indol-5-yll(hydrox~
methyll-3,5-dimethylphenylcarbamate OH
O
N / / N_ _O
-Si-. H
0.87 ml of methyllithium (1.6M in diethyl ether, 1.39 mmol) is initially charged in 1 ml of ether and, at -78°C, admixed with 400 mg (1.33 mmol) of tent-butyl 4-bromo-3,5-dimethylphenylcarbamate (dissolved in 0.53 ml of ether). The mixture is stirred for 20 min, 0.94 ml of tert.-butyllithium (1.7M in pemane, 1.59 mmol) are added slowly, and the reaction mixture is stirred at -78°C for 30 min.
A solution of 321 mg (1.07 mmol) of 1-[ten-butyl(dimethyl)silyl]-3-isopropyl-1H-indole-5-carbaldehyde in 0.5 ml of ether is then added dropwise, and the mixture is stirred at -78°C for 1.75 h. The cooling bath is removed, and NH4C1 solution is added. The mixture is poured into diethyl ether and washed with saturated NaCI solution.
The organic phase is dried over sodium sulphate and concentrated using a rotary evaporator. Chromatographic purification (cyclohexane/ethyl acetate) gives 46 mg (13%) of tert-butyl 4-[{ 1-[tent-butyl(dimethyl)silyl]-3-isopropyl-1H-indol-5-yl } (hydroxy)methyl]-3,5-dimethylphenylcarbamate.
Rf= 0.38 (cyclohexane/ethyl acetate=3:1) L,e A 34 254-Foreign Countries Example XIV
4-f (3-Isopropyl-1H-indol-5-yl)methyll-3.5-dimethylaniline At 0°C, a solution of 41 mg (0.078 mmol) of ten-butyl 4-[{ 1-[tert-butyl(dimethyl)silyl]-3-isopropyl-1H-indol-5-yl } (hydroxy)methyl]-3,5-dimethylphenylcarbamate in 1 ml of dichloromethane is added dropwise over a period of 30 min to a solution of 55 mg (0.47 mmol) of triethylsilane and 1 mg of trimethylsilyl triflate in 5 ml of dichloromethane. The mixture is stirred at 0°C for 30 min and then at room temperature for 60 min. The mixture is poured into an NaHC03 solution and extracted with dichloromethane, and the extract is dried over sodium sulphate and concentrated using a rotary evaporator. The resulting crude product is stirred in 10 ml of a 10% strength solution of trifluoroacetic acid in dichloromethane overnight. The mixture is neutralized using NaHC03 solution, and the organic phase is dried and concentrated using a rotary evaporator. This gives 11 mg of 4-[(3-isopropyl-1H-indol-5-yl)methylJ-3,5-dimethylaniline.
300MHz ~H-NMR (CDC13): 1.30, d, 6H; 2.26, s, 6H; 3.11, hept, 1H; 4.12, s, 2H;
5.71, s, broad, 2H; 6.66, dd, 1H; 6.92, s, 1H; 7.02, s, 2H; 7.20, m, 2H; 7.78, s, broad, 1H.
Example XV
3-Isopropyl-5-(4-nitro-2,6-dibromophenoxy)-1 H-indole I/
H ~ Br ~ 'N~2 Le A 34 254-Foreign Countries Similarly to the procedure of Example VII, 546.7 mg (3.12 mmol) of 5-hydroxy-3 isopropyl-indole are reacted in dimethyl sulphoxide with 932.5 mg (3.12 mmol) of 2,6-dibromo-4-nitrofluorobenzene and 474.3 mg (3.43 mmol) of potassium carbonate at room temperature for 3 hours. Chromatographic purification of the crude product is carried out using cyclohexane/ethyl acetate (from 9.5 : 0.5 to 9:1).
Yield: 1056.6 mg (73.3%) Rf: 0.47 (cyclohexane : ethyl acetate = 8:2) MS (EI): 454 ([M+H]+, 44%) NMR (300 MHz, CDC13): 8=1.3 (d, 6H); 3.09 (quin, 1H); 6.77 (dd, 1H); 6.95 (d, 1H); 7.0 (d, 1H); 7.28 (d, 1H); 7.89 (broad s, 1H); 8.51 (s, 2H) ppm.
Example XVI
1S 4- 3-Isopropyl-1H-indol-5-Yloxy)-3,5-dibromophenylamine Br N
H Br NH2 1.32 g (5.67 mmol) of tin(II) chloride dehydrate are added to a solution of 0.51 g (1.13 mmol) of the indole derivative from Example XV in 10 ml of dimethylformamide and 1.0 ml of water, and the mixture is stilted at 50°C for 3 hours. After cooling to room temperature, the reaction solution is then admixed with SO ml of saturated sodium bicarbonate solution and 50 ml of ammonium chloride solution and extracted four times with ethyl acetate. The organic phases are combined, extracted once with sodium chloride solution and dried over sodium sulphate, and the solvent is removed under reduced pressure. The residue is purified by silica gel chromatography using toluene/ethyl acetate (9:1).
Yield: 0,346 g (69.6%) Rf: 0.58 (toluene : ethyl acetate = 8:2) MS (ESI): 425 ([M+H]+, 100%) Le A 34 254-Foreign Countries NMR (300 MHz, db-DMSO): 8=1.21 (d, 6H); 2.97 (quin, 1H); 5.55 (broad s, 2H);
6.61 (dd, 1H); 6.71 (d, 1H); 6.9 (s, 2H); 7.04 (d, 1H); 7.22 (d, 1H); 10.68 (s, 1H) ppm.
S Example XVII
3-Isopropyl-5-(4-nitro-2,6-divinylphenoxy)-1 H-indole / ~ \ O ~ \
H~ i N02 500 mg (1.10 mmol) of the indole derivative from Example XV are dissolved in 33 ml of toluene, and 1745.7 mg (5.51 mmol) of tributylvinylstannane and 508.9 mg (0.44 mmol) of tetrakis-(triphenylphosphine)-palladium are added. Under argon, the solution is boiled at reflux for 20 hours; the reaction solution is then cooled and applied to 200 ml of dry silica gel. Elution is carried out using 1000 ml of toluene and 500 ml of toluene/ethyl acetate (9:1), and the desired fractions are concentrated under reduced pressure.
Yield: 321.4 mg (80.9%) Rf: 0.65 (toluene : ethyl acetate = 9:1) MS (EI): 348 ([M]+, 64%) NMR (300 MHz, CDCI3): b=1.27 (d, 6H); 3.02 (quin, 1H); 5.32 (d, 2H); 5.86 (d, 2H); 6.73 (dd, 1H); 6.83-6.91 (m, 3H); 6.95 (d, 1H); 7.24 (s, 1H); 7.82 (broad s, 1H);
8.41 (s, 2H) ppm.
Example XVIII
4-(3-Isopropyl-1H-indol-5-yloxy)-3,5-divinylphe~lamine O
\ I NH
z Le A 34 254-Fore~n Countries Similarly to the procedure of Example XVI, 100 mg (0.29 mmol) of the vitro compound from Example XVII in 2 ml of DMF and 0.2 ml of water are stirred with 323.8 mg (1.44 mmol) of tin(II) chloride dihydrate at room temperature overnight.
The crude product is purified by silica gel chromatography using toluene/ethyl acetate (9.5 : 0.5).
Yield: 70.6 mg (77.2%) R f: 0.38 (toluene : ethyl acetate = 9:1 ) MS (ESI): 319 ([M+H]+, 100%) NMR (200 MHz, CDC13): 8=1.27 (d, 6H); 3.04 (quip, 1H); 3.67 (broad s, 2H);
5.11 (dd, 2H); 5.65 (dd, 2H); 6.72-6.91 (mm, SH); 6.90 (s, 2H); 7.2 (d, 1H); 7.75 (broad s, 1H) ppm.
1 S Example XIX
3-Isopropyl-5-(4-vitro-2,6-dicyclopronylphenoxy)-1 H-indole / ~ \ O
H~ ~ N02 Under argon (not a stream of argon), 102.2 mg (0.29 mmol) of the divinyl derivative from Example XVII are mixed at 0°C with 30 m1 (30.0 mmoi) of a diazomethane/diethyl ether solution (prepared from Diazald). After the mixture has warmed to room temperature, it is allowed to stand for 2 days, and diazomethane is then flushed out in a stream of argon. The residue that remains is dissolved in 30 ml of xylene and boiled at reflux (bath temperature: 160°C) for 2.5 hours.
The xylene solution is concentrated and the residue is then dissolved in toluene and applied to 100 ml of dry silica gel. Elution is carned out using 500 ml of toluene, and the eluate is concentrated to dryness.
Yield: 70.8 mg (64.1 %) MS (DCI): 394 ([M+NH~]+, 100%) HPLC: rt (%) = 5.64 (93.1 %) Le A 34 254-Foreign Countries 0.01_mol. H3P04/acetonitrile Kromasil column C 18 (60 x 2 mm) Flow rate 0.75 ml/min, 210 rm.
Example XX
4-(3-Isoprogvl-1H-indol-5 yloxy)-3,5-dicyclopropyl-phenylamine N~ ~ NH2 H
The preparation is carried out similarly to the procedure of Example XVI by reacting 70.0 mg (0.19 mmol) of the nitro compound from Example XIX with 0.21 g (0.93 mmol) of tin(II) chloride dehydrate at 40°C for 2 hours and then at 55°C for 1 hour. The crude product (60.6 mg) is chromatographed on a YMC-polyamine II
column using tent-butyl methyl ether/methanol (97.5 : 2.5) at a flow rate of ml/min.
Yield: 45.0 mg (69.1%) MS (ESI): 347 ([M+H]+, 100%) HPLC: rt (%) = 4.76 (99.7%) tert-butyl methyl ether/methanol (95:5) YMC polyamine II column Sp,m (250 x 4 mm), 210 nm Flow rate 1 ml/min.

Le A 34 254-Foreign Countries Example XXI
3-~2-tert-Butoxycarbonylaminoethyl)-5-(4-nitro-2,6-bis-trifluoromethyl-phenoxy)-1H-indole O
HN- C-O

The preparation is carried out similarly to the procedure of Example VII by reacting 643.7 mg (1.7 mmol) of 1,3-bis-(2-tert-butoxycarbonyl)-3-aminoethyl-5-hydroxy indoline and 499.3 mg ( 1.7 mmol) of 2,6-bis-trifluoromethyl-4-nitro-chlorobenzene in 6 ml of dimethyl sulphoxide in the presence of 258.6 mg (1.87 mmol) of potassium carbonate, the indoline being rearomatized, with elimination of the tert butoxycarbonyl protective group at the indole nitrogen.
Yield: 410.5 mg (44.6%) MS (DCI): 551 ([M+NH4]+, 100%) Rf : 0.64 (toluene:ethyl acetate = 8:2) HPLC: rt (%) = 5.17 (98.6%) 1% HC10~/acetonitrile Kromasil column C18 (60 x 2 mm) Flow rate 0.75 ml/min, 210 nm.
Exampie XXII
3-(2-tert-Butox~carbon~aminoeth 1~-amino-2,6-bis-trifluoromethyl-phenoxy)-1 H-indole O
HN- C'O

/ ~ \ O

Similarly to the procedure of Example VIII, 396.2 mg (0.74 mmol) of the nitro compound from Example XXI in 30 mI of ethanol are hydrogenated with hydrogen for 2 days, using 80 mg of 10% palladium on activated carbon. The hydrogenation Le A 34 254-Foreign Countries solution is then filtered off with suction through 15 ml of silica gel, the filter residue is washed with ethanol and the filtrate is concentrated under reduced pressure. The concentrate is dissolved in 20 ml of toluene and the mixture is purified by chromatography on 250 ml of silica gel using toluene with added ethyl acetate.
Yield: 371 mg (97.6%) Rf: 0.28 (toluene : ethyl acetate = 8:2) MS (ESI): 387 ((M+H]+, I00%) IO NMR (300 MHz, CDCI3): 8=1.43 (s, 9H); 2.82 (t, 2H); 3.38 (m, 2H); 4.0 (broad s, 2H); 4.56 (broad s, 1H); 6.75 (dd, IH); 6.8 (d, 1H); 7.0 (d, 1H); 7.15 (s, 2H); 7.22 (d, 1 H); 7.9 (s, 1 H) PPm.
Example XXIII
3-Isopropel-5-(4-nitro-2,6-dimethyl-phenoxy)-1H-indote O
I ~ I ~
N- ~'' ~ ~NOZ
H
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 solid potassium carbonate are introduced and 9.94 g (58.76 mmol) of 3,5-dimethyl-4-fluoronitrobenzene are then added. For 2 hours, the reaction solution is stirred at 100°C under argon. The solution is then cooled to room temperature and 100 ml of ethyl acetate and 600 ml of H20 are added; after phase separation, the ethyl acetate is separated off and the aqueous phase is reextracted twice with ethyl acetate. The combined organic phases are washed twice with sodium chloride solution, dried over sodium sulphate, filtered and concentrated to dryness.
The residue is purified by silica gel chromatography using cyclohexane/ethyl acetate (10:1).
Yield: 11.96 g (62.8%) MS (DCI): 342 ([M+NI-h]+, I00%) Rf = 0.26 (cyclohexane : ethyl acetate = 8:2) Le A 34 254-Foreign Countries 300 MHz 1H-NMR (CDCl3): 1.28 (d, 6H); 2.24 (s, 6H); 3.05 (quip, 1H), 6.72 (dd, 1H); 6.84 (d, 1H); 6.99 (d, IH), 7.27 (d, 1H); 7.87 (s, 1H), 8.03 (s, 2H).
The following compounds (Examples XXN and XXV) are prepared similarly to the procedure of Example XXI>Z:
Example XXIV
3-sec-B ut~-5-(4-nitro-2,6-dimethylphenoxy)- I H-indole Reactants:
5 g (26.42 mmol) of 5-hydroxy-3-sec-butyl-indole 8.94 g (52.84 mmol) of 3,5-dimethyl-4-fluoronitrobenzene 4.02 g (29.06 mmol) of potassium carbonate in 60 ml of DMSO
Yield: 2.27 g (22.7%) MS (LC method, ES+): 339 ([M+H]+, 100010) Rf = 0.43 (cyclohexane: ethyl acetate = 8:2) HPLC rt = 5.80 (89.2%) 0.01 M H3P0~/acetonitrile Kromasil CI8 (60x2 mm) Flow rate: 0.75 ml/min, 2I0 nm Example XXV
3-Isobutyt-5-(4-vitro-2,6-di methylphenoxy)-1 H-indole H

Le A 34 254-Foreign Countries Reactants:
g (22.84 mmol) of 5-hydroxy-3-isobutyl-indole 3.86 g (22.84 mmol) of 3,5-dimethyl-4-fluoronitrobenzene 3.47 g (25.12 mmol) of potassium carbonate 5 in 100 ml of DMSO
Yield: 4 g (51.7%) R f = 0.28 (toluene : ethyl acetate = 9:1 ) Example XXVI
3-Isobutyl-5-(4-vitro-2,6-bis-trifluorometh ELI-phenoxy)-1H-indole H
2.0 g (10.57 mmol) of 5-hydroxy-3-isobutyl-indole are dissolved in 20 ml of DMSO, 1.6I g ( 11.62 mmol) of solid potassium carbonate are introduced and 2.79 g (9.50 mmol) of 2,6-bis-trifluoromethyl-4-nitrochIorobenzene are then introduced a little at a time. The mixture is stirred at room temperature for 30 min and then diluted with water and ethyl acetate, the ethyl acetate phase is separated off and the aqueous phase is extracted three more times with ethyl acetate. The combined organic phases are washed with sodium chloride solution, dried over sodium sulphate, filtered and concentrated using a rotary evaporator. The residue is purified by silica gel chromatography using cyclohexane/ethyl acetate (9:1).
Yield: 0.583 g (12.4%) Rf = 0.76 (toluene : ethyl acetate = 4:1) The following compounds (Examples XXVII to XXXI) are prepared similarly to the procedure of Example XXVI:

Le A 34 254-Foreigyn Countries -b3-Example XXVII
3-sec-Butyl-5-(4-vitro-2 6-bis-trifluoromethyl-phenox~-1H-indole H
Reactants:
2.09 g (8.9 mmol) of 5-hydroxy-3-sec-butyl-indole 1.3 g (4.45 mmol) of 2,6-bis-trifluoromethyl-4-vitro-chlorobenzene 1.35 g (9.79 mmol) of potassium carbonate in 20 ml of DMSO
Yield: 1.38 g (80.2%) Rf= 0.4 (cyclohexane : ethyl acetate = 4:1) MS (EI): 446 (M+, 30%) HPLC: rt = 5.54 (80.2%) 0.01 M H3P0~/acetonitrile Kromasil column C 18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Example XXVIII
3-(4-FluoroQhen~rl)-5-(4-vitro-2,6-bis-trifluoromethyl-phenox~-1H-indole F

i Reactants:
250 mg (1.10 mmoi) of 5-hydroxy-3-(4-fluorophenyl)-indole 320 mg (I.20 mmol) of 2,6-bis-trifluoromethyl-4-vitro-chlorobenzene 170 mg (1.21 mmol) of potassium carbonate in 6 ml of DMSO

Le A 34 254-Foreign Countries Yield: 135 mg (25.3%) MS (EI): 484 ((M+], 100%) Rf = 0.27 (cyclohexane/ethyl acetate = 8:2) HPLC rt = 5.24 (93.6%) S 0.5 % HCIO~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate : 0.75 ml/min; 210 nm Example XXIX
3-Methyl-5-(4-vitro-2,6-bis-trifluoromethyl-phenoxy)-1H-indole O
I ~ I ~

H
Reactants:
960 mg (6.51 mmol) of 5-hydroxy-3-methyl-indole 1.91 g (6.51 mmol) of 2,6-bis-trifluoromethyl-4-vitro-chlorobenzene 990 mg (7.17 mmol) of potassium carbonate in 15 ml of DMSO
Yield: 554 mg (20.6%) MS (LC method, ES-): 403 ([M-H)-, 100%) HPLC rt = 4.99 (97.9%) 0.01 M H3P04/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Rf = 0.25 (cyclohexane : ethyl acetate = 8:2) Le A 34 254-Foreign Countries Example XXX
3-(Methoxycarbonylmethyl)-5-(4-ni tro-2.6-bi s-tri fl uoromethyl-phenoxy)-1 H-indole O
z H
Reactants:
1.00 g (4.87 mmol) of 5-hydroxy-3-(methoxycarbonylmethyl)-indole 0.715 g (2.43 mmol) of 2,6-bis-trifluoromethyl-4-vitro-chlorobenzene 0.74 g (5.36 mmol) of potassium carbonate in 10 ml of DMSO
Yield: 1.18 g (50.7%) MS (EI): 462 ([MJ+, 49%) HPLC rt = 4.87 (97.1 %) 0.01 M H3PO~/acetonitrile Kromasil column C 18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Example XXXI
Methyl (DL)-2-acetylamino-3-f5-(4-vitro-2~6-bis-trifluoromethyl_phenoxy)-1H-indol-3-yll-propionate O
HN
NOz Reactants:
0.5 g (1.81 mmol) of DL-N-acetyl-5-hydroxy-tryptophane methyl ester 0.265 g (0.903 mmol) of 2,6-bis-trifluoromethyl-4-vitro-chlorobenzene Le A 34 254-Foreign Countries 0.28 g (1.99 mmol) of potassium carbonate in 9 m1 of DMSO
Yield: 0.25 g (22.7%) S MS (ESI): 534 ([M+H]+, 35%a) HPLC rt = 4.56 (87.4%) 0.5% HClO4/acetonitrile Kromasil column C18 (60x2 mm) Flow rate : 0.75 ml/min, 210 nm Example XXXII
Methyl (DL)-2-acetylamino-3-f5-~4-nitro-2,6-dibromophenoxy)-1H-indol-3-y11-propionate O
H
Reactants:
1.00 g (3.60 mmol) of DL-N-acetyl-5-hydroxy-tryptophan methyl ester 1.08 g (3.60 mmol) of 2-fluoro-5-nitro-1,3-dibromobenzene 0.55 g (3.96 mmol) of potassium carbonate in 30 ml of DMSO
Yield: 1.7 g (76%) MS (LC method, ES+): 556 ([M+H]+, 100%) R f = 0.63 (dichloromethane/methanol = 9:1 ) 300 MHz'H-NMR (CDC13) : 1.96 (s, 3H); 3.22 (d, 2H); 3.69 (s, 3H); 4.9 (sext, 1H);
5.96 (d, 1H); 6.74 (dd, 1H); 6.88 (d, 1H); 7.01 (d, 1H); 7.29 (d, 1H); 8.15 (broad s, 1H); 8.53 (s, 2H).

Le A 34 254-Foreign Countries Example XXXIII
4- 3-Isobu~l-1H-indol-5-yloxy)-3,5-dimethyl-phenylamine NHZ
H
4.0 g (11.82 mmol) of the nitro compound from Example XXV are dissolved in 80 ml of methanol/ethanol (1:1), admixed with 210 mg of palladium on activated carbon (10%) and hydrogenated overnight at a hydrogen pressure of 3 bar. The palladium catalyst is filtered off with suction through kieselguhr, the filtercake is washed with ethanol and the filtrate is concentrated under reduced pressure.
The crude product is directly reacted further.
Yield: 0.151 g (78.4%) MS (DCI): 309 ([M+H]+, 100%) Rf = 0.32 (toluene : acetonitrile = 9:1) HPLC rt = 3.86 (95.9%) 0.01 M H3P04/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm The following compounds (Examples XXXIV to XL) are prepared similarly to the procedure of Example XXXIII:
Example XXXIV
4-(3-Isopropyl-1H-indol-5-foxy)-3,5-dimethyl-phenYlamine NHZ
H

Le A 34 254-Foreign Countries Reactants:
11.95 g (36.85 mmol) of the nitro compound from Example XXITI
550 mg of palladium/activated carbon (10%) 500 ml of a methanol/ethanol mixture 3 bar, hydrogen Yield: 10.75 g (97.9%) MS (DCI): 295 ([M+H)+, 100%) Rf = 0.36 (toluene : ethyl acetate = 9:1 ) HPLC rt = 4.15 (98.9%) 0.5% HC104/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Example XXXV
4-(3-sec-Butyl-1H-indol-5-yloxy)-3,5-dimethyl-nhenylamine H
Reactants:
1.67 g (4.935 mmol) of the nitro compound from Example XXIV
167 mg of palladium/activated carbon (10%) in 395 ml of ethanol 3 bar, hydrogen Yield: 1.522 (100%) MS (ESI): 309 ([M+H)+, 47%) HPLC rt = 4.26 (86.5%) 0.5% HCIO~/acetonitrile Kromasil column C 18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Le A 34 254-Foreign Countries Example XXXVI
4- 3-Isobutyl-1H-indol-5-yloxy)-3.5-bis-trifluoromethyl-phenylamine H
Reactants:
0.583 g (I.3I mmol) of the vitro compound from Example XXVI
58 mg of palladium/activated carbon (10%) in 100 ml of methanol 3 bar, hydrogen Yield: 543 mg (99.9%) Rf= 0.58 (toluene : ethyl acetate = 4:1) Example XXXVII
4~3-sec-Butyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenylamine O
! ~ I, H
Reactants:
1.08 g (2.42 mmol) of the vitro compound from Example XXVII
101 mg of palladium/activated carbon (10%) in 36 m1 of ethanol p.a.
3 bar, hydrogen Yield: 0.869 g (89.5%) MS (ESI): 417 ([M+H]+, 100%) HPLC rt = 5.08 (89.5%) 0.5% HCIO~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Ix -A 34 254-Foreign Countries Example XXXVIII
4-f3~4-Fluorophenyl-1H-indol-5-Yloxy)-3 5-bis-trifluoromethyl-nhenylamine F
Reactants:
100 mg (0.206 mmol) of the nitro compound from Example XXVIII
100 mg of palladium/activated carbon (10%) in 10 ml of ethanol 3 bar, hydrogen Yield: 38.8 mg (39.6%) MS (ESI): 455 ([M+H]+, 100%) 200 MHz IH-NMR (CDCl3): 4.07 (broad s, 2H); 6.78 (dd, 1H); 7.04 - 7.16 (m, 5H);
7.25 - 7.31 (m, 2H); 7.45 - 7.51 (m, 2H); 8.12 (broad s, 1H).
Example XXXIX
4-(3-Methyl-1H-indol-5-yloxy)-3 5-bis-trifluoromethyl-nhenylamine Reactants:
0.55 g (1.37 mmol) of the nitro compound from Example XXIX
350 mg of palladium/activated carbon (10%) in 100 ml of methanol 3 bar, hydrogen Yield: 0.341 g {66.4%) MS (ES): 374 ([M]+, 100%) Rf = 0.69 (toluene : ethyl acetate = 1:1 ) Le A 34 254-Foreign Countries Example XL
4-f (3-Methoxy-carbonylmethyl)-1H-indol-5-yloxyl-3.5-bis-trifluoromethyl-phen 1y amine Hz H
Reactants:
0.55 g (1.05 mmol) of the nitro compound from Example XXX
50 mg of palladium/activated carbon (I0%) in 20 m1 of methanol 3 bar, hydrogen Yield: 0.436 g (94.8%) MS (ESI): 433 ([M+H]+, 15%) 300 MHz 'H-NMR (CDCI3): 3.62 (s, 3H); 3.67 (s, 2H); 4.0 (s, 2H); 6.79 (m, 2H);
7.13 (s, 3H); 7.22 (d, 1H); 7.95 (broad s, 1H).
Example XLI
Methyl (DL)-2-acetylamino-3-(5-(4-amino-2,6-bis-trifluoromethylphenoxy)-1H-indol-3=yll-propionate O

\ 'NH
~''(O
Reactants:
250 mg (0.41 mmol) of the nitro compound from Example XX~~I
120 mg of palladium/activated carbon (10%) in 100 ml of methanol 3 bar, hydrogen Yield: 228.6 mg (94.4%) MS (DCI): 521 ([M+NH~]+, 100%) Le A 34 254-Foreign Countries - 72 _ Rf = 0.1 (toluene : ethyl acetate = 1:2) HPLC rt = 4.8 (84.7%) 0.5% HC10~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Examule XLII
Methyl (DL)-2-acetylamino-3-f5-(4-amino-2,6-dibromophenoxy)-1H-indol-3-yll-propionate C
1.764 g (7.817 mmol) of tin-(II) chloride dihydrate are added to a solution of 0.868 g (1.563 mmol) of the vitro compound from Example XXXII in 16 ml of dimethylformamide and 1.6 ml of water, and the mixture is stirred at 50°C for 2 hours. The reaction solution is then admixed with 50 ml of saturated sodium bicarbonate solution and 50 ml of ammonium chloride solution and extracted four times with ethyl acetate. The organic phases are combined, filtered and concentrated under reduced pressure. The residue is purified by silica gel chromatography using toluene/ethyl acetate (20:1).
Yield: 0.697 g (84.9%) MS (LC method, ES+): 526 ([M+H]+, 100%) R f = 0.81 (toluene : ethyl acetate = 9:1 ) Example XLIII
3-Cyclobutanecarbonyl-S-(4-vitro-2,6-bis-trifluorometh-ylphenoxv)-1H-indole Le A 34 254-Forei~.n Countries Under argon, 380 mg (2.8 mmol) of zinc chloride and 0.47 ml (1.43 mmol) of ethylmagnesium bromide (3 molar in ether) are added to 550 mg (1.4 mmol) of the compound from Example I dissolved in 7 ml of dichloromethane. The mixture is stirred at room temperature for 1 hour, 0.2 ml (1.77 mmol) of cyclobutanecarbonyl chloride are then added, and the mixture is stirred at room temperature for 1 hour.
80 mg (0.61 mmol) of aluminium chloride are added, and the reaction solution is then stirred at room temperature overnight. The mixture is then diluted with dichloromethane and 1 ml of saturated ammonium chloride solution and 10 ml of water are added. The organic phase is separated, washed with sodium bicarbonate solution and sodium chloride solution, dried over sodium sulphate, filtered and concentrated. The crude product is purified by silica gel chromatography using toluene/ethyl acetate (9:1).
Yield: 283.8 mg (32.2%) MS (ESI)): 473 ([M+H]+, 100%) R~ = 0.24 (toluene : ethyl acetate = 2: I ) Example XLIV
4-(3-Cyclobutylmethyl-1H-indol-5-foxy)-3,5-bis-trifluoromethyl-phen~lamine Similarly to the procedure of Example XXX1SI, 150 mg (0.24 mmol) of the nitro compound from Example XLIII are hydrogenated in an atmosphere of hydrogen at 3 bar for 8 days, using 150 mg of palladium/activated carbon (10%).
Yield: 69.2 mg (63%) MS (ESI): 429 ([M+H]+, 100°!0) HPLC 1t = 5.04 (93. I %) 0.5% HC10~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Le A 34 254-Foreign Countries Example XLV
5-(2,6-Dibromo-4-nitrophenoxy)-1H-indole Br O
N~ / +~O-.
Br N
O
8.00 g (26.77 mmol) of 1,3-dibromo-2-fluoro-5-nitrobenzene are dissolved in 100 ml of DMSO. At room temperature, 4.069 g (29.44 mmol) of potassium carbonate and 3.674 g (26.77 mmol) of 5-hydroxyindole are added. The reaction mixture is stirred at room temperature for 3 h and then mixed with 50 ml of sat. ammonium chloride solution, the phases are separated and the aqueous phase is extracted twice with ethyl acetate. The combined organic extracts are washed once with sat. sodium chloride solution and dried over sodium sulphate, and the solvent is removed under reduced pressure. The residue is triturated (cyclohexane/diethyl ether/dichloromethane 3:3:1), giving 7.9 g (72%) of 5-(2,6-dibromo-4-nitrophenoxy)-1H-indole as a yellow solid.
300 MHz ~H-NMR (DMSO): 6.31, m, 1H; 6.79, m, 2H; 7.37, m, 1H; 7.39, d, 1H;
8.63, s, 2H; 11.12, s, broad, 1 H.
Example XLVI
3-C cly ohexylcarbon~-5-(2,6=dibromo-4-nitrophenoxy)-1H-indole +/O _ Le A 34 254-Foreign Countries At 0°C, a solution of 178 mg (1.21 mmol) of cyclohexanecarbonyl chloride in 5 ml of dichloromethane is added dropwise to a suspension of 324 mg (2.43 mmol) of aluminium trichloride in 10 ml of dichloromethane. The mixture is stirred at room temperature for 1 h, and, at 0°C, a solution of 500 mg (1.21 mmol) of 5-(2,6-dibromo-4-nitrophenoxy)-1H-indole in 8 ml of dichloromethane is then added dropwise. The reaction mixture is stirred at room temperature overnight and then heated at 50°C for 8 h, a further 178 mg (1.21 mmol) of cyclohexanecarbonyl chloride are added, and the mixture is heated at 50°C overnight. The mixture is then poured onto ice/2N hydrochloric acid, the aqueous phase is extracted 2x with dichloromethane and the combined organic extracts are dried over sodium sulphate.
The solvent is removed under reduced pressure and the residue is triturated with diethyl ether, giving 441 mg (70%) of 3-cyclohexylcarbonyl-5-(2,6-dibromo-4-nitrophenoxy)-1H-indole.
200 MHz 'H-NMR (DMSO): 1.37, m, SH; 1.71, m, SH; 3.12, m, 1H; 6.95, dd, 1H;
7.44, dd, 1H; 7.47, d, 1H; 8.38, d, 1H; 8.67, s, 2H; 12.00, d, broad, 1H.
Example XLVII
5-(2 6-Dibromo-4-nitrophenoxy)-3-isopropylcarbonyl-1H-indole +.O
N
I I
O
In a similar manner, 500 mg (1.21 mmol) of 5-(2,6-dibromo-4-nitrophenoxy)-1H-indole, 129 mg (1.21 mmol) of isobutyryl chloride and 324 mg (2.43 mmol) of aluminium trichloride give, after trituration of the crude product with diisopropyl ether/dichloromethane 5:1, 276 mg (47%) of 3-isopropylcarbonyl-5-(2,6-dibromo-nitrophenoxy)-1H-indole.

Le A 34 254-Foreign Countries 300 MHz'H-NMR (DMSO): 1.07, d, 6H; 3.40, sept, 1H; 6.97, dd, 1H; 7.46, dd, 1H;
7.49, d, 1H; 8.39, d, 1H; 8.67, s, 2H; 12.01, d, broad, 1H.
Examine XLVIII
3-(N-Benzyl-N-isopropyl-aminomethyl)-5-(2,6-dibromo-4-nitrophenoxy)-1H-indole / \
+.O_ N
O
At room temperature, 63 ~tl (0.80 mmol) of a 35% strength formaldehyde solution are added to a solution of 300 mg (0.73 mmol) of 5-(2,6-dibromo-4-nitrophenoxy)-1H-indole and 119.5 mg (0.80 mmol) of N-benzyl-N-isopropylamine in 2 ml of 1,4-dioxane and 0.4 ml of acetic acid. The mixture is stirred for 45 min and then admixed with water and adjusted to pH 11 using potassium carbonate. The aqueous phase is extracted 2x with dichloromethane and the combined organic extracts are dried over sodium sulphate and freed from the solvent under reduced pressure. The residue is purified on silica gel 60 (cyclohexane/ethyl acetate 10:1 - 2:1), giving 286 mg (69%) of 3-(N-benzyl-N-isopropyl-aminomethyl)-5-(2,6-dibromo-4-nitrophenoxy)-1H-indole.
200 MHz 'H-NMR (DMSO): 0.88, d, 6H; 2.74, sept, 1H; 3.40, s, 2H; 3.50, s, 2H;
6.88, s, 1H; 6.91, dd, 1H; 7.16, m, 6H; 7.34, d, 1H; 8.72, s, 2H; 10.85, d, broad, 1H.

1x A 34 254-Foreign Countries _77_ Example IL
3-(N-Benz 1-~N-ethxl-aminomethyl)-5-(2,6-dibromo-4-nitrophenoxy)-1H-indole NJ
Br O
N ~ / ~ /
H Br II
+.O _ O
In a similar manner, reaction of 350 mg (0.85 mmol) of 5-(2,6-dibromo-4-nitrophenoxy)-1H-indole with 126.3 mg (0.93 mmol) of N-benzyl-N-ethylamine and 74 p.1 (0.93 mmol) of 35% strength formaldehyde solution in 2 ml of 1,4-dioxane and 0.4 ml of acetic acid gives 272 mg (57°l0) of 3-(N-benzyl-N-ethylaminomethyl)-5-(2,6-dibromo-4-nitrophenoxy)-1H-indole.
200 MHz ~H-NMR (DMSO): 0.88, t, 3H; 2.30, q, 2H; 3.40, s, 2H; 3.52, s, 2H;
6.86, dd, 1H; 6.89, s, 1H; 7.20, m, 6H; 7.33, d, 1H; 8.71, s, 2H; 10.92, d, broad, 1H.
Example L
5-(4-Amino-2,6-dibromophenoxy)-1H-indole Br O
N ~ / /
H Br NH2 3.25 g (7.89 mmol) of 5-(2,6-dibromo-4-nitrophenoxy)-1H-indole are dissolved in 35 ml of DMF and 8 ml of water. At room temperature, a solution of 8.90 g (39.44 mmol) of tin(II) chloride dihydrate in 8 ml of conc. HC1 is added dropwise to Le A 34 254-Forei~ Countries _ 7g _ the solution, the temperature of the reaction solution increasing to 50°C. After the addition has ended, the mixture is stirred for a further 4 h and then adjusted to pH 12 using 45% strength aqueous sodium hydroxide solution and admixed with 10 ml of water, and the aqueous phase is extracted three times with ethyl acetate. The combined organic extracts are dried over sodium sulphate and the solvent is removed under reduced pressure. The resulting residue is crystallized from diethyl ether, and the mother liquor is purified once again chromatographically (silica gel 60, cyclohexane/ethyl acetate 3:1). This gives a total of 2.53 g (84%) of 5-(4-amino-2,6-dibromophenoxy)-1H-indole as a white solid.
300 MHz ~H-NMR (DMSO): 5.57, s, broad, 2H; 6.30, m, 1H; 6.68, m, 1H; 6.70, dd, 1H; 6.90, s, 2H; 7.30, m, 2H; 10.98, s, broad, 1H.
Example LI
5-(4-Amino-2,6-dibromophenoxy)-3-cyclohexylcarbonyl-1H-indole n NH2 At 50°C, a solution of 600 mg (3.447 mmol) of sodium dithionite in 15 ml of water is added dropwise to a solution of 300 mg (0.575 mmol) of 3-cyclohexylcarbonyl-(2,6-dibromo-4-nitrophenoxy)-1H-indole in 25 ml of ethanol. After the addition has ended, the mixture is heated at reflux for 3 h, admixed with another 200 mg (1.15 mmol) of sodium dithionite in 5 ml of water and heated at reflux overnight.
After cooling, the solid residues are filtered off, the filtrate is concentrated under reduced pressure and the residue is taken up in dichloromethane and a little methanol.
The organic phase is washed lx with sat. NaHC03 solution, the aqueous phase is extracted 2x with dichloromethane and the combined organic extracts are dried over sodium sulphate and concentrated under reduced pressure. Purification of the crude Le A 34 254-Foreign Countries product on silica gel 60 (cyclohexane/ethyl acetate 5:2) gives 70 mg (25%) of 5-(4-amino-2,6-dibromophenoxy)-3-cyclohexylcarbonyl-1H-indole.
200 MHz'H-NMR (DMSO): 1.35, m, SH; 1.72, m, 5H; 3.13, m, 1H; 5.10, s, broad, 2H; 6.87, dd, 1H; 6.90, s, 2H; 7.36, d, 1H; 7.39, d, 1H; 8.31, s, 1H; 11.89, s, broad, 1 H.
Example LII
5-(4-Ami no-2,6-di bromophenoxy)-3-i sopropylcarbonyl-1 H-indole 646 mg (2.86 mmol) of tin(II) chloride dihydrate are added to a solution of 276 mg (0.572 mmol) of 5-(2,6-dibromo-4-nitrophenoxy)-3-isopropylcarbonyl-1H-indole in 30 ml of DMF/water (5:1), and the reaction mixture is stirred at 50°C
for 2 h. The mixture is then poured into sat. NaHC03 solution, the aqueous phase is extracted 3x with ethyl acetate and the combined organic extracts are dried over sodium sulphate.
The solvent is removed under reduced pressure and the residue is then purified on silica gel 60 (cyclohexane/ethyl acetate 5:2), giving 142 mg (55%) of 5-(4-amino-2,6-dibromophenoxy)-3-isopropylcarbonyl-1H-indole.
400 MHz 'H-NMR (DMSO): 1.08, d, 6H; 3.39, sept, 1H; 5.58, s, broad, 2H; 6.87, dd, 1H; 6.92, s, 2H; 7.40, m, 2H; 8.30, d, 1H; 11.87, d, broad, 1H.

Le A 34 254-Foreign Countries Example LIII
5-(4-Amino-2,6-dibromophenoxy)-3-(N-benzyl-N-isopropylaminomethyl)-1H-indole / \
h H2 Similarly, reaction of 285 mg (0.497 mmol) of 3-(N-benzyl-N-isopropyl aminomethyl)-5-(2,6-dibromo-4-nitrophenoxy)-1H-indole with 561 mg (2.49 mmol) of tin(II) chloride dihydrate in 1.8 ml of DMF and 0.2 ml of water gives, after 3 h at 50°C and work-up with sat. NaHC03 solution, 148 mg (55%) of 5-(4-amino-2,6 dibromophenoxy)- 3-(N-benzyl-N-isopropyl-aminomethyl)-1H-indole.
300 MHz ~H-NMR (DMSO): 0.91, d, 6H; 2.77, sept, 1H; 3.42, s, 2H; 3.48, s, 2H;
5.54, s, broad, 2H; 6.80, dd, 1H; 6.96, d, 1H; 6.97, s, 2H; 7.20, m, 7H;
10.69, d, broad, 1H.
Example LIV
5-(4-Amino-2,6-dibromophenoxy)-3-(N-benzyl-N-ethyl-aminomethyl)-1H-indole / ~ /
HZ

Le A 34 254-Foreign Countries Similarly, reaction of 250 mg (0.447 mmol) of 3-(N-benzyl-N-ethylaminomethyl)-(2,6-dibromo-4-nitrophenoxy)-1H-indole with 504 mg (2.24 mmol) of tin(II) chloride dehydrate in 1.8 ml of DMF and 0.2 ml of water gives, after 2'/i h at 50°C
and work-up with sat. NaHC03 solution, 205 mg (86°70) of 5-(4-amino-2,6-dibromo phenoxy)-3-(N-benzyl-N ethyl-aminomethyl)-IH-indole.
200 MHz 'H-NMR (DMSO): 0.92, t, 3H; 2.29, q, 2H; 3.40, s, 2H; 3.49, s, 2H;
5.57, s, broad, 2H; 6.78, dd, 1H; 6.94, d, IH; 6.97, s, 2H; 7.22, m, 7H; 10.78, d, broad, 1H.
I0 Example LV
4-Benzylox~phenylhydrazine h~rochloride CI \ O \
NH3+~ ~ /
N
H
40 g (0.2mo1) of 4-benzyloxyaniline are suspended in 400m1 of water and, at 0°C, admixed with 1600 ml of conc. HCI. 16.6 g (0.24 mol) of sodium nitrite, dissolved in 100 ml of water, are added dropwise. The mixture is stirred vigorously at 0-5°C for 3 h. The dark solution is cooled to-10°C and carefully admixed dropwise with I13 g (0.5 mol) of tin chloride dehydrate in 50 ml of conc. HCI. The mixture is stirred at this temperature for one hour and the violet solid is filtered off with suction, washed with ether and dried under reduced pressure. The product (51.6 g) is used without further purification.
Example LVI
5-Benzyloxy-3-isopropylindole Le A 34 254-Foreign Countries 51.6 g (0.2 mol) of 4-benzyloxyphenylhydrazine hydrochloride in 800 ml of methanol are, together with 2 drops of conc. sulphuric acid and 17.7 g (0.2 mol) of 3-methylbutyraldehyde, heated at reflux for 3 hours. The solvent is removed under reduced pressure and the residue is digested with ethyl acetate. The organic solution is washed with sat. NaHC03 solution and sat. NaCI solution and dried, and the solvent is removed under reduced pressure. Chromatography (cyclohexane/ethyl acetate=20: to 10:1) gives 38.5 g (57%, 81% purity) of S-benzyloxy-3-isopropylindole.
300 MHz 'H-NMR (CDC13): 1.32, d, 6H; 3.13, kept, 1H; S.I 1, s, 2H; 6.91, m, 2H;
7.35, m, 7H; 7.76, s, broad, 1H.
Example LVII
5-Benzylox~3-hex~indole O
N
In a similar manner, 1 g (4 mmol) of 4-benzyloxyphenylhydrazine hydrochloride and 511 mg (4 mmol) of octanal give 1.21 g (81 %, 82% purity) of 5-benzyloxy-3-hexylindole. The product is used without further purification.

Le A 34 254-Foreign Countries Example LVIII
5-Benzyloxy-3-cyclohexylmethylindole H
In a similar manner, 1.5 g (6 mmol) of 4-benzyloxyphenylhydrazine hydrochloride and 839 mg (6 mmol) of 3-cyclohexylpropionaldehyde give 1.45 g (76%) of 5-benzyloxy-3-hexylindole.
300 MHz 'H-NMR (CDC13): 1.29, m, 6H; 1.65, m, 5H; 2.56, d, 2H; 5.11, s, 2H;
6.93, m, 2H; 7.37, m, 7H; 7.81, s, broad, 1H.
Example LIX
5-Benzyloxy-3-pentylindole H
In a similar manner, 1.5 g (6 mmol) of 4-benzyloxyphenylhydrazine hydrochloride and 683 mg (6 mmol) of heptanal give 1.58 g (crude yield) of 5-benzyloxy-3-pentylindole.
300 MHz 'H-NMR (CDC13): 0.95, m, 3H; 1.30, m, 2H; 1.55, m, 4H; 2.69, t, 2H;
5.11, s, 2H; 6.93, m, 2H; 7.38, m, 7H; 7.79, s, broad, 1H.

Le A 34 254-Foreign Countries Example LX
5-Benzylox~3-butylindole In a similar manner, 1.5 g (6 mmol) of 4-benzyloxyphenylhydrazine hydrochloride and 599 mg (6 mmol} of hexanal give 1.36 g (crude yield) of 5-benzyloxy-3-butylindole. The product is used without further purification.
Example LXI
5-Benzyloxy-3-propylindole In a similar manner, 5 g (19.9 mmol) of 4-benzyloxyphenylhydrazine hydrochloride and 1.72 g ( 19.9 mmol) of pentanal give 1.1 g (20%) of 5-benzyloxy-3-propylindole.
300 MHz 'H-NMR (CDCl3): 1.00, t, 3H; 1.71, m, 2H; 2.69, t, 2H; 5.12, s, 2H;
6.95, m, 2H; 7.35, m, 7H; 7.80, s, broad, 1H.

Le A 34 254-Foreign Countries Example LXII
S-Hydrox -y 3-hex lyndole OH
H
S
1.39 g (3.63 mmol) of S-Benzyloxy-3-hexylindole are dissolved in SO ml of methanol and hydrogenated overnight at atmospheric pressure, using I40 mg of Pd on carbon (10%).The reaction mixture is filtered through Celite, the solvent is removed under reduced pressure and the residue is purified by chromatography (cyclohexane/ethyl acetate = 10:1). This gives 223 mg (27%) of S-hydroxy-3-hexylindole.
300 MHz 'H-NMR (CDC13): 0.89, m, SH; 1.29, m, 4H; I.68> m, 2H; 2.67, t, ZH;
4.42, s, IH; 6.75, dd, IH; 6.95, m, 2H; 7.20, d, 1H; 7.77, s, broad, IH.
1 S Example LXIII
S-H,ydro~-3-cyclohexylmethylindole H
In a similar manner, 1.45 g (4.54 mmol) of S-Benzyloxy-3-cyclohexylmethylindole give 344 mg (32%) of S-hydroxy-3-cyclohexylmethylindole.

Ix A 34 254-Foreign Countries 300 MHz 'H-NMR (CDC13): 0.96, m, 5H; 1.19, m, 4H; 1.71, m, H; 2.56, d, 2H;
4.40, s, IH; 6.72, dd, IH; 6.96, dd, 1H; 7.21, d, 1H; 7.77, s, broad, 1H.
Examine LXIV
5-H,ydroxy-3-pent liy ndole In a similar manner, using 1.57 g (5.35 mmol) of 5-benzyloxy-3-pentylindole in a mixture of 20 ml of methanol and 10 ml of ether, 241 mg (19%) of 5-hydroxy-3-IO pentylindole are obtained.
300 MHz 'H-NMR (CDC13): 0.90, m, SH; 1.36, m, 2H; 1.68, m, 2H; 2.68, t, 2H;
4.48, s, I H; 6.75, dd, 1 H; 6.98, dd, 1 H; 7.20, d, 1 H; 7.75, s, broad, 1 H.
Example LXV
5-Hydroxy-3-butylindole OH
In a similar manner, using 1.35 g (4.83 mmol) of 5-benzyloxy-3-butylindole in a mixture of 20 ml of methanol and 20 ml of ether, 273 mg (19%) of 5-hydroxy-3-butylylindole are obtained.

Le A 34 254-Foreign Countries _87_ 300 MHz rH-NMR (CDC13): 0.93, t, 3H; 1.41, m, 2H; 1.68, m, 2H; 2.68, t, 2H;
4.43, s, 1 H; 6.?5, dd, 1 H; 6.97, dd, 1 H; 7.20, d, 1 H; 7.75, s, broad, 1 H.
Example LXVI
5-Hydroxy-3-propylindole In a similar manner, 1.08 g (4.07 mmol) of 5-benzyloxy-3-propylindole give 565 mg (79%) of 5-hydroxy-3-propylindole.
300 MHz 'H-NMR (CDCI3): 0.99, t, 3H; 1.70, sext, 2H; 2.65, t, 2H; 4.42, s, 1H;
6.75, dd, 1H; 6.99, dd, 1H; 7.20, d, 1H; 7.77, s, broad, 1H.
Example LXVII
5-(2,6-Dimethyl-4-nitrophenoxy)-3-3-propel-1 H-indole N+,O
H ~_ 116 mg (0.66 mmol) of 5-hydroxy-3-propylindole are dissolved in 4 ml of DMSO.
At room temperature, 100 mg (0.73 mmol) of potassium carbonate and 112 mg (0.66 mmol) of 2-fluoro-1,3-dimethyl-5-nitrobenzene are added. The reaction mixture is stirred at room temperature for 3 h and then at 1 IO°C for 2 h. The reaction mixture is poured into saturated ammonium chloride solution and extracted 3x with EA, and the combined organic phases are washed 3x with sat. NaCI solution, dried and concentrated using a rotary evaporator. The residue is purified Le A 34 254-Foreign Countries _88_ chromatographically (cyclohexane/ethyl acetate = 10:1). This gives 173 mg (78%) of 5-(2,6-dimethyl-4-nitrophenoxy)-3-propyl-1H-indole.
300 MHz 'H-NMR (CDC13): 0.91, t, 3H; 1.70, sext, 2H; 2.27, s, 6H; 2.58, t, 2H;
6.77, m, 2H; 6.90, m, 1H; 7.26, dd, 1H; 7.87, s, broad, 1H; 8.02, s, 2H.
Examine LXVIII
5-14-Nitro-2.6-bis trifluoromethyl)phenoxyl-3-propel-1H-indole ~O
N+
~' ' I _ In a similar manner, 120 mg (0.68 mmol) of 5-hydroxy-3-propylindole, 104 mg (0.75 mmol) of potassium carbonate and 201 mg of 2-chloro-5-nitro-1,3-bis(trifluoromethyl)benzene give, at room temperature, 301 mg (98%) of 5-[4-nitro-2,6-bis(trifluoromethyl)phenoxy]-3-propyl-1H-indole.
300 MHz ~H-NMR (CDC13): 0.95, t, 3H; 1.64, sext, 2H; 2.59, t, 2H; 6.72, dd, 1H;
6.83, d, 1H; 7.00, d, 1H; 7.27, d, 1H; 7.90, s, broad, 1H; 8.82, s, 2H.

Le A 34 254-Foreign Countries Example LXIX
5-(2,6-Dibromo-4-nitrophenoxy)-3-propyl-1H-indole ~O
O
In a similar manner, 100 mg (0.57 mmol) of 5-hydroxy-3-propylindole, 87 mg (0.63 mmol) of potassium carbonate and 171 mg (0.57 mmol) of 2-fluoro-5-nitro-1,3-dibromobenzene give 247 g (71%) of 5-(2,6-dibromo-4-nitrophenoxy)-3-propyl-1H-indole.
300 MHz ~H-NMR (CDCl3): 0.98, t, 3H; 1.68, sext, 2H; 2.62, t, 2H; 6.78, dd, 1H;
6.89, d, 1H; 7.01, m, IH; 7.29, dd, 1H; 7.92, s, broad, 1H; 8.52, s, 2H.
Example LXX
5-(2,6-Di bromo-4-ni trophenoxy)-3-methyl-1 H-i ndole ,O
H
O
In a similar manner, 1.26 g (8.56 mmol) of 5-hydroxy-3-methylindole, 1.3 g (9.4 mmol) of potassium carbonate and 2.56 g (8.56 mmol) of 2-fluoro-5-nitro-1,3-dibromobenzene give 2.81 g (75%) of 5-(2,6-dibromo-4-nitrophenoxy)-3-methyl-1H-indole.
300 MHz 1H-NMR (CDCI3): 2.23, s, 3H; 6.82, m, 2H; 7.00, m, 1H; 7.28, dd, 1H;
7.88, s, broad, 1H; 8.53, s, 2H.

Le A 34 254-Foreign Countries Example LXXI
3-Butyl-5-(2,6-dibromo-4-nitrophenoxy)-1H-indole +:O
O
In a similar manner, 130 mg (0.44 mmot) of 5-hydroxy-3-butylindole, 66 mg (0.48 mmol) of potassium carbonate and 131 mg (0.44 mmol) of 2-fluoro-5-nitro-1,3-dibromobenzene give 141 mg (66%) of 3-butyl-5-(2,6-dibromo-4-nitrophenoxy)-1H-indole.
300 MHz ~H-NMR (CDCl3): 0.93, t, 3H; 1.38, m, 2H; 1.63, m, 2H; 2.63, t, 2H;
6.77, dd, 1H; 6.90, d, 1H; 7.02, m, 1H; 7.28, d, 1H; 7.89, s, broad, 1H; 8.51, s, 2H.
Example LXXII
3-Butyl-5-14-vitro-2,6-bis(trifluoromethyl)phenox'yl-1H-indole N--~J

IS
In a similar manner, 130 mg (0.44 mmol, purity 64%) of 5-hydroxy-3-butylindole, 67 mg (0.48 mmol) of potassium carbonate and 129 mg (0.44 mmol) of 2-chloro-5-nitro-1,3-bis(trifluoromethyl)benzene give, at room temperature, 126 mg (57%) of 3-butyl-5-[4-vitro-2,6-bis(trifluoromethyl)phenoxy]-1H-indole.

Le A 34 254-Foreign Countries 300 MHz'H-NMR (CDC13): 0.90, t, 3H; 1.35, m, 2H; 1.60, m, 2H; 2.62, t, 2H;
6.71, dd, 1H; 6.83, d, 1H; 7.00, m, 1H; 7.24, d, 1H; 7.89, s, broad, 1H; 8.82, s, 2H.
Example LXXIII
5-f4-Nitro-2 6-bis(trifluorometh~phenoxyl-3-pentyl-1H-indole +, O
N
.. I
O
In a similar manner, 110 mg (0.54 mmol, purity 64%) of 5-hydroxy-3-pentylindole, 82 mg (0.59 mmol) of potassium carbonate and 159 mg (0.54 mmol) of 2-chloro-5-nitro-1,3-bis(trifluoromethyl)benzene give, at room temperature, 91 mg (34%) of 3-butyl-5-[4-nitro-2,6-bis(trifluoromethyl)phenoxy]-1H-indole.
300 MHz ~H-NMR (CDC13): 0.87, t, 3H; 1.31, m, 4H; 1.62, m, 2H; 2.61, t, 2H;
6.73, dd, 1H; 6.82, d, 1H; 7.00, m, 1H; 7.25, d, 1H; 7.91, s, broad, 1H; 8.82, s, 2H.
Example LXXIV
5-(2,6-Dibromo-4-nitrophenoxy)-3-pentyl-1 H-indole Br O
~O
3r N
I_ O

Le A 34 254-Foreign Countries In a similar manner, 110 mg (0.54 mmol) of 5-hydroxy-3-pentylindole, 82 mg (0.59 mmol) of potassium carbonate and 162 mg (0.54 mmol) of 2-fluoro-5-nitro-1,3-dibromobenzene give 72 mg (22%) of 5-(2,6-dibromo-4-nitrophenoxy)-3-pentyl-1H-indole.
300 MHz'H-NMR (CDC13): 0.88, t, 3H; 1.30, m, 4H; 1.65, m, 2H; 2.62, t, 2H;
6.77, dd, 1H; 6.88, d, 1H; 7.01, m, 1H; 7.29, d, 1H; 7.89, s, broad, 1H; 8.52, s, 2H.
Example LXXV
3-(Cyclohexylmethyl)-S-(4-vitro-2,6-bis(trifluoromethyl)phenoxy)-1H-indole +:~
In a similar manner, 170 mg (0.74 mmol) of 5-hydroxy-3-cyclohexylmethylindole, 113 mg (0.82 mmol) of potassium carbonate and 217 mg (0.74 mmol) of 2-chloro-5-vitro-1,3-bis(trifluoromethyl)benzene give, at room temperature, 319 mg (84%) of 3-(cyclohexylmethyl)-5-[4-vitro-2,6-bis(trifluoromethyl)phenoxyJ-1H-indole.
300 MHz 'H-NMR (CDCI3): 0.89, m, 2H; 1.19, m, 4H; 1.65, m, SH; 2.50, d, 2H;
6.71, dd, 1H; 6.83, d, 1H; 6.98, m, 1H; 7.23, d, 1H; 7.92, s, broad, 1H; 8.82, s, 2H.

Le A 34 254-Foreign Countries Example LXXVI
3-(Cyclohexylmethyl)-5-(2.6-dibromo-4-nitrophenoxy)-1H-indole +:O
O
In a similar manner, 165 mg (0.72 mmol) of 5-hydroxy-3-cyclohexylmethylindole, 109 mg (0.79 mmol) of potassium carbonate and 215 mg (0.72 mmol) of 2-fluoro-5-nitro-1,3-dibromobenzene give 281 mg (69%) of 3-(cyclohexylmethyl)-5-(2,6-dibromo-4-nitrophenoxy)-1H-indole.
300 MHz 'H-NMR (CDC13): 0.92, m, 2H; 1.18, m, 4H; 1.65, m, 5H; 2.52, d, 2H;
6.75, dd, 1 H; 6.91, d, 1 H; 7.25, d, 1 H; 7.91, s, broad, 1 H; 8.51, s, 2H.
Example LXXVII
3-Hexyl-5-(4-nitro-2,6-bis(trifluorometh~phenoxyl-1 H-indole \ O ~ \
H~F C ~ N+~O

O
In a similar manner, 97 mg (0.45 mmol) of 5-hydroxy-3-hexylindole, 68 mg (0.49 mmol) of potassium carbonate and 131 mg (0.45 mmol) of 2-chloro-5-nitro-1,3-bis(trifluoromethyl)benzene give, at room temperature, 121 mg (57%) of 3-hexyl-5-[4-nitro-2,6-bis(trifluoromethyl)phenoxy)-1H-indole.

Le A 34 254-Foreign Countries 300 MHz ~H-NMR (CDC13): 0.89, m, SH; 1.25, m, 4H; 1.62, m, 2H; 2.60, t, 2H;
6.73, dd, 1 H; 6.84, d, 1 H; 7.00, m, 1 H; 7.25, d, 1 H; 7.90, s, broad, 1 H;
8.82, s, 2H.
Example LXXVIII
5-(2,6-Dibromo-4-nitrophenoxy)-3-hexyl-1H-indole In a similar manner, 97 mg (0.45 mmol) of 5-hydroxy-3-hexylindole, 68 mg (0.49 mmol) of potassium carbonate and 133 mg (0.45 mmol) of 2-fluoro-5-nitro-1,3-dibromobenzene give 108 mg (49%) of 5-(2,6-dibromo-4-nitrophenoxy)-3-hexyl-1H-indole.
300 MHz ~H-NMR (CDC13): 0.88, m, SH; 1.29, m, 4H; 1.65, m, 2H; 2.62, t, 2H;
6.79, dd, 1H; 6.89, d, 1H; 7.00, m, 1H; 7.28, d, 1H; 7.90, s, broad, 1H; 8.52, s, 2H.
Example LXXIX
~ S-f4-Nitro-2,6-bis(trifluoromethyl)phenoxyl-1H-indol-3-y~phenyl)methanone .:~
200 mg (0.4 mmol) of 3-benzyl-5-[4-nitro-2,6-bis(trifluoromethyl)phenoxy]-1H-indole are dissolved in 3 ml of a mixture of THF/water (10:1) and, at room Le A 34 254-Foreign Countries temperature, admixed dropwise with a solution of 182 mg (0.8 mmol) of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in 2 ml of THF. The mixture is stirred at room temperature for 1 h, the solvent is removed under reduced pressure and the residue is stirred with dichloromethane. The mixture is filtered off with suction and the solid is dried. This gives 165 mg (80%) of {5-[4-nitro-2,6-bis(trifluoromethyl)phenoxy]-1H-indol-3-yl } (phenyl)methanone.
300 MHz 'H-NMR (CDCI3): 7.03, m, 1H; 7.13, m, 2H; 7.42, d, 1H; 7.52, d, 1H;
7.69, d, 1H; 7.80, dd, 2H; 8.68, s, broad, 1H; 8.83, s, 2H.
Example LXXX
3 5-Dibromo-4-f(3-hexyl-1H-indol-5- l~ylaniline n NHZ
102 mg (0.21 mmol) of 5-(2,6-dibromo-4-nitrophenoxy)-3-hexyl-1H-indole are dissolved in a solution of 278 mg (1.2 mmol) of tin chloride dehydrate in 2 ml of conc. HC1, and the solution is heated at 70°C for 60 min. After cooling, the mixture is poured into water, made alkaline using 1N NaOH and extracted 3 times with ether.
The combined organic phases are dried and the solvent is removed under reduced pressure. This gives 68 mg (51%; 72% purity) of 3,5-dibromo-4-[(3-hexyl-1H-indol-5-yl)oxy]aniline which is used without further purification.
300 MHz 'H-NMR (CDCI3): 0.98, m, SH; 1.29, m, 4H; 1.65, m, 2H; 2.62, t, 2H;
3.71, s, broad, 2H; 6.80, m, 1H; 6.92, m, 3H; 7.23, d, 1H; 7.80, s, broad, 1H.

Le A 34 254-Foreign Countries Example LXXXI
3.5-Dibromo-4-1 f3-(cyclohexylmethyl)-1H-indol-5-ylloxylaniline HZ
In a similar manner, 265 mg (0.52 mmol) of 3-(cyclohexylmethyl)-5-(2,6-dibromo-nitrophenoxy)-1H-indole and 706 mg (3.13 mmol) of tin chloride dehydrate give, with addition of ethanol, 193 mg (53%) of 3,5-dibromo-4-{ [3-(cyclohexylmethyl)-1H-indol-5-yl]oxy}aniline.
300 MHz 'H-NMR (CDCl3): 0.90, m; 1.88, m; 1.68, m; 2.52, d, 2H; 3.7I, s, broad, 2H; 6.78, dd, 1H; 6.92, m, 3H; 7.22, d, 1H; 7.80, s, broad, 1H.
Example LXXXII
4-( (3-(Cyclohexylmethyl)-1H-indol-5-ylloxy~-3,5-bis(trifluoromethyl)aniline At atmospheric pressure, 300 mg (0.62 mmol) of 3-(cyclohexylmethyl)-5-[4-nitro-2,6-bis(trif7uoromethyl)phenoxy]-1H-indole in 30 ml of methanol are hydrogenated overnight using 30 mg of palladium on carbon (10%). The mixture is filtered through kieselguhr and the solvent is removed under reduced pressure. This gives 258 mg (66%) of 4-{[3-(cyclohexylmethyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoromethyl)-aniline.

L.e A 34 254-Foreign Countries 300 MHz 'H-NMR (CDCl3): 0.92, m; 1.13, m; 1.67, m; 2.50, d, 2H; 3.99, s, broad, 2H; 6.71, dd, 1 H; 6.90, m, 1 H; 7.16, s, 2H; 7.70, d, 1 H; 7. 80, s, broad, 1 H.
Example LXXXIII
3 5-Dibromo-4-f(3-pentyl-1H-indol-5- 1y )oxylaniline 65 mg (0.11 mmol) of 5-(2,6-dibromo-4-nitrophenoxy)-3-pentyl-1H-indole are dissolved in a solution of 146 mg (0.65 mmol) of tin chloride dihydrate in 2 ml of conc. HCI and 2 ml of ethanol, and the solution is heated at 70°C for 60 min. After cooling, the solution is poured into water, made alkaline using 1N Na~H and extracted 3 times with ether. The combined organic phases are dried and the solvent is removed under reduced pressure. Chromatographic purification (cyclohexane/ethyl acetate = 5:1) gives 35 mg (69%) of 3,5-dibromo-4-((3-pentyl-1H-indol-5-yl)oxy]aniline.
300 MHz IH-NMR (CDC13): 0.89, m; 1.32, m; I.68, m; 2.63, t, 2H; 3.70, s, broad, 2H; 6.80, dd, 1H; 6.93, m, 3H; 7.23, d, 1H; 7.80, s, broad, 1H.
Example LXXXIV
4-f(3-Pentyl-1H-indol-5- Iy )oxyl-3,5-bis~trifluorometh Iy )aniline Le A 34 254-Foreign Countries _98-At atmospheric pressure, 72 mg (0.16 mmol) of 5-[4-nitro-2,6-bis-(trifluoromethyl)phenoxyj-3-pentyl-IH-indole in 10 ml of methanol are hydrogenated overnight using 7 mg of palladium on carbon (10%). The mixture is filtered through kieselguhr and the solvent is removed under reduced pressure. Chromatography (cyclohexane/ethyl acetate = 5:1) gives 46 mg (66%) of 4-[(3-pentyl-1H-indol-5-yl)oxyj-3,5-bis(trifluoromethyl)aniline.
300 MHz ~H-NMR (CDCl3): 0.88, m, 5H; 1.29, m; 1.69, m; 2.60, t, 2H; 4.00, s, broad, ZH; 6.71, dd, 1H; 6.80, m, 1H; 6.92, m, 1H; 7.16, s, 2H; 7.20, d, 1H;
7.77, s, broad, IH.
Example LXXXV
3.5-Dibromo-4-f (3-butyl-1H-indol-5-yl)oxylaniline 119 mg (0.25 mmol) of 3-butyl-5-(2,6-dibromo-4-nitrophenoxy)-1H-indole in 4 ml of conc. HCI, 2 ml of ethanol and 2 ml of THF are heated with 343 mg (1.52 mmol) of tin chloride dihydrate at 70°C for 60 min. After cooling, the mixture is poured into water, made alkaline using 1N NaOH and extracted 3 times with ether. The combined organic phases are dried and the solvent is removed under reduced pressure. Chromatographic purification (cyclohexanelethyl acetate = 10:1) gives 78 mg (61%, 86% purity) of 3,5-dibromo-4-[(3-butyl-1H-indol-5-yl)oxyjaniline.
300 MHz ~H-NMR (CDCI3): 0.92, m; 1.38, m; 1.70, m; 2.63, t, 2H; 6.80, dd, 1H;
6.92, m, 4H; 7.22, d, 1H; 7.80, s, broad, 1H.

Le A 34 254-Foreign Countries Example LXXXVI
4-[(3-Butyl-1 H-indol-5-yl)oxyl-3.5-bis(trifluoromethyl)aniline At atmospheric pressure, 104 mg (0.23 mmol) of 3-butyl-5-[4-vitro-2,6-bis(trifluoromethyl)phenoxyJ-1H-indole in 10 ml of methanol are hydrogenated overnight using 10 mg of palladium on carbon (I0%). The mixture is filtered through kieselguhr and the solvent is removed under reduced pressure. Chromatography (cyclohexane/ethyl acetate = 10:1) gives 50 mg (49%) of 4-[(3-butyl-1H-indol-5-yl)oxyJ-3,5-bis(trifluoromethyl)aniline.
300 MHz ~H-NMR (CDC13): 0.91, t, 3H; 1.37, m, 2H; 1.62, m, 2H; 2.62, t, 2H;
3.98, s, broad, 2H; 6.71, dd, 1H; 6.81, d, 1H; 6.95, m, 1H; 7.28, s, 2H; 7.21, d, 1H; 7.79, s, broad, 1H.
Examine LXXXVII
4-[(3-Propyl-1H-indol-5-yl)oxY1-3,5-bis(trifluoromethyl)aniline At atmospheric pressure, 290 mg (0.67 mmol) of 5-[4-vitro-2,6-bis(trifluoromethyl)phenoxyJ-3-propyl-1H-indole in 30 ml of methanol are hydrogenated overnight using 30 mg of palladium on carbon (10%). The mixture is filtered through ltieselguhr and the solvent is removed under reduced pressure.

Le A 34 254-Forei ~n Countries Chromatography (cyclohexane/ethyl acetate = 5:1) gives 77 mg (28%) of 4-[(3-propyl-1H-indol-5-yl)oxy]-3,5-bis(trifluoromethyl)aniline.
300 MHz 'H-NMR (CDC13): 0,95, t, 3H; 1.66, sext, 2H; 2.61, t, 2H; 6.76, dd, 1H;
6.86, m, 1H; 6.98, m, 1H; 7.28, m; 7.86, s, broad, 1H.
Example LXXXVIII
3.5-Dibromo-4-f (3-propel-1H-indol-5-yl)oxylaniline Br \ O ~ \
H~ Br ~ NH2 240 mg (0.53 mmol) of 5-(2,6-dibromo-4-nitrophenoxy)-3-propyl-1H-indole are admixed with 716 mg (3.17 mmol) of tin chloride dihydrate dissolved in 8 ml of conc. HCI. Ethanol is added until a clear solution is obtained, and the mixture is heated at 70°C for 60 min. After cooling, the mixture is poured into water, made alkaline using 1N NaOH and extracted 3 times with ether. The combined organic phases are dried and the solvent is removed under reduced pressure.
Chromatographic purification (cyclohexane/ethyl acetate = 10:1) gives 215 mg (96%) of 3,5-dibromo-4-[(3-propyl-1H-indol-5-yl)oxy]aniline.
300 MHz 'H-NMR (CDC13): 0.97, t, 3H; 1.67, sext, 2H; 2.62, t, 2H; 3.71, s, broad, 2H; 6.79, dd, 1 H; 6.92, m, 4H; 7.23, d, 1 H; 7.81, s, broad, 1 H.

Le A 34 254-Foreign Countries t A
'101' Exemplary embodiments Example 1 Ethyl 2-f4-(1H-indol-S-vloxY)-3,5-bis(trifluorometh 1 anilin~2-oxoacetate O
H'~ F3C r N O~
H O
200 mg (0.56 mmol) of 4-(1H-indol-5-yloxy)-3,5-bis(trifluoromethyl)aniline and 1.05 g (7.22 mmol) of diethyl oxalate in 10 ml of toluene are heated at reflux overnight. The reaction mixture is diluted with water, the organic phase is dried over sodium sulphate and the solvent is removed under reduced pressure.
Chromatographic purification gives 158 mg (62%) of ethyl 2-[4-(1H-indol-5-yloxy)-3,5-bis-(trifluoromethyl)anilino]-2-oxoacetate.
200 MHz 1H-NMR (DMSO-d6): 1.3r, t, 3H: 4.36, quart, 2H; 6.30 s, 1H: 6.71, m, 2H; 7.30, m, 2H; 8.61, s, 2H; 11.05, s, IH; l I.42, s, 1H.
Example 2 Ethyl 2-f4-( 1H-indol-5-yloxy)-3,5-dimethylanilinol-2-oxoacetate O ~ ~ . O
H''~ / N O
I
H O
840 mg (3.33 mmol) of 4-(1H-indol-5-yloxy)-3,5-dimethylaniline and 6.32 g (43.3 mmol) of diethyl oxalate in 60 ml of toluene are heated at reflux overnight. The reaction mixture is subjected to chromatographic purification (toluene/ethyl acetate =
4:1). This gives 890 mg (76%) of ethyl 2-[4-(1H-indol-5-yloxy)-3,5-bis-dimethylanilino]-2-oxoacetate.

Le A 34 254-Foreign Countries 400 MHz 1H-NMR (DMSO-d6): I.33, t, 3H: 2.08, s, 6H; 4.31, quart, 2H; 6.26, m, 1H; 6.63, m, IH; 6.71, dd, 1H; 7.30, m, 2H; 7.51, s, 2H; 10.62, s, 1H; 10.95, s, 1H.
Example 3 Ethyl 2-13 5-dimethyl-4-[3-methyl-1H-indol-5-yl)oxyianilinol-2-oxoacetate 72 mg (0.72 mmol) of 3,5-dimethyt-4-[(3-methyl-1H-indol-5-yl)oxy]aniline and 513 mg (3.5 mmol) of ethyl oxalyl chloride in 5 mI of toluene are stirred at room temperature overnight. Chromatographic purification (toluene/ethyl acetate =

9:I -ethyl acetate) gives 97 mg (99%) of ethyl 2-{3,5-dimethyl-4-[(3-methyl-1H-indol-5-yl)oxy]anilino }-2-oxoacetate.
200 MHz 1H-NMR (DMSO-d6): 1.33, t, 3H: 2.08, s, 6H; 2.11, s, 3H: 4.31, quart, 2H; 6.62, s, 2H; 7.08> m, 1H; 7.25, dd, IH; 7.52, s, 2H; 10.66, s, IH; 10.70, s, 1H.
Example 4 Ethyl N-f4-(3-isopropyl-1H-indol-5-yloxy)-3..5-bis-trifluoromethyl-phenylloxamate ~ O ~ O

O
457 mg (1.14 mmol) of 4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenylaxnine are dissolved in 100 ml of dichIoromethane, admixed with 0.2 ml (1.43 mmol) of triethylamine and, under argon, reacted with 210 mg ( 1.53 mmol) of ethyl oxalyl chloride dissolved in 50 ml of dichloromethane, which is added at room temperature over a period of 1 hour. After 3 hours, the reaction is quenched by adding 100 ml of buffer solution (pH = 7.0), the dichloromethane layer is separated off and the aqueous layer is extracted Le A 34 254-Foreign Countries i three times with dichloromethane. The combined organic phases are dried over sodium sulphate and concentrated, whereupon a grey powder remains. The crude product is purified by chromatography on 200 ml of silica gel using toluene with added ethyl acetate in a gradient method (490 ml of toluene/IO ml of ethyl acetate to 400 ml of toluene/100 ml of ethyl acetate mixture).
Yield: 492.5 mg (81.4%) Rf: 0.36 (toluene:ethyl acetate = 9:1) HPLC: rC (%) = 5.16 (94.28) Example 5 Ethyl N-f4-(3-ethyl-1H-indol-5-yloxy~-3,5-bis-trifluoromethyl phenylloxamate O
H~F3C ~ H O
O
Similarly to the procedure of Example 4, 326.7 mg (0.84 mmol) of 4-(3-ethyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenylamine are reacted with 235.0 mg (1.72 mmol) of ethyl oxalyl chloride in the presence of 0.13 ml (0.93 mmol) of tri-ethylamine and 40 ml of dichloromethane. After 3 hours of stirring at room temperature, another 80 mg (0.59 mmol) of ethyl oxalyl chloride, dissolved in SO ml of dichloromethane, are added dropwise over a period of 15 minutes.
Following the addition of the acid chloride, the product is isolated and chromatographed according to the procedure of Example 4.
Yield: 345.6 mg (94.2%) Rf: 0.38 (toluene:ethyl acetate = 9:1) HPLC: rt (%) = 4.98 (94.2) 1% HC104/acetonitrile Le A 34 254-Foreign Countries Example 6 Ethyl ~ f4-~ f3-(4-fluorobenzyl)-1H-indol-5-ylloxy~-3,5-bis(trifluoromethyl)phenyll amino)(oxo) acetate F

O
H~F3C ~ H O
O
106 mg (0.12 mmol) of 4-{ [3-(4-fluorobenzyl)-1H-indol-5-yl]oxy}-3,5-bis(tri-fluoromethyl)aniline and 13 mg (0.13 mmol) of triethylamine are initially charged together in 1.3 ml of dichloromethane. 22 mg (0.16 mmol) of ethyl oxalyl chloride are added dropwise, and the mixture is stirred at room temperature for 3 h.
The reaction mixture is mixed with sat. NaHC03 solution, the phases are separated and the organic phase is washed once with saturated NaCI solution, dried and concentrated using a rotary evaporator. Chromatographic purification (toluene/acetonitrile) gives 33 mg (40%) of ethyl { [4-{ [3-(4-fiuorobenzyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoromethyl)phenyl]amino}(oxo) acetate.
300MHz 'H-NMR (CDC13): 1.48, t, 3H; 3.95, s, 2H; 4.48, quart, 2H; 6.42, d, 1H;
6.88, m, 4H; 7.12, m, 2H; 7.23, m, 1H; 7.90, s, broad, 1H; 8.21, s, 2H; 9.10, s, broad, 1 H.

Ix A 34 2S4-Foreign Countries Example 7 Ethyl f(3,5-dibromo-4-( f3-(4-fluorobenzyl)-1H-indol-5-ylloxy~,phenyl)aminol-(oxo)acetate O
N O
n H
O
50 mg (0.10 mmol) of 3,5-dibromo-4-{ [3-(4-fluorobenzyl)-1H-indol-5-yl]oxy}aniline and 11 mg (0.11 mmol) of triethylamine are initially charged together in 1.3 ml of dichloromethane. 19 mg (0.14 mmol) of ethyl oxalyl chloride are added dropwise, and the mixture is stirred at room temperature for 3 h. The reaction mixture is admixed with sat. NaHC03 solution, the phases are separated and the organic phase is washed lx with saturated NaCI solution, dried and concentrated using a rotary evaporator. Chromatographic purification (toluene/acetonitrile) gives 34 mg (57%) of product.
300MHz'H-NMR (CDC13): 1.45, t, 3H; 3.96, s, 2H; 4.45, quart, 2H; 6.57, d, 1H;
6.88, m, 4H; 7.17, m, 2H; 7.28, m, 1H; 7.90, s, broad, 1H; 7.95, s, 2H; 8.87, s, 1H.
Example 8 Ethyl (~4-f(3-isopropyl-1H-indol-5- 1)y meth,yll-3,5-dimethyl-phenyl-)amino)-(oxo acetate \ ~ \ O
N / / N O\/
H H
O

Le A 34 254-Foreign Countries 8 mg of 4-[(3-isopropyl-1H-indol-5-yl)methyl]-3,5-dimethylaniline (0.026 mmol) and 5 mg (0.035 mmol) of ethyl oxalyl chloride are initially charged in 1 ml of dichloromethane. 3 mg (0.029 mmol) of triethylamine, dissolved in 1 ml of dichloromethane, are added dropwise at 0°C over a period of about 20 min. The mixture is stirred at 0°C for 4 h and then diluted with dichloromethane and extracted with NaHC03 and NaCI solution. The organic phase is dried and concentrated using a rotary evaporator. Chromatography (cyclohexane/ethyl acetate=7:1) gives 10 mg of ethyl ({4-[(3-isopropyl-1H-indol-5-yl)methyl]-3>5-dimethyl-phenyl-)-amino)-(oxo)acetate.
RF (cyclohexane/ethyl acetate 3:1) = 0.35 Example 9 Eth~rl N-f4-(3-isopropyl-1H-indol-5-yloxy)-3,5-dibromo~henyl~~[_oxamate Br O
N'' U ~ ~ O
H
O
IS The preparation is carried out similarly to the procedure of Example 4 using 128.7 mg (0.3 mmol) of 4-(3-isopropyl-1H-indol-5-yloxy)-3,5-dibromophenylamine and 55.9 mg (0.41 mmol) of ethyl oxalyl chloride in the presence of 0.05 ml (0.36 mmol) of triethylamine. The crude product is precipitated from 20 ml of toluene by addition of cyclohexane, agitated in an ultrasonic bath, filtered off with suction, washed on the fitter with cyclohexane and dried under high vacuum.
Yield: 156.1 mg (97.6 °!o) RE: O.S3 (toluene : ethyl acetate = 8:2) MS (DCI): 525 ([M+H]+, 40%) NMR (300 MHz, CDC13): b=1.29 (d, 6H); 1.45 ~t, 3H); 3.09 (quip, 1H); 4.44 (quart, ZH); 6.78 (dd, IH); 6.96 (dd, 2H); 7.26 (d, 1H); 7.83 (s, 1H); 7.97 (s, 2H);
8.88 (s, 1 H) ppm.

Le A 34 254-Forei ~n Countries Examule 10 N-f4-(3-Isopropyl-1H-indol-5-yloxy)-3,5-dibromophenyll-oxamic acid / ~ ~ ~ O
Br ~ N OH
H I
O
Under argon, 35 mg (0.067 mmol) of the ethyl oxamate from Example 9 are dissolved in 2 ml of dioxane, and 0.9 ml of 1 molar aqueous sodium hydroxide solution are added dropwise. The reaction solution is stirred at room temperature for 6 hours and then admixed with 1 ml of 1 molar hydrochloric acid and 3 ml of NH4Cl solution with addition of 40 ml of ethyl acetate, the ethyl acetate layer is separated off and the aqueous phase is extracted two more times with ethyl acetate. The combined organic phases are dried over sodium sulphate and concentrated. The crude product is purified by silica gel chromatography using toluene/ethyl acetate (I:1) and ethyl acetate/methanol (1:1).
Yield: 21.3 mg (64.5%) MS (ES): 497 ([M+H]+, 100%) HPLC: rt (%) = 4.43 (100%) 0.01 M H3P0~/acetonitrile Kromasil column C18 (60 x 2 mm) Flow rate 0.75 ml/min, 210 nm.

Le A 34 254-Foreign Countries Example 11 N- f3 5-Dibromo-4-(3-isopropyl-1H-indol-5=yloxy)-phenyll-pyridine-2-carboxamide / ~ O
H
'~ Br \ H
N /
A solution of I 10 mg (0.26 mmol) of the phenylamine derivative from Example XVI
in IO ml of dichloromethane is admixed successively with 0.11 ml (0.79 mmol) of triethylamine and 60 mg (0.40 mmol) of picolinoyl chloride hydrochloride, with ice-cooling. Without cooling, the reaction solution is then stirred at room temperature for 3 hours, diluted with 60 ml of dichloromethane and washed with saturated NH4Cl solution. The mixture is dried over sodium sulphate, the solvent is removed and the residue is then purified by silica gel column chromatography using toluene and toluene and toluene/acetonitrile (25:1).
Yield: 115.2 mg (82.4%) Rf: 0.67 (toluene : acetonitrile = 4:1) MS (DCI): 545 ([M+NH.~]+, 52%) NMR (200 MHz, CDC13): b=1.3 (d, 6H); 3.19 (quin, 1H); 6.79 (d, 1H); 6.84 (d, 1H);
6.95-6.99 (dd, 2H); 7.27 (d, 1H); 7.48-7.55 (m, 1H); 7.81 (broad s, IH); 7.93 (m, 1H); 8.13 (s, 2H); 8.3 (d, 1H); 8.51 (m, 1H); 10.1 (s, 1H) ppm.

Le A 34 254-Foreign Countries Example 12 N~3 5-Dibromo-4-(3-isopropel-IH-indol-5-yloxy)-phenyll-hexanamide Br O
~/ \
H Br H
The preparation is carried out similarly to the procedure of Example 11 using 80 mg (0.19 mmol) of the phenylamine derivative from Example XVI, 30 mg (0.25 mmol) of n-hexanoyl chloride and 0.03 ml (0.21 mmol) of triethylamine in 10 ml of dichloromethane. The reaction solution is added to saturated NH:~CI and NaHC03 solution and extracted three times with ethyl acetate, the organic phases are dried over sodium sulphate and the solvent is distilled off under reduced pressure.
Yield: 80.9 mg (80.3%) R f : 0.35 (toluene : ethyl acetate = 9:1 ) MS (DCI): 538 ([M+NH.~]+, 68%) NMR (400 MHz, CDC13): b=0.91 (t, 3H); 1.29 (d, 6H); 1.37 (m, 4H); 1.73 (m, 2H);
2.37 (t, 2H); 3.08 (quin, 1H); 6.78 (dd, 1H); 6.95 (dd, 2H); 7.08 (s, 1H);
7.23 (d, 1H);
7.8 (s, 1H); 7.85 (s, 2H) ppm.

Le A 34 254-Forei~,n Countries Example 13 Ethyl N-f4-(3-isopropyl-1H-indol-5-yloxy)-3,5-divinylphenyll-oxamate O
O~-N
H
O
The preparation is carried out similarly to the procedure of Example 4 using 62.2 mg (0.2 mmol) of the indole derivative from Example XVIII and 36.0 mg (0.26 mmol) of ethyl oxalyl chloride in the presence of 0.03 ml (0.21 mmol) of triethylamine.
The product is crystallized using diisopropyl ether.
Yield: 57.1 mg (68.2%) Rf: 0.29 (toluene : ethyl acetate = 9:1) MS (ESI): 441 ([M+Na]+, 100%) 1S NMR (200 MHz> CDC1;): b=1.27 (d, 6H); 1.46 (t, 3H); 3.03 (quin, 1H); 4.45 (quart, 2H); 5.21 (d, 2H); 5.77 (d, 2H); b.72 (dd, 1H); 6.81 (d, 1H); 6.9 (dd, 2H);
7.21 (d, 1H); 7.79 (broad s, 1H); 7.85 (s, 2H); 8.9 (s, 1H) ppm.
Example I4 Ethyl N-f4-(3-isopropyl-1H-indol-5-~ )-y-3~5-dicyclo~ropylphenyll-oxamate O
N ~ N
H H
O

Le A 34 254-Foreign Countries Similarly to the procedure of Example 4, 40 mg (0.13 mmol) of the indole derivative from Example XV are reacted with 30 mg (0.I9 mmol) of ethyl oxalyl chloride in the presence of 0.02 ml (0.15 mmol) of triethylamine in 8 ml of dichloromethane.
Isolation and chromatography of the crude product give 8.1 mg (15.7%) of product.
MS (ESI): 496 ((M+Na]+, 96.8%) Rf: 0.58 (toluene:acetonitrile = 8:2) HPLC: rt (%) = 5.24 (96.8%) 0.01 M H3P04/acetonitrile Kromasil column C 18 (60 x 2 mm) Flow rate 0.75 ml/min, 210 nm.
Example 15 Ethyl N-~f3-(2-tent-butoxycarbonylaminoeth_yl)-1H-indol-5-yloxyl-3.5-bis-trifluoromethy~henyl -oxamate O ~ O

H ~, Fs N
H
O
Similarly to the procedure of Example 4, 254.3 mg (0.51 mmol) of the indole derivative from Example XXII are reacted with 93.1 mg (0.68 mmol) of ethyl oxalyl chloride in the presence of 0.08 ml (0.56 mmol) of triethylamine in 35 ml of dichloromethane for 2.5 hours. The crude product was purified on about 80 ml of silica gel using toluenelacetonitrile (isocratic, 9:1).
Yield: 331.7 mg ( 100%) MS (ESI): 604 ([M+H]+, 15%) Le A 34 254-Foreign Countries Rf : 0.38 (toluene:acetonitrile = 8:2) HPLC: rt (%) = 4.80 (94.3%) 1 % strength HCIO~/acetonitrile Kromasil column C18 (60 x 2 mm) Flow rate 0.75 ml/min, 210 nm.
The following examples are prepared similarly to the examples above:
Example Structure No.
16 ~H3 \ o i I o OH
H~H3C \ H
O

O
N
OH
O

CHI
\ O / ~ O
N~ \ O~CH3 H H'C H I' O
19 cH, H / HaC \ H O ~ \

Le A 34 254-Foreign Countries Example Structure No.

H3C/~O~N ~ \ F
IO' -O
F F F / N
H
21 H,c ",c'~'°~o H
H,c~O I \ F
O
_O
F F F / N
H
F

HOC -\ O ~ ~ H °
/ F
N
H F

NHz F O O
H
F
N
H F

F ~O~
\ ° i ~ ~ °
~ i/ F
H F F

F O-, .OH
\
F
N
H F

Le A 34 254-Foreign Countries Examule 26 Ethyl N-[4-(sec-butyl-1H-indol-5-yloxy)-3,5-dimethylphenyl]-oxamate O
O
1.52 g (4.93 mmol) of 4-(3-sec-butyl-IH-indol-5-yloxy)-3,5-dimethylphenyIamine are dissolved in 200 ml of dichloromethane, and 0.44 ml (5.43 mmol) of pyridine and then 0.75 ml (6.66 mmol) of ethyl oxalyl chloride are added dropwise with stirring, under argon and at room temperature.
After one hour of stirring at room temperature, the reaction solution is mixed with buffer of pH = 7, the organic phase is separated off and the aqueous phase is extracted twice with dichloromethane. The combined organic phases are washed with sodium chloride solution, 1 N hydrochloric acid, NaHC03 solution and finally once more with sodium chloride solution. The solution is dried over sodium sulphate, the solvent is distilled off and the residue, dissolved in a little toluene, is then chromatographed on silica gel using toluene/ethyl acetate (20:1).
Yield: 1.82 g (90.4%) HPLC rt = 5.11 (96.0%) 0.01 M H3P0~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm MS (ESI): 409 ([M+H]'', I00%) Rf= 0.31 (toluene : ethyl acetate = 9:1) I,e A 34 254-Foreign Countries 200 MHz ~H-NlVRt (CDCl3): 1.85 (t, 3H); 1.24 (d, 3H); 1.43 (t, 3H); 1.53 -I.78 (m, 2H); 2.15 (s, 6H); 2.81 (quart, IH); 4.43 (quart, 2H); 6.72 (dd, IH); 6.86 (d, 1H);
6.93 (d, IH); 7.21 (d, 1H); 7.4 (s, 2H); 7.81 (s, IH); 8.8 (s, IH).
The compounds below (Examples 27 to 40) are prepared similarly to the procedure of Example 26:
Example 27 Ethyl N-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-dimethylphenyl]-oxamate Reactants:
12.78 g (43.41 mmol) of 4-(3-isopropyl-1H-indol-5-yloxy)-3,5-dimethylphenylamine 8.0 g (58.6 mmol) of ethyl oxalyl chloride 3.86 ml (47.75 mmol) of pyridine in 350 ml of dichloromethane Yield: 17.16 g (97.6%) MS (ESI): 3I5 ((M+H]~, 100%) Rf= 0.29 (toluene : ethyl acetate = 9:I) 300 MHz, ~H-NMR (CDC13): 1.26 (d, 6H); 1.43 (t, 3H); 2.17 (s, 6H); 3.06 (quin, 1H); 4.42 (quart, 2H); 6.73 (dd, 1H); 6.87 (d, 1H); 6.94 (d, 1H); 7.21 (d, IH); 7.39 (s, 2H); 7.78 (s, 1H); 8.78 (s, 1H).

Le A 34 254-Forei ~n Countries Example 28 Ethyl N-(4-(3-isobutyl-1H-indol-5-yloxy)-3,5-dimethylphenyl]-oxamate O
O
H H
O
Reactants:
0.13 g (0.41 mmol) of 4-(3-isobutyl-1H-indol-5-yloxy)-3,5-dimethylphenylamine 0.08 g (0.55 mmol) of ethyl oxalyl chloride 0.04 ml (0.49 mmol) of pyridine in 10 ml of dichloromethane Yield: 32.2 mg (19.5%) MS (ESI): 409 ([M+H]+, 12%) HPLC rt = 5.23 (77.6%) 0.5 % HC10~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Le A 34 254-Foreign Countries Example 29 N-[4-(3-Isobutyl-1H-indol-5-yloxy)-3,5-dimethylphenyl]-N'-methoxy-N'-methyl-oxalamide \ O ~ \ O
N.~ '~ N\
N
H H
O
Reactants:
80 mg (0.259 mmol) of 4-(3-isobutyl-IH-indol-5-yloxy)-3,5-dimethylphenylamine 0.025 ml (0.311 mmol) of pyridine 59 mg (0.389 mmol) of (methoxy-methylamino)-oxo-acetyl chloride in 6 ml of dichloromethane Yield: 85.2 mg (77.6%) MS (ESI): 424 ([M+H]+, 100%) I S HPLC: rt = 4.81 (94.6%) 0.5 % HC104/acetonitrile Kromasil column C 18 (60x2 mm) Flow rate: 0.75 ml/min; 2I0 nm Rf : 0.44 (toluene : ethyl acetate = 8:2) Ix A 34 254-Foreign Countries Examine 30 Ethyl N-[4-(3-isobutyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyIphenyl]-oxamate O
O~
n O
Reactants:
0.54 g (1.31 mmol) of 4-(3-isobutyl-IH-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenylamine 0.24 g ( 1.76 mmol) of ethyl oxalyl chloride 0.12 ml (1.44 mmol) of pyridine in 10 ml of dichloromethane Yield: 354 mg (52.5%) MS (ESI): 517 ([M+H]+, 100%) Rf = 0.34 (toluene : acetonitrile = 9: I ) Example 31 Ethyl N-(4-(3-sec-butyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenyl]-oxamate O
H H
O
Reactants:

Le A 34 254-Foreign Countries 170 mg (0.4 mmol) of 4-(3-sec-butyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenylamine 0.062 ml (0.44 mmol) of tziethylamine 0.062 ml (0.54 mmol) of ethyl oxalyl chloride S in 30 ml of dichloromethane Yield: 197.4 mg (93.8%) Rf=0.44 (dichloromethane) 200 MHz 'H-NMR (CDC13): 0.84 (t, 3H), 1.24 (d, 3H); 1.47 (t, 3H); 1.42 - 1.77 (m, 2H); 2.81 (quart, 1H); 4.47 (quart, 2H); 6.72 (dd, 1H); 6.83 (d, 1H); 6.94 (d, 1H);
7.22 (d, 1H); 7.83 (s, 1H); 8.24 (s, 2H); 9.09 (s, 1H).
Example 32 Ethyl N-(4-(3-(4-fluorophenyl)-1H-indol-5-yloxy}-3,5-bis-trifluoromethylphenyl]-oxamate F

O
N~F3C ~ H O
H O
Reactants:
mg (0.066 mmol) of 4-[3-(4-fluorophenyl)-1H-indol-5-yloxyJ-3,5-bis-trifluoromethylphenylamine 0.01 ml (0.073 mmol) of pyridine 25 0.01 ml (0.09 mmol) of ethyl oxalyl chloride Le A 34 254-Forei~ Countries in 10 ml of dichloromethane Yield: 23.6 mg (62.8%) MS (LC method, ES+): 572 ([M+NH4)+, 100%) HPLC: rt = 5.00 (97.4%) 0.5% HC104/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml /min; 210 nm Example 33 Ethyl N-[4-(3-methyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenyl)-oxamate ~ \ O \ O
N O
AFC ~ ~ N
H
O
Reactants:
270 mg (0.673 mmol) of 4-(3-methyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenylamine 0.06 ml (0.74 mmol) of pyridine 0.101 ml (0.91 mmol) of ethyl oxalyl chloride in 35 ml of dichloromethane Yield: 307.7 mg (93.3%) MS (DCI): 492 ([M+NH4)+, 100%) Rf = 0.17 (toluene : ethyl acetate = 9:1) HPLC rt = 4.88 (96.7%) 0.01 M H3P0~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Le A 34 254-Foreign Countries Example 34 Ethyl 4-[N-(3-cyclobutylmethyl-1 H-indol-5-yloxy)-3,5-bi s-trifluoromethylphenylJ-oxamate H
O

O
Reactants:
64 mg (0.I5 mmol) of 4-(3-cyclobutylmethyl-IH-indol-5-yloxy)-3,5-bis-trifluoromethylphenylamine 0.013 ml (0.16 mmol) of pyridine 0.023 ml (0.202 mol) of ethyl oxalyl chloride in I6 ml of dichloromethane Yield: 68 mg (77.9%) MS (ESI): 529 ([M+H]+, 42%) HPLC rt = 5.20 (90.4%) 0.5 % HCIO,~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Rf = 0.16 (toluene : ethyl acetate = 9:1 ) Le A 34 254-Foreign Countries Example 35 N-[4-(3-Isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenylJ-N'-methoxy-N'-methoxy-oxalamide N.O/
Reactants:
100 mg (0.249 mmol) of 4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenylamine 0.022 ml (0.273 mmol) of pyridine 51 mg (0.336 mmol) of (methoxy-methylamino)-oxo-acetyl chloride in 10 ml of dichloromethane Yield: 77.5 mg (60.3%) MS (ESI): 518 ([M+HJ+, 100%) 300 MHz'H-NMR (CDC13): 1.27 (d, 6H); 1.5 (s, 3H); 3.05 (quip, 1H); 3.84 (s, 3H);
6.73 (dd, 1H); 6.84 (d, 1H); 6.95 (d, 1H); 7.21 (d, 1H); 7.8 (s, 1H); 8.21 (s, 2H); 9.65 (s, 1 H).

Le A 34 254-Foreign Countries Example 36 N-[4-(3-sec-Butyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenyl]-C-oxo-C-thiophen-2-yl-acetamide O

O

~
~S

Reactants:
100 mg (0.24 mmol) of 4-(3-sec-butyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenylamine 21 p,1 (0.264 mmol) of pyridine 62.8 mg (0.36 mmol) of 2-thiophene glyoxyloyl chloride in 8 mI of dichloromethane Yield: 68 mg (51.1%) MS (LC method, ES+): 555 ([M+H]+, 100%) 300 MHz 'H-NMR (CDC13): 0.85 (t, 3H); 1.25 (d, 3H); 1.51 - 1.75 (m, 2H); 2.81 (quip, 1H); 6.72 (dd, 1H); 6.85 (d, 1H); 6.93 (d, 1H); 7.15 - 7.39 (m, 1H);
7.23 (d, 1H); 7.81 (s, 1H); 7.92 (dd, 1H); 8.32 (s, 2H); 8.53 (dd, 1H); 9.37 (s, 1H).

Le A 34 254-Forei gn Countries Example 37 N-[4-(3-Isopropyl-1 H-indol-5-yloxy)-3,5-bis-tri f luoromethylphenyl]-C-oxo-C-thiophen-2-yl-acetamide O
N S
I I
O
Reactants:
100 mg (0.248 mmol) of 4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenylamine 0.1 ml (1.236 mmol) of pyridine 86.8 mg (0.497 mmol) of 2-thiophenyl glyoxyloyl chloride in 5 ml of dichloromethane Yield: 69 mg (51.4%) MS (ESI): 541 ([M+H]+, 100%) 300 MHz 'H-NMR (CDC13): I.27 (d, 6H); 3.04 (quin, 1H); 6.73 (dd, 1H); 6.84 (d, IH); 6.93 (d, IH); 7.13 - 7.28 (m, 2H); 7.79 (s, 1H); 7.92 (dd, 1H}; 8.3 (s, 2H); 8.53 (dd, 1H); 9.35 (s, 1H}.

Le A 34 254-Foreign Countries Example 38 Ethyl N-[4-(3-methoxycarbonylmethyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenyl]-oxamate ~C
Reactants:
150 mg (0.347 mmol) of 4-(3-methoxycarbonyl-methyl-1H-indol-5-yloxy)-3,5-trifluoromethyl-phenylamine 0.031 ml (0.382 mol) of pyridine 0.052 ml (0.468 mmol) of ethyl oxalyl chloride in 10 ml of dichloromethane Yield: 118 mg (63.9%) MS (ESI): 532 ([M+H]+, 53%) HPLC rt = 4.75 (87.4%) 0.5% HCIO~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Le A 34 254-Foreign Countries s , Example 39 Methyl (DL)-2-acetylamino-3-(5-{2,6-bis-trifluoromethyl-4-[(1-ethoxycarbonyl-methanoyl)-amino]-phenoxy } -1 H-indol-3-yl)-propionate °J
N O
° ~ O

\ 'NH
O
Reactants:
218 mg (0.368 mmol) of methyl (DL)-2-acetylamino-3-[5-(4-amino-2,6-bis-trifluoromethyl-phenoxy)-1H-indol-3-yl]-propionate 0.033 ml (0.405 mmol) of pyridine 0.056 ml (0.497 mrnol) of ethyl oxalyl chloride in 15 ml of dichloromethane Yield: 171.9 mg (90.4%) MS (ESI): 604 ([M+H]+, 30%) R f = 0.23 (toluene : ethyl acetate = 1:2) HPLC rt = 4.42 0.5% HC10~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Le A 34 254-Foreign Countries Example 40 Methyl (DL)-2-acetylamino-3-(S-{2,6-dibromo-4-[(1-ethoxycarbonyl-methanoyl)-amino]-phenoxy } -1 H-indol-3-yl )-propionate Reactants:
219 mg (0.22 mmol) of methyl (DL)-2-acetylamino-3-[5-(4-amino-2,6-dibromo-phenoxy)-1H-indol-3-yl]-propionate 0.02 ml (0.242 mmol) of pyridine 0.034 ml (0.297 mmol) of ethyl oxalyl chloride in 10 ml of dichloromethane Yield: 100 mg (72.6%) MS (ESI): 646 ([M+Na]+, 72%) HPLC rt = 4.31 (92.4%) 0.5% HC10~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm 200 MHz 'H-NMR (CDC13): 1.44 (t, 3H); 1.93 (s, 3H); 3.21 (d, 2H); 3.68 (s, 3H);
4.45 (quart, 2H); 4.86 - 4.95 (m, 1H); 5.93 (d, 1H); 6.81 (dd, 2H); 6.99 (d, 1H); 7.3 (s and d, 3H); 8.04 (s, 1H); 8.9 (s, 1H).

Le A 34 254-Foreign Countries Example 41 N-[4-(3-Isopropyl-1H-indol-5-yloxy)-3,5-dimethyl-phenyl]-oxamic acid ~ O ~ ~ O
/ N OH
H H
O
Under argon, 12.4 g (31.43 mmol) of ethyl oxamate from Example 27 are dissolved in 1300 ml of dioxane, 330 ml of 1 molar aqueous sodium hydroxide solution are added and the mixture is stirred at room temperature for about 10 minutes (monitored by TLC for starting material). The reaction solution is then acidified with concentrated hydrochloric acid to pH 4, saturated with sodium chloride (test) and extracted four times with ethyl acetate. The combined organic phases are washed with sodium chloride solution, dried over sodium sulphate, filtered, concentrated and dried overnight under high vacuum. The substance is then dissolved in dichloromethane at 40°C and precipitated again by addition of a 10-fold amount of cyclohexane, filtered off with suction, washed with cyclohexane and dried at 70°C in a vacuum drying cabinet overnight.
Yield: 11.49 g (99.7%) MS (ESI): 367 ([M+H]+, 100%) 300 MHz ~H-NMR (d6-DMSO): 1.2 (d, 6H); 2.06 (s, 6H); 6.61 (dd, 1H); 6.71 (d, 1H); 7.03 (d, 1H); 7.22 (d, 1H); 7.53 (s, 2H); 10.43 (s, 1H); 10.61 (s, 1H).
Rf= 0.18 (dichloromethane/methanol = 9:1) The compounds below (Examples 42 and 43) are prepared similarly to the procedure of Example 41:

Le A 34 254-Foreign Countries Example 42 N-[4-(3-sec-Butyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenyl]-oxamic acid O
~ /J OH
N~F3C
H O
Reactants:
90 mg (0.174 mmol) of ethyl oxamate from Example 31 2.15 mg of 1 molar aqueous sodium hydroxide solution and 4.5 ml of dioxane Yield: 75.8 mg (87.3%) MS (LC method, ES+): 489 ([M+H]+, 15%) HPLC rt =4.76 (98.0%) 0.5 % HCIO~/acetonitrile Kromasil column C 18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Rf = 0.16 (ethyl acetate : methanol = 9:1 ) Example 43 N-[4-(3-sec-Butyl-1H-indol-5-yloxy)-3,5-dimethylphenyl]-oxamic acid O
OH
N
H H
O
Reactants:

L.e A 34 254-Foreign Countries 17 mg (0.042 mmol) of ethyl oxamate from Example 26 0.45 ml of I molar aqueous sodium hydroxide solution and 1.2 m1 of dioxane Yield: 15.8 mg (100%) MS (ES): 403 ([M+Na]+, 84%) 300 MHz'H-NMR (db-DMSO): 0.79 (t, 3H); 1.18 (d, 3H); 1.45 - 1.65 (m, 2H); 2.03 (s> 6H); 2.7 (quart, IH); 6.6 (dd, 1H); 6.7 (d, 1H); 7.05 (d, IH); 7.23 (d, IH); 7.55 (s, 2H); 10.37 (s, 1H); 10.68 (s, IH).
Example 44 Methyl N-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenyl]-ox am ate O
N~F3C
H O
At 40°C, 10 mg of ethyl N-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenyl]-oxamate (Example 4) are dissolved in IO ml of methanol, and the mixture is allowed to stand at room temperature overnight. The solvent is distilled off, giving the methyl ester in quantitative yield.
MS (DCI): 506 ([M+NH4]+, 100%) R f = 0.27 (toluene : ethyl acetate = 9:1 ) Le A 34 254-Foreign Countries Example 45 N-[4-(3-Isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenyl]-oxalamide H
N ( ~ O ( ~ O

H
O
200 mg (0.4 mmol) of ethyl N-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenyl]-oxamate (Example 4) are dissolved in 4 ml of methanol p.a., and ammonia is introduced at -10°C until saturation is reached. The solution is allowed to stand at room temperature for 4 days and then concentrated under reduced pressure, and the residue is dried under high vacuum.
Yield: 185.5 mg (98.4%) MS (ESI): 474 ([M+H]+, 100%) 200 MHz'H-NMR (d6-DMSO): 1.17 (d, 6H); 2.94 (quip, 1H); 6.61 (dd, 1H); 6.7 (d, 1H); 7.07 (d, 1H); 7.23 (d, 1H); 8.1 (s, 1H); 8.42 (s, 1H); 8.7 (s, 2H); 10.72 (d, 1H).
Example 46 N-Isopropyl-N'-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenyl]-oxalamide H
N I ~ O ~ ~ O
H

O

Le A 34 254-Foreign Countries 100 mg (0.2 mmol) of ethyl N-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenyl]-oxamate (Example 4) are dissolved in 3 ml of ethanol p.a., the mixture is cooled to 0°C and 0.136 ml (1.59 mmol) of isopropylamine is added under argon and with stirring. The solution is stirred at room temperature overnight and then concentrated to dryness. The residue is stirred in cyclohexane, filtered off with suction and dried under reduced pressure.
Yield: 85.7 mg (83.5%) MS (DCI): 533 ([M+NH4]+, 60%) 200 MHz'H-NMR (CDC13): 1.28 (dd, 12H); 3.05 (quin, 1H); 4.12 (m, 1H); 6.72 (dd, 1H); 6.84 (d, 1H); 6.94 (d, 1H); 7.21 (d, 1H); 7.36 (d, 1H); 7.8 (s, 1H); 8.28 (s, 2H);
9.67 (s, 1H).
The following compounds (Examples 47 and 48) are prepared similarly to the procedure of Example 46:
Example 47 N-Cyclopropyl-N'-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenyl]-oxalamide H
N ~ ~ O ~ ~ O
H
~/
/ FsC / N N
H O
Reactants:
100 mg (0.199 mmol) of ethyl N-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenyl]oxamate (Example 4) 0.11 ml (1.59 mmol) of cyclopropylamine in 4 ml of ethanol p.a.

Le A 34 254-Foreign Countries Yield: 84.6 mg (82.8%) MS (DCI): 531 ([M+NH4]+, 100%) 300 MHz'H-NMR (CDC13): 0,7 (m, 2H); 0.91 (m, 2H); 1.27 (d, 6H); 2.88 (m, 1H);
3.04 (quin, 1H); 6.71 (dd, 1H); 6.84 (d, 1H); 6.93 (d, 1H); 7.21 (d, 1H); 7.5 (s, 1H);
7.79 (s, 1H); 8.24 (s, 2H); 9.55 (s, 1H).
Example 48 N-[4-(3-Isopropyl-1H-indol-5-yloxy]-3,5-bis-trifluoromethyl-phenyl]-N',N'-dimethyl-oxalamide H
N I \ o I \ o I
~ F3C ~ N N\
H
O
Reactants:
100 mg (0.199 mmol) of ethyl N-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenyl]-oxamate (Example 4) 1.592 ml (1.592 mmol) of dimethylamine as a 2.0 molar solution in tetrahydrofuran in 3 ml of ethanol p.a.
Yield: 90.7 mg (90.9%) MS (DCI): 519 ([M+NH4]+, 100%) 300 MHz ~H-NMR (CDC13): 1.27 (d, 6H); 3.04 (quart, :H); 3.11 (s, 3H); 3.55 (s, 3H); 6.71 (dd, 1H); 6.85 (d, 1H); 6.93 (d, 1H); 7.20 (d, 1H); 7.79 (s, 1H);
8.21 (s, 2H); 9.65 (s, 1H).

Ix A 34 254-Foreign Countries Example 49 N-(2-Hydroxyethyl)-N'-[4-(3-isopropyl-1 H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenyl]-oxalamide OOH
Reactants:
100 mg (0.199 mmol) of ethyl N-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenyl]-oxamate (Example 4) 0.12 ml (1.99 mmol) of 2-aminoethanol in 4 ml of ethanol p.a.
Yield: 60 mg (51.6%) MS (ESI): 518 ([M+H]+, 100%) 300 MHz ~H-NMR (d~-DMSO): 1.19 (d, 6H); 2.95 (quip, 1H); 3.17 - 3.34 (m, 2H);
3.41 - 3.55 (m, 2H); 4.73 (sext, 1H); 6.61 (dd, 1H); 6.71 (d, 1H); 7.06 (d, 1H); 7.23 (d, 1H); 8.52 (m, 1H); 8.7 (s, 2H); 8.88 (t, 1H); 10.7 (d, 1H).
Rf = 0.12 (toluene : ethyl acetate = 8:2) Example 50 N-[4-(3-Isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethyl-phenyl]-N'-methyl-oxalamide H
O
H
~ F3C
H
O

Le A 34 254-Foreign Countries Reactants:
100 mg (0.199 mmol) of ethyl N-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenyl]-oxamate (Example 4) 0.498 ml (0.995 mmol) of methylamine as a 2 molar solution in tetrahydrofuran in 3 ml of ethanol p.a.
Yield: 79.3 mg (81.7%) MS (LC method, ES+): 488 ([M+H]+, 100%) R~ = 0.33 (toluene : ethyl acetate = 8:2) 300 MHz ~H-NMR (db-DMSO): 1.18 (d, 6H); 2.75 (d, 3H); 2.97 (quin, 1H); 6.61 (dd, 1H); 6.71 (d, 1H); 7.05 (d, 1H); 7.23 (d, 1H); 8.7 (s, 2H), 9.0 (s, 1H);

10.69 (s, 1H); 11.31 (s, 1H).
Example 51 N-(2-Hydroxy-1,1-bis-hydroxymethyl-ethyl)-N'-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenyl]-oxalamide H
N ~ ~ O ~ ~ O
H
~ F3C ~ N N~C(CH20H)3 H
O
100 mg (0.199 mmol) of ethyl N-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenyl]-oxamate (Example 4) 241 mg (1.99 mmol) of tris-(hydroxymethyl)-methylamine in 4 ml of ethanol and 0.3 ml of water Yield: 30.8 mg (26.8%) MS (DCI): 594 ([M+NHa]+, 64%) Rf = 0.5 (toluene : ethyl acetate = 1:9) Le A 34 254-Foreign Countries Example 52 N-(2-Hydroxy-propyl)-N'-(4-(3-isopropyl-1H-indol-5-yloxy)-bis-trifluoromethyl-phenyl]-oxalamide H
N ~ ~ O ~ ~ O OH
H
/ FsC / N N
H I
O
Reactants:
80 mg (0.159 mmol) of ethyl N-[4-(3-isopropyl-1H-indol-5-yloxy)-3,5-bis-trifluoromethylphenyl]-oxamate (Example 4) 0.123 ml (1.59 mmol) of 1-amino-2-propanol in 4 ml of ethanol p.a.
Yield: 36.8 mg (43.5%) MS (ESI): 532 ([M+H]+, 100%) HPLC rt = 4.78 (100%) 0.5 % HC10~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min; 210 nm Le A 34 254-Foreign Countries Example 53 N-[4-(3-Isopropyl-1H-indol-5-yloxy)-3,5-dimethyl-phenyl]-oxalamide O ~ O

N
H
O
Reactants:
100 mg (0.240 mmol) of the ethyl oxamate from Example 27 Addition of ammonia until saturation is reached in 10 ml of ethanol p.a.
Yield: 87.7 mg (100%) MS (ESI): 366 ([M+H]+, 100%) HPLC rt = 4.58 (100%) 0.5% HC10~/acetonitrile Kromasil column C18 (60x2 mm) Flow rate: 0.75 ml/min, 210 nm Example 54 Ethyl f(3 5-dibromo-4-f f 1H-indol-5-ylloxy~phenyl)aminol(oxo)acetate Br O ~ ~ O
~ /J O
H~ Br O
With ice-cooling, a solution of 656 mg (4.81 mmol) of ethyl oxalyl chloride in 5 ml of dichloromethane is added dropwise to a suspension of 1.67 g (4.37 mmol) of 5-(4-amino-2,6-dibromophenoxy)-1H-indole and 531 mg (5.25 mmol) of triethylamine in Le A 34 254-Foreign Countries 20 ml of dichloromethane. The mixture is stirred at room temperature for 30 min and the organic phase is then washed lx with water and dried over sodium sulphate.
Removal of the solvent under reduced pressure gives 2.13 g (87°10) of ethyl [(3,5-dibromo-4-{[1H-indol-5-yl]oxy}phenyl)amino](oxo)acetate in good purity.
300 MHz 'H-NMR (DMSO): 1.33, t, 3H; 4.33, q, 2H; 6.32, m, 1H; 6.71, m, 2H;
6.74, dd, 1H; 7.33> m, 1H; 7.35, d, 1H; 8.22, s, ZH; 11.05, s, broad, 1H;

11.10, s, broad, 1 H.
Example 55 Etyl f(3 5-dibromo-4-( f3-cyclohexylcarbonyl-1H-indol-5-ylloxylnhenyl)aminol-oxo)acetate O
Br \ O \ O
O
Br H H I
O
9.9 mg (0.071 mmol) of ethyl oxalyl chloride are added to a solution of 35 mg (0.071 mmol) of 5-(4-amino-2,6-dibromophenoxy)-3-cyclohexylcarbonyl-1H-indole and 6.5 mg (0.064 mmol) of triethylamine in 2 ml of dichloromethane, and the mixture is stirred at room temperature overnight. Another 4.9 mg (0.035 mmol) of ethyl oxalyl chloride and 1 mg of 4-dimethylaminopyridine are then added, and the mixture is stirred at room temperature for another 12 h. The crude product is then purified on silica gel 60 (cyclohexane/ethyl acetate 3:1 - 1:1), giving 25 mg (59%) of ethyl [(3,5-dibromo-4-{[3-(4-cyclohexylcarbonyl)-1H-indol-5-yl]oxy}phenyl)-amino](oxo)acetate.
200 MHz ~H-NMR (DMSO): 1.33, t, 3H; 1.35, m, 5H; 1.70, m, 5H; 3.10, m, 1H;
4.34, q, 2H; 6.92, dd, 1H; 7.37, d, 1H; 7.46, d, 1H; 7.95, s, 1H; 8.25, s, 1H;
8.35, s, 1H; 11.14, s, broad, 1H; 11.95, s, broad, 1H.

Le A 34 254-Forei,a~.n Countries Example 56 Ethyl [(3,5-dibromo-4-{[3-isopropylcarbonyl-1H-indol-5-yl]oxy}phenyl)amino]-(oxo)acetate O
O~
h N
H
O
In a similar manner, 40 mg (0.088 mmol) of 5-(4-amino-2,6-dibromophenoxy)-3-iso-propylcarbonyl-1H-indole, 8.0 mg (0.080 mmol) of triethylamine, 17.8 mg (0.130 mmol) of ethyl oxalyl chloride and 1 mg of 4-dimethylaminopyridine are reacted in 2 ml of dichloromethane and 3 drops of DMF to give 47 mg (96°10) of ethyl [(3,5-dibromo-4-{ [3-(4-isopropylcarbonyl)-1H-indol-5-yl]oxy}phenyl)amino]-(oxo)acetate.
200 MHz 'H-NMR (DMSO): 1.08, d, 6H; 1.35, t, 3H; 3.39, sept, 1H; 4.33, q, 2H;
6.92, dd, 1H; 7.38, d, 1H; 7.45, d, 1H; 7.96, s, 1H; 8.25, s, 1H; 8.35, d, 1H;
11.15, s, broad, 1H; 11.96, s, broad, 1H.
Examule 57 Ethyl [(3,5-dibromo-4-{ [3-(N-benzyl-N-isopropylamino)methyl-1H-indol-5-yl]oxy } phenyl)amino] (oxo)acetate N
Br \ O ~ \ O.
H~ Br ~ H O\/
O
31.4 mg (0.23 mmol) of ethyl oxalyl chloride are added to a solution of 119 mg (0.22 mmol) of 5-(4-amino-2,6-dibromophenoxy)-3-(N-benzyl-N-isopropyl-aminomethyl)-1H-indole and 19.9 mg (0.20 mmol) of triethylamine in 2 ml of Le A 34 254-Foreign Countries dichloromethane, and the mixture is stirred at room temperature for 15 min. 1 ml of sat. NaHC03 solution is then added, the aqueous phase is extracted 2x with dichloromethane and the combined organic extracts are dried over sodium sulphate and, under reduced pressure, freed from solvent. Purification of the residue on silica S gel 60 (cyclohexane/ethyl acetate 10:1 - 1:l) gives 84.4 mg (60%) of ethyl [(3,5-dibromo-4-( [3-(N-benzyl-N-isopropylamino)methyl-1H-indol-5-yl]oxy}phenyl)-amino](oxo)acetate.
200 MHz ~H-NMR (DMSO): 0.88, d, 6H; 1.31, t, 2.75, sept, 1H; 3.40, s, 2H;
3.49, s, 2H; 4.30, q, 2H; 6.87, dd, 1H; 6.91, d, IH; 7.I5, m, 6H; 7.30, d, IH; 7.96, s, 1H;
8.30, s, 2H; 10.74, s, broad, IH; I 1.10, s, broad, 1H.
Example 58 Ethyl [(3,5-dibromo-4-{ [3-(N-benzyl-N-ethylamino)methyl-1H-indol-5-yl]oxy}phenyl)amino](oxo)acetate / \
O
O~
h N
H
O
Similarly, from 183 mg (0.346 mmol) of 5-(4-amino-2,6-dibromophenoxy)-3-(N-benzyl-N-ethyl-aminomethyl)-1H-indole, 31.5 mg (0.311 mmol) of triethylamine and 51.9 mg (0.380 mmol) of ethyl oxalyl chloride in 2 ml of dichloromethane, and following two purifications of the crude product on silica gel 60 (dichloromethane -dichloromethane/methanol 10:I), 40 mg (16%) of ethyl [(3,5-dibromo-4-{[3-(N-benzyl-N-ethylamino)methyl-1H-indol-5-yl]oxy}phenyl)amino](oxo)acetate are obtained.

Le A 34 254-Foreigyn Countries 300 MHz 'H-NMR (DMSO): 0.88, t, 3H; 1.32, t, 3H; 2.28, q, 2H; 3.41, s, 2H;
3.50, s, 2H; 4.32, q, 2H; 6.83, dd, 1H; 6.90, d, 1H; 7.18, m, 7H; 7.30, d, 1H; 8.30, s, 2H;
10.83, d, broad, 1H; 11.12, s, broad, 1H.
Example 59 Ethyl [(3,5-dibromo-4-{ [3-(N-4-fluorobenzyl-N-cyclopentylamino)methyl-1H-indol-5-yl]oxy}phenyl)amino](oxo)acetate F
O
H
O
6 fCl (0.069 mmol) of 35% strength formaldehyde solution are added to a solution of 20 mg (0.041 mmol) of ethyl [(3,5-dibromo-4-{[IH-indol-5-ylJoxy}phenyl)-aminoJ(oxo)acetate and 8.8 mg (0.046 mmol) of 4-fluorobenzylcyclopentylamine in 0.5 ml of dioxane and 0.1 ml of acetic acid. The solution is stirred at room temperature for 1 h and then mixed with NaHC03 solution, the aqueous phase is extracted with ethyl acetate and the combined organic extracts are, under reduced pressure, freed from the solvent. Purification on silica gel 60 (dichloromethane -dichloromethane/methanol 10:1) gives 10 mg (35%) of ethyl [(3,5-dibromo-4-{[3-(N-4-fluorobenzyl-N-cyclopentylamino)methyl-1H-indol-5-yl]oxy } phenyl)amino]-(oxo)acetate.
300 MHz 'H-NMR (DMSO): 1.32, t, 3H; 1.33, m, 4H; 1.48, m, 4H; 2.95, m, 1H;
3.43, s, 2H; 3.51, s, 2H; 4.32, q, 2H; 6.82, d, 1H; 6.87, dd, IH; 6.99, dd, 2H; 7.11, dd, 2H; 7.2I, d, 1H; 7.30, d, IH; 8.3I, s, ZH; 10.80, d, broad, 1H; 11.15, s, broad, 1H.
Example 60 Le A 34 254-Foreign Countries Ethyl f(3.5-dibromo-4-((3-(4-morpholinyl)methyl-1H-indol-5-ylloxylphenY)-aminol(oxo)acetate O
N
Br O ~ ~ O
H~ Br ~ H O~
O
In a similar manner, 20 mg (0.041 mmol) of ethyl [(3,5-dibromo-4-{[1H-indol-5-yl]oxy}phenyl)amino](oxo)acetate, 4.3 mg (0.050 mmol) of morpholine and 3.6 p,1 (0.046 mmol) of 35% strength formaldehyde solution in 0.5 ml of dioxane and 0.1 ml of acetic acid gives, after chromatographic purification (silica gel 60, ethyl acetate -dichloromethane/methanol 5:1), 18 mg (67%) of ethyl [(3,5-dibromo-4-{ [3-(4-morpholinyl)methyl-1H-indol-5-yl]oxy}phenyl)amino](oxo)acetate.
300 MHz ~H-NMR (DMSO): 1.32, t, 3H; 2.28, m, 4H; 3.47, m, 4H; 3.50, s, 2H;
4.33, q, 2H; 6.70, dd, 1H; 6.95, d, 1H; 7.21, d, 1H; 7.29, d, 1H; 8.23, s, 2H;
10.88, d, broad, 1 H; 11.10, s, broad, 1 H.
Example 61 Ethyl ((3,5-dibromo-4-((3-(1-piperidyl)methyl-1H-indol-5- 1y fox 1y phenyl)amimol-(oxo)acetate N~
Br O
H~ Br ~ ~ O~' O

Le A 34 254-Forei an Countries Example 61 Et~l f~,5-dibromo-4-(f3-(1-piperidyl)methyl-1H-indol-5- lloxylphenyl)aminol-(oxo)acetate N~
Br O ~ ~ O
H~ Br O
In a similar manner, 20 mg (0.041 mmol) of ethyl [(3,5-dibromo-4-{ [1H-indoI-5-yI]oxy}phenyl)amino](oxo)acetate, 4.2 mg (0.050 mmol) of piperidine and 3.6 u1 (0.046 mmol) of 35% strength formaldehyde solution in 0.5 ml of dioxane and 0.1 ml of acetic acid give, after chromatographic purification (silica gel 60, ethyl acetate/triethylamine 20:I), 10 mg (42°l0) of ethyl [(3,5-dibromo-4-{[(1 piperidyl)methyl-1H-indol-5-y1]oxy}phenyl)amino](oxo)acetate.
300 MHz 'H-NMR (DMSO): 1.32, t, 3H; 1.35, m, 6H; 2.25, m, 4H; 3.46, s, 2H;
4.33, q, 2H; 6.70, dd, 1H; 6.95, d, 1H; 7.18, d, 1H; 7.27, d, 1H; 8.23, s, 2H;
10.83, d, broad, 1H; 11.10, s, broad, 1H.
Example 62 I(3,5-Dibromo-4-( f 3-(1-pyrrolidinyl)methyl-1H-indol-5 girl]oxylphenyl)aminol-(oxo)acetic acid) ,N
Br O
H~ Br ~ H O

Le A 34 254-Forei.Qn Countries In a similar manner, 20 mg (0.041 mmol) of ethyl [(3,5-dibromo-4-{ [IH-indol-5-yl]oxy}phenyl)amino](oxo)acetate, 3.5 mg (0.050 mmol) of pyrrolidine and 3.6 ~,1 (0.046 mmol) of 35% strength formaldehyde solution in 0.5 ml of dioxane and 0.1 ml of acetic acid give, after chromatographic purification (silica gel 60, dichloro-methane/methanol 20:1 + 5% triethylamine) and recrystallization from dichloromethane, 5.9 mg (26%) of [(3,5-dibromo-4-{ [(1-pyrrolidinyl)methyl-1H-indol-5-yl]oxy}phenyl)amino](oxo)acetic acid.
300 MHz 'H-NMR (DMSO): 1.86, m, 4H; 3.I0, m, 4H; 4.38, m, 2H; 6.71, dd, 1H;
IO 7.12, d, 1H; 7.37, d, 1H; 7.57, d, 1H; 8.26, s, 2H; 10.28, s, broad, 1H;
10.46, s, broad, 1 H; 11.40, s, broad, 1 H.
Example 63 [(3,5-Dibromo-4-i (3-(dieth~amino methyl-IH-indol-5-ylloxylphenyl)aminol-(oxo)acetic acid O
O
n N
H
O
In a similar manner, 20 mg (0.041 mmol) of ethyl [(3,5-dibromo-4-{[1H-indol-5-yl]oxy}phenyl)amino](oxo)acetate, 3.6 mg (0.050 mmol) of diethylamine and 3.6 ~1 (0.046 mmol) of 35% strength formaldehyde solution in 0.5 ml of dioxane and 0.1 ml of acetic acid give, after purification by HPLC, 9.3 mg (42%) of [(3,5-dibromo-{[(diethylamino)methyl-1H-indol-5-yl]oxy}phenyl)amino](oxo)acetic acid.
300 MHz 'H-NMR (DMSO): 1.20, m, 6H; 3.00, m, 4H; 4.37, m, 2H; 6.79, dd, 1H;
6.96, d, 1H; 7.40, d, 1H; 7.60, m, 1H; 8.28, s, 2H; 9.37, s, broad, 1H; 10.46, s, broad, 1 H; 11.50, s, broad, 1 H.

Le A 34 254-Foreign Countries Example 64 j~3 5-Dibromo-4-( f3-(diethylamino)methyl-1H-indol-5-ylloxylphenyl)aminol-(oxo)acetic acid H-N-Br O
H~ Br ~ H O
O
In a similar manner, 20 mg (0.041 mmol) of ethyl [(3,5-dibromo-4-{[1H-indol-5-yl]oxy}phenyl)amino](oxo)acetate, 5.6 mg (0.050 mmol) of 40% strength dimethylamine solution and 3.6 ~1 (0.046 mmol) of 35% strength formaldehyde solution in 0.5 ml of dioxane and O.I ml of acetic acid give, after purification by HPLC, 5.7 mg (27%) of [(3,5-dibromo-4-{ [(dimethylamino)methyl-1H-indol-5-yl]oxy}phenyl)amino](oxo)acetic acid.
300 MHz ~H-NMR (DMSO): 2.65, m, 6H; 4.30, m, 2H; 6.72, dd, 1H; 7.10, d, 1H;
7.39, d, 1H; 7.55, d, 1H; 8.27, s, 2H; 9.92, s, broad, 1H; 10.47, s, broad, 1H; 11.42, s, broad, 1H.
Example 65 j~3 5-Dibromo-4-( 3-(N-bend-N-isopropylamino)methyl-1H-indol-5-ylloxy~phenyl)aminol(oxo)acetic acid hydrochloride ", O
OH
N
H
O

Le A 34 254-Foreign Countries A solution of 20 mg (0.031 mmol) of ethyl [(3,5-dibromo-4-{ [3-(N-benzyl-N-iso-propylamino)methyl-1H-indol-5-yl]oxy}phenyl)amino](oxo)acetate in I ml of dioxane is admixed with 0.31 ml of 1N aqueous sodium hydroxide solution (0.31 mmol) and stirred at room temperature for 1 h. The mixture is then adjusted to pH 2 using 1N hydrochloric acid, the aqueous phase is extracted 3x with ethyl acetate and the combined organic extracts are dried over Na2S04 and, under reduced pressure, freed from the solvent. This gives 20.2 mg (100°!0) of [(3,5-dibromo-4-{ (3-(N-benzyl-N-isopropylamino)methyl-1H-indol-5-yl]oxy}phenyl)amino](oxo)acetic acid hydrochloride.
200 MHz'H-NMR (DMSO): 1.36> d, 6H; 1.31, t, 3.45, m, 1H; 4.18, m, 2H; 4.46, m, 2H; 6.74, d, 1H; 6.80, m, 1H; 7.50, m, 7H; 8.28, s, 2H; 9.26, s, broad, 1H;
10.98, s, broad, 1H; l I.52, s, broad, 1H.
Example 66 ((3,5-Dibromo-4-( (1H-indol-5:ylloxy}phenyl)aminol(oxo)-N-~-hydrox'yethyl)-acetamide Br O
~ ~~ H
N~ gr ~ N N~OH
H H I
O
A solution of SO mg (0.104 mmol) of ethyl [(3,5-dibromo-4-{[1H-indol-5-yl]oxy}-phenyl)amino](oxo)acetate and 9.5 mg (0.156 mmol) of aminoethanol in 1 ml of THF is stirred at room temperature for 2 h. The solvent is then removed under reduced pressure and the residue that remains is purified on silica gel 60 (ethyl acetate). This gives 44.5 mg (86%) of [(3,5-dibromo-4-{[1H-indol-5-yl)oxy}-phenyl)amino](oxo)-N-(2-hydroxyethyl)acetamide.

Le A 34 254-Foreign Countries 300 MHz 'H-NMR..(DMSO): 3.29, q, 2H; 3.51, q, 2H; 4.76, t, IH; 6.31, t, 1H;
6.72, s, 1H; 6.73, dd, 1H; 7.30, d, 1H; 7.33, d, 1H; 8.29, s, 2H; 8.85, t, 1H;
11.01, m, broad, 2H.
S Example 67 Methyl N-f(3 5-dibromo-4-( f IH-indol-5-ylloxylphenyl)aminoi(oxo)acetyl~l cinate O~
A solution of 50 mg (0.104 mmol) of ethyl [(3,5-dibromo-4-{(1H-indol-5-ylJoxy}-phenyl)aminoJ(oxo)acetate, 19.5 mg (0.156 mmol) of methyl glycinate hydrochloride and 31.5 mg (0.311 mmol) of triethylamine in 1.5 ml of THF is heated at reflux for 24 h. The solvent is then removed under reduced pressure and the residue that remains is purified on silica gel 60 (dichloromethane). This gives 35.5 mg (65%) of methyl N-[(3,5-dibromo-4-{[IH-indol-5-ylJoxy}phenyl)aminoJ(oxo)acetyl-glycinate.
300 MHz ~H-NMR (DMSO): 3.69, s, 3H; 4.00, d, 2H; 6.31, t, 1H; 6.72, s, 1H;
6.73, dd, 1H; 7.30, d, 1H; 7.33, d, 1H; 8.30, s, 2H; 9.34, t, 1H; 11.01, s, broad, 1H; 11.06, s, broad, 1H.

Le A 34 2S4-Foreign Countries Example 68 tent-Butyl N-f (3,S-dibromo-4- f f IH-indol-S-yllox~phenyl)aminol(oxo)acetyl=
glycinate \ O
"~ E v _O
H
S
A solution of 50 mg (0.104 mmol) of ethyl [(3,S-dibromo-4-{ [1H-indol-S-yl]oxy}phenyl)amino](oxo)acetate, 26.1 mg (0.1S6 mmvl) of ten-butyl glycinate hydrochloride and 31.5 mg (0.311 mmot) of triethylamine in 1.S ml of THF is heated at reflux for 24 h. The solvent is then removed under reduced pressure and the residue that remains is purified on silica gel 60 (dichloromethane). This gives 45.6 mg (78%) of tent-butyl N-[(3,S-dibromo-4-{[1H-indol-S-yl]oxy}phenyl)aminoJ-(oxo)acetylglycinate.
300 MHz 'H-NMR (DMSO): 1.43, s, 9H; 3.87, d, 2H; 6.31, t, 1H; 6.72, s, 1H;
6.73, 1S dd, 1H; 7.30, d, 1H; 7.34, d, 1H; 8.30, s, 2H; 9.23, t, 1H; 11.02, s, broad, IH; 11.07, s, broad, 1 H.
Example 69 Methyl N-( f4-( f3-(isopropylLlH-indol-S- l~oxyf-3 S-bis(trifluoromethyl)phenyll-amino 1 (oxo)acetyl ~lycinate O~

Le A 34 254-Foreign Countries A solution of 35 mg (0.070 mmol) of ethyl { [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]amino}(oxo)acetate, I7.5 mg (0.139 mmol) of methyl glycinate hydrochloride and 21.1 mg (0.209 mmol) of triethylamine in 1.5 ml of THF is heated at reflux for 48 h. The solvent is then removed under reduced pressure and the residue which remains is purified on silica gel 60 (dichloromethane).
This gives 36.2 mg (95%) of methyl N-{ [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]amino } (oxo)acetylglycinate.
300 MHz ~H-NMR (DMSO): 1.I9, d, 6H; 2.97, sept, IH; 3.68, s, 3H; 4.0I, d, 2H;
6.62, dd, 1H; 6.73, d, 1H; 7.08, d, 1H; 7.24, d, 1H; 8.70, s, 2H; 9.38, t, 1H;
10.70, s, broad, 1H; 11.40, s, broad, IH.
Example 70 N-( f4-~ [3-(Isopropyl)-IH-indol-5- 1y loxy~-3.5-bis(trifluoro-methyl)phenyllaminol-(oxo)acetylserine methyl ester F
F F
O H O
N~F ~ N N O/
H
F F H O
OH
Analogously, 35 mg (0.070 mmol) of ethyl { [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]amino}(oxo)acetate, 21.7 mg (0.139 mmol) of serine methyl ester hydrochloride and 21.1 mg (0.209 mmol) of triethylamine in 1.5 ml of THF give 35.7 mg (89%) of N-{ [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoromethyl)phenyl]amino}(oxo)acetylserine methyl ester.
300 MHz 'H-NMR (DMSO): 1.19, d, 6H; 2.97, sept, 1H; 3.69, s, 3H; 3.84, m, 2H;
4.50, dt, 1H; S.I9, t, IH; 6.62, dd, IH; 6.73, d, IH; 7.08, d, 1H; 7.24, d, IH; 8.70, s, 2H; 8.95, d, 1H; 10.70, d, broad, 1H; 11.43, s, broad, IH.

Le A 34 254-Foreign Countries Example 71 ten-Bu~l N-1 f4-~ f3-(isopropyl)-1H-indol-5-ylloxy~-3.5-bis(trifluoro-methyl)-phenyllamino 1 (oxo)acetylQlycinate F
F F
O H O
N~F ~ N N v 'O
H H I
F F O
A solution of 100 mg (0.199 mmol) of ethyl-{ [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]amino}(oxo)acetate, 66.7 mg (0.398 mmol) of tert-butyl glycinate hydrochloride, 60.3 mg (0.59? mmol) of triethylamine and 0.2 mg (0.002 mmol) of DMAP in 2 ml of THF is heated at reflux for 24 h. The solvent is then removed under reduced pressure and the residue that remains is purified on silica gel 60 (dichloromethane). This gives 115 mg (98°l0) of tent-butyl N-{ [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy }-3,5-bis(trifluoro-methyl)phenyl]amino }
(oxo)acetyl-glycinate.
400 MHz 'H-NMR (CDC13): 1.27, d, 6H; 1.51, s, 9H; 3.06, sept, 1H; 4.07, d, 2H;
6.73, dd, 1H; 6.85, d, 1H; 6.95, d, 1H; 7.22, d, 1H; 7.81, s, broad, 1H; 7.91, t, 1H;
8.26, s, 2H; 9.45, s, broad, 1H.
Example 72 N-~ (4-( (3-(Is~rop_yl)-1H-indol-5 yllox~3,5-bis(trifluoro-methyl)phenyllaminol-(oxo)acetylthreonine meth 1y ester O O
H
N N O~
H
O
OH

Le A 34 254-Foreign Countries Analogously, 100 mg (0.199 mmol) of ethyl { [4-( [3-(Isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]amino}(oxo)acetate, 67.5 mg (0.398 mmol) of threonine methyl ester hydrochloride, 60.3 mg (0.597 mmol) of triethylamine and 0.2 mg (0.002 mmol) of DMAP in 2 m1 of THF give 85 mg (72%) of N-{ [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl)amino}(oxo)acetyl-threonine methyl ester.
400 MHz 'H-NMR (CDC13): 1.27, d, 6H; 1.29, t, 3H; 1.99, d, 1H; 3.07, sept, 1H;
3.82, s, 3H; 4.50, dq, 1H; 4.60, dd, 1H; 6.72, dd, 1H; 6.83, d, 1H; 6.95, d, 1H; 7.22, d, 1H; 7.80, s, broad, 1H; 8.I3, d, broad, 1H; 8.28, s, 2H; 9.43, s, broad, 1H.
Example 73 N-( (4-( (3-(Iso~ropyl)-1H-indol-5- 1y loxyl-3,5-bis(trifluoromethyl)phenyll-amino)(oxo)acetyltyrosine meth 1 F
F F
O I \ O hi O
H~F / H N O/
F F O
/
OH
Analogously, 100 mg (0.199 mmol) of ethyl { [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}
3,5-bis(trifluoro-methyl)phenyl]amino}(oxo)acetate, 92.2 mg (0.398 mmol) of tyrosine methyl ester hydrochloride, 60.3 mg (0.597 mmol) of triethylamine and 0.2 mg (0.002 mmol) of DMAP in 2 ml of THF gi ve 122 mg (94%) of N-{ [4-{ [3 (isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]amino}(oxo) acetyltyrosine methyl ester.
200 MHz ~H-NMR (CDC13): 1.27, d, 6H; 3.05, sept, 1H; 3.13, t, 2H; 3.72, s, 1H;
3.78, s, 3H; 4.84, dt, 1H; 6.72, dd, 1H; 6.78, d, 2H; 6.83, d, 1H; 6.95, d, 1H; 7.02, d, Le A 34 254-Foreign Countries 2H; 7.21, d, 1H; 7.81, s, broad, 1H; 7.88, d, broad, 1H; 8.24, s, 2H; 9.39, s, broad, 1 H.
Example 74 N ( f4 t f3-(Isopro~yl)-1H-indol-5-ylloxyl-3 5-bis(trifluoro-methyl)phenyllaminol-(oxo)acetylalanine methyl ester F
F F
\ O ~ \ O H O
N~ ~ N N
F F H O
Analogously, 100 mg (0.199 mmol) of ethyl { [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]amino}(oxo)acetate, 55.6 mg (0.398 mmol) of tyrosine methyl ester hydrochloride, 60.3 mg (0.597 mmol) of triethylamine and 0.2 mg (0.002 mmol) of DMAP in 2 ml of THF give 93 mg (84%) of N-{ [4-{ [3-(isopropyl)-1 H-indol-5-yl]oxy }-3,5-bis(trifluoro-methyl)phenyl]amino } (oxo)-acetylalanine methyl ester.
300 MHz ~H-NMR (CDCl3): 1.27, d, 6H; 1.55, d, 3H; 3.05, sept, 1H; 3.80, s, 3H;
4.64, dq, 1H; 6.72, dd, 1H; 6.84, d, 1H; 6.94, d, 1H; 7.21, d, 1H; 7.79, s, broad, 1H;
7.97, d, broad, 1H; 8.26, s, 2H; 9.43, s, broad, 1H.

Le A 34 254-Foreign Countries Example 75 N ( f4 ( f3 (IsoproQyl)-1H-indol-5-ylloxy~-3 5-bis(tr-ifluoro-methyl)phenyllaminol-~oxo)acetylleucine methyl ester F
F F
\ O I \ O H O
~ 'J N /
O
F F O
Analogously, 100 mg (0.199 mmol) of ethyl-{ [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]amino}(oxo)acetate, 72.3 mg (0.398 mmol) of leucine methyl ester hydrochloride, 60.3 mg (0.597 mmol) of triethylamine and 0.2 mg (0.002 mmol) of DMAP in 2 ml of THF give 84 mg (70%) of N-{ [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(tr-ifluoro-methyl)phenyl]amino}(oxo)acetyl-leucine methyl ester.
200 MHz 'H-NMR (DMSO): 0.90, t, 6H; 1.19, d, 6H; 1.62, m, 2H; 1.89, m, 1H;
2.95, sept, 1H; 3.67, s, 3H; 4.46, m, 1H; 6.64, dd, 1H; 6.71, d, 1H; 7.08, d, 1H; 7.25, d, 1H; 8.70, s, 2H; 9.42, d, broad, 1H; 10.74, d, broad, 1H; 11.42, s, broad, 1H.
Example 76 Methyl 2-({ f4-f f3-(isopropyl)-1H-indol-5-ylloxy}-3 5-bis(trifluoromethyl)nhenyll-amino ) (oxo)acetylamino)-6-tent-butoxycarbonylamino-hexanoate O O
H
N N O~
O N O
O

L.e A 34 254-Foreign Countries Analogously, 100 mg (0.199 mmol) of ethyl { [4-{ [3-(Isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]amino}(oxo)acetate, 118.1 mg (0.398 mmol) of 6-Boc-lysine methyl ester hydrochloride, 60.3 mg (0.597 mmol) of triethylamine and 0.2 mg (0.002 mmol) of DMAP in 2 ml of THF give 106 mg (74%) of methyl 2-({ [4-{[3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoromethyl)phenyl]amino}-(oxo)acetylamino)-6-tent-butoxycarbonylamino-hexanoate.
300 MHz ~H-NMR (CDC13): 1.27, d, 6H; 1.40, m, 2H; 1.44, s. 9H; 1.54, m, 2H;
1.85> m, 1H; 2.00, m, 1H; 3.05, quint, 1H; 3.10, q, 2H; 3.79, s, 3H; 4.53, m, 1H;
4.63, m, 1H; 6.73, dd, 1H; 6.85, d, 1H; 9.94, d, 1H; 7.22, d, 1H; 7.81, s, broad, 1H;
7.94, d, broad, 1 H; 8.26, s, 2H; 9.43, s, broad, 1 H.
Example 77 Methyl 2-( f4-~(3-(isopropyl)-1H-indol-S- l~y~-3,5-bis(trifluoro-methyl)phenyll-amino)(oxo)acetylamino-3-(4-imidazolyl)-methylpropionate O O
H
N N O~
H
O N
N
H
Analogously, 100 mg (0.199 mmol) of ethyl { [4-{ [3-(Isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]amino}(oxo)acetate, 81.9 mg (0.398 mmol) of histidine methyl ester hydrochloride, 60.3 mg (0.597 mmol) of triethylamine and 0.2 mg (0.002 mmol) of DMAP in 2 ml of THF give 18 mg ( 14%) of methyl 2-{ [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy }-3,5-bis(trifluoromethyl)phenyl]amino } (oxo)-acetylamino-3-(4-imidazolyl)-propionate.

Le A 34 254-Foreign Countries 300 MHz'H-NMR (CDC13): 1.27, d, 6H; 3.05, sept, 1H; 3.16, dd, 1H; 3.30, dd, 1H;
3.74, s, 3H; 4.89, ddd, 1H; 6.72, dd, 1H; 6.84, d, 1H; 6.87, s, 1H; 6.94, d, 1H; 7.22, d, 1H; 7.67, s, 1H; 7.80, s, broad, 1H; 8.27, s, 2H; 9.12, s, broad, 1H; 9.43, s, broad, 1H.
Example 78 Dimethyl 2-(( f4-( f3-(isoproyyl)-1H-indol-5-ylloxyl-3,5-bis(trifluoromethyl~
phenyllamino ~ (oxo)acetylamino)-dimethylsuccinate O O
H
N N O~
F H O O~
O
Analogously, 100 mg (0.199 mmol) of ethyl { [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]amino}(oxo)acetate, 78.6 mg (0.398 mmol) of aspartic acid dimethyl ester hydrochlomde, 60.3 mg (0.597 mmol) of triethylamine and 0.2 mg (0.02 mmol) of DMAP in 2 ml of THF give 37 mg (30%) of dimethyl 2-2-({ [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy }-3,5-bis(trifluoromethyl)phenyl]-amino }
(oxo)acetylamino)dimethyl-succinate.
200 MHz 'H-NMR (DMSO): 1.19, d, 6H; 2.96, m, 2H; 3.20, m, 1H; 3.62, s, 3H;
3.68, s, 3H; 4.85, q, 1H; 6.63, dd, 1H; 6.72, d, 1H; 7.08, d, 1H; 7.23, d, 1H;
8.70, s, 2H; 9.48, d, broad, 1H; 10.73, d, broad, 1H; 11.48, s, 1H.

Le A 34 254-Foreign Countries Examule 79 ten-Butyl ~~4-(f3-(isopropyl)-1H-indol-5-ylloxy~-3,5-bis(trifluoro-methyl)phen amino ~ (oxo)acetate F FF
O I ~ O
H~F / N O
F F H O
S
At room temperature, a solution of 38.7 mg (0.235 mmol) of ten-butyl oxalyl chloride in 1 ml of dichloromethane is added to a solution of 100 mg (0.224 mmol) of 5-[4-amino-2,6-bis(trifluoro-methyl)phenoxy]-3-isopropyl-1H-indo1e and 45.3 mg (0.447 mmol) of triethylamine in 2 ml of dichloromethane, and the mixture is stirred for 5 h. Purification of the resulting crude product on silica gel (cyclohexane/ethyl acetate 5:1) gives 104 mg (88%) of tert-butyl { [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy }-3,S-bis(trifluoro-methyl)phenyl]amino } (oxo)acetate.
400 MHz ~H-NMR (CDC13): 1.27, d, 6H; 1.63, s, 9H; 3.05, sept, 1H; 6.73, dd, 1H;
6.84, d, 1 H; 6.94, d, 1 H; 7.22, d, 1 H; 7.80, s, broad, 1 H; 8.24, s, 2H;
9.08, s, broad, 1 H.

Le A 34 254-Forei~~n Countries Example 80 3-(2 5-Dimethyl)pentyl ( f4-~ f3-(isopro~yl)-1H-indol-5-ylloxyl-3.5-bis(trifluoro-methyl)phenyllamino 1 (oxo)acetate F
F F
\ O ~ \ O
O
H~F / H
F F O
In a similar manner, 100 mg (0.249 mmol) of 5-[4-amino-2,6-bis(trifluoro-methyl)phenoxy]-3-isopropyl-1H-indo1e, 45.3 mg (0.497 mmol) of triethylamine and 50.3 mg (0.261 mmol) of 3-[(2,5-dimethyl)pentyl] oxalyl chloride in 2 ml of dichloromethane give, after purification on silica gel (cyclohexane/methylene chloride 1:1), 120 mg (84%) of 3-(2,5-dimethyl)pentyl-{ [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoromethyl)phenyl]amino } (oxo)acetate.
200 MHz ~H-NMR (CDC13): 0.96, dd, 12H; 1.27, d, 6H; 2.10, oct, 2H; 3.05, sept, 4.79, t, 1H; 6.73, dd, 1H; 6.82, d, 1H; 6.94, d, 1H; 7.23, d, 1H; 7.81, s, broad, 1H;
8.29, s, 2H; 9.14, s, broad, 1H.
Example 81 2-Propyl ( f4-f f3-(isopropyl)-1H-indol-5-ylloxyl-3 5-bis(trifluoro-methyl)phenyll-amino ) (oxo)acetate F F
O ~ \ O
O
H ~F / H
F F O

Le A 34 254-Foreign Countries In a similar manner, 100 mg (0.224 mmol) of 5-[4-amino-2,6-bis(trifluoro-methyl)phenoxy]-3-isopropyl-1H-indo1e, 45.3 mg (0.447 mmol) of triethylamine and 35.4 mg (0.235 mmol) of isopropyl oxalyl chloride in 2 ml of dichloromethane give, after purification on silica gel (cyclohexane/ethyl acetate 5:1), 10 mg (9%) of 2-propyl { [4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoromethyl)phenyl]-amino } (oxo)acetate.
200 MHz 'H-NMR (DMSO): 1.18, d, 12H; 1.34, d, 6H; 2.97, sept, 1H; 3.05, sept, 5.12, sept, 1H; 6.63, dd, 1H; 6.72, d, 1H; 6.94, d, 1H; 7.08, d, 1H; 7.26, d, 1H; 8.61, s, 2H; 10.74, d, broad, 1H; 11.38, s, broad, 1H.
Example 82 2-Benzyloxy-N-(4-1 f3-(isopropel)-1H-indol-5-ylloxyl-3,5-bis(trifluoro-meth~phenyllacetamide \ O /
N ~ /' O
F H
F F
In a similar manner, 200 mg (0.497 mmol) of 5-[4-amino-2,6-bis(trifluoro-methyl)phenoxy]-3-isopropyl-1H-indo1e, 75.4 mg (0.746 mmol) of triethylamine and 96.4 mg (0.522 mmol) of benzyloxyacetyl chloride in 4 ml of dichloromethane give, after purification on silica gel (cyclohexane/methylene chloride 1:1), 200 mg (73%) of 2-benzyloxy-N-[4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3>5-bis(trifluoro-methyl)-phenyl]acetamide.
300 MHz ~H-NMR (CDC13): 1.27, d, 6H; 3.05, sept, 1H; 4.15> s, 2H; 4.70, s, 2H;
6.72, dd, 1H; 6.83, d, 1H; 6.93, d, 1H; 7.21, d, 1H; 7.40, m, SH; 7.79, s, broad, 1H;
8.14, s, 2H; 8.50, s, broad, 1H.

Le A 34 254-Foreicn Countries Example 83 2-Hydroxy -N-f4-( f3-(isopropyl)-1H-indol-5-yllox bis(trifluoromethyl)phenyllacetamide F
F F
O
N~OH
H F F H
A solution of 166 mg (0.302 mmol) of 2-benzyloxy-N-[4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro-methyl)phenyl]acetamide in 10 ml of ethanol is admixed with Pd/C (10%) and hydrogenated overnight with hydrogen. The catalyst is filtered off through kieselguhr and the solvent is removed under reduced pressure, giving 130 mg (94%) of 2-hydroxy-N-[4-{ [3-(isopropyl)-1H-indol-5-yl]oxy}-3,S
bis(trifluoro-methyl)phenyl]acetamide.
200 MHz 'H-NMR (DMSO): 1.18, d, 6H; 2.96, sept, 1H; 4.08, d, 2H; 5.89, t, 1H;
6.62, dd, 1H; 6.68, d, 1H; 7.06, d, 1H; 7.23, d, 1H; 8.62, s, 2H; 10.45, s, broad, 1H;
10.73, s, broad, 1H.
Example 84 I(3,5-Dibromo-4-~ f3-(4-fluorobenzyl)-1H-indol-5-l~~r}phenyl)aminol(oxo)acetic acid Le A 34 254-Forei ~n Countries 20 mg (0.03 mmol) of ethyl [(3,5-dibromo-4-{ [3-(4-fluorobenzyl)-1H-indol-5-yl]oxy}phenyl)amino](oxo)acetate in 0.4 ml of 1N NaOH and 1 ml of dioxane are stirred at room temperature for 3.5 h. The mixture is acidified to pH 4 and extracted with ethyl acetate, the extract is dried over sodium sulphate and the solvent is removed under reduced pressure. This gives 18 mg (93%) of [(3,5-dibromo-4-{ [3-(4-fluorobenzyl)-1H-indol-5-yl]oxy}phenyl)amino](oxo)acetic acid.
Example 85 Ethyl (d3,5-dibromo-4-f(3-hexyl-1H-indol-5-yl)ox~[phenyl?amino)(oxo)acetate Br O
H~ Br ~ H O
O
62 mg (0.13 mmol) of 3,5-dibromo-4-[(3-hexyl-1H-indol-5-yl)oxyJaniline and mg of triethylamine are dissolved in 2 ml of dichloromethane and admixed dropwise with 25 mg (0.18 mmol) of ethyl oxalyl chloride. The reaction mixture is shaken with sat. NaHC03 solution, the aqueous phase is extracted lx with ethyl 15 acetate and the combined organic phases are washed Ix with sat. NaCI
solution, dried and concentrated using a rotary evaporator. Chromatography (cyclohexane/ethyl acetate = 20:1) gives 37 mg (50%) of ethyl ({3,5-dibromo-4-[(3-hexyl-1H-indol-yl)oxy]phenyl } amino)(oxo)acetate.
300 MHz 1H-NMR (CDC13): 0.88, m, 5H; 1.30, m, 4H; 1.46, t, 3H; 1.65, m, 2H;
2.63, t, 2H; 4.46, quart, 2H; 6.80, dd, 1H; 6.90, d, 1H; 6.98, m, 1H; 7.26, d, 1H; 7.83, s, broad, 1 H; 7.97, s, 2H; 8.87, s, broad, 1 H.

Le A 34 254-Foreign Countries ' ' - 16I -Example 86 Ethyl ((3 S-dibromo-4-( (3-(cyclohexylmeth~l)-1H-indol-5-ylloxy}phenyl)-aminol-(oxo)acetate N / O~
H
S In a similar manner, 122 mg (0.2SS mmol) of 3,S-dibromo-4-{ [3-(cyclohexylmethyl)-1H-indol-S-yl]oxy}aniline gives 51 mg (3S%) of ethyl [(3,S-dibromo-4-{[3-(cyclohexyl methyl)-1 H-indol-S-yl]oxy } phenyl)aminoJ(oxo)acetate.
300 MHz 'H-NMR (CDC13): 0.95, m, 2H; 1.18, m, 4H; 1,45, t, 3H; 1.68, m, SH;
2.52, d, 2H; 4.46, quart, 2H; 6.78, dd, 1H; 6.92, m, 2H; 7.23, d, 1H; 7.86, s, broad, 1H; 7.98, s, 2H; 8.88, s, broad, 1H.
Example 87 Ethyl t (4-( (3-(cyclohex 1y methyl)-1H-indol-S-ylloxy?-3,S-bis(trifluoromethyl)-1 S phenyllamino 1 (oxo)acetate N ~F

In a similar manner, 2S3 mg (O.SS mmol) of 4-{[3-(cyclohexylmethyl)-1H-indol-S-yl]oxy}-3,S-bis(trifluoromethyl)aniline give 162 mg (48%) of ethyl { [4-{ [3-(cyclohexylmethyl)-1H-indol-S-yl]oxy }-3,S-bis(trifluoromethyl)phenyl]amino }-(oxo)acetate.

Le A 34 254-Forei ~n Countries 300 MHz 1H-NMR (CDC13): 0.92, m, 2H; 1.18, m, 4H; 1.48, t, 3H; 1.63, m, SH;
2.50, d, 2H; 4.46, quart, 2H; 6.71, dd, 1H; 6.80, d, 1H; 6.95, m, 1H; 7.19, m, 1H;
7.83, s, 1H; 8.27, s, 2H; 9.09, s, 1H.
Example 88 Ethyl ( ( 3 5-dibromo-4-f (3-pentyl-1H-indol-5-yl)oxylphenyl ~
amino)(oxo)acetate Br O ( ~ O
H~ Br O
In a similar manner, 25 mg (0.06 mmol) of 3,5-dibromo-4-[(3-pentyl-1H-indot-5-yl)oxy]aniline give 30 mg (99%) of ethyl ({3,5-dibromo-4-((3-pentyl-1H-indol-5-yl)oxy]phenyl } amino)(oxo)acetate.
300 MHz 1H-NMR (CDC13): 0.88, m, SH; 1.31, m, 4H; 1.45, t, 3H; 1.65, m, 2H;
2.62, t, 2H; 4.45, quart, 2H; 6.80, dd, 1 H; 7.89, d, 1 H; 6.98, m, 1 H; 7.23, m; 7.83, s, broad, 1H; 7.97, s, 2H; 8.88, s, broad, IH.

Le A 34 254-Foreign Countries Example 89 Ethyl oxo( (4-((3-pentyl-IH-indol-5-yl)oxyl-3,5-bis(tr7fluoromethyl)-phenyll-amino~,acetate ~\
~F

In a similar manner, 38.8 mg (0.09 mmol) of 4-[(3-pentyl-1H-indol-5-yl)oxy]-3,5-bis(trifluoromethyl)aniline give 32 mg (66%) of ethyl oxo{ [4-[(3-pentyl-1H-indol-5-yl)oxy)-3,5-bis(trifluoro-methyl)phenyl]amino}acetate.
300 MHz 'H-NMR (CDCl3): 0.88, m, 5H; 1.31, m, 4H; 1.47, t, 3H; 1.62, m, 2H;
2.60, t, 2H; 4.46, quart, 2H; 6.73, dd, 1H; 6.81, d, 1H; 6.97, m, 1H; 7.22, d, 1H; 7.81, s, 1H; 8.24, s, 2H; 9.11, s, IH.
Example 90 Ethyl ( ( 3,5-dibromo-4-((3-butyl-IH-indol-5-yl~oxy~henyl f amino)(oxo)acetate Br O I \ O
H~ Br ~ H ~\/~
O
In a similar manner, 72 mg (0.14 mmol) of 3,5-dibromo-4-[(3-butyl-1H-indol-5-yl)oxy]aniline give 68 mg (82%) of ethyl ({3,5-dibromo-4-[(3-butyl-IH-indol-5-yl)oxy]phenyl } amino)(oxo)acetate.

Le A 34 254-Foreign Countries 300 MHz'H-NMR (CDCl3): 0.92, t, 3H; 1.35, m, 2H; 1.45, t, 3H; 1.63, m, 2H;
2.63, t, 2H; 4.45, quart, 2H; 6.78, dd, 1H; 6.91, d, 1H; 6.99, m, 1H; 7.23, d, 1H;
7.83, s, IH; 7.98, s, 2H; 8.86, s, IH.
Example 91 Ethyl (f4-f~,3-butyl-1H-indol-5-yl)oxyl-3,5-bis(trifluorometh~phenyllaminof-(oxo~
acetate ~\
~F
H
In a similar manner, 44 mg (0.11 mmol) of 4-[(3-butyl-1H-indol-5-yl)oxy]-3,5-bis(trifluoromethyl)aniline give 49 mg (77%) of ethyl { [4-[(3-butyl-1H-indol-yl)oxy]-3>5-bis(trifluoromethyl)-phenyl]-amino } (oxo)acetate.
300 MHz'H-NMR (CDC13): 0.90, t, 3H; 1.30, m, 2H; 1.47, t, 3H; 1.61, m, 2H;
2.61, t, 2H; 4.48, quart, 2H; 6.72, dd, 1H; 6.8, d, 1H; 6.97, m, 1H; 7.21, m, 1H;
7.83, s, 1H; 8.28, s, 2H; 9.10, s, 1H.
Example 92 Ethyl ((3,5-dibromo-4-f(3-propyl-1H-indol-5-yl)oxy~phen_,.yllamino)(oxo)acetate Br O ~ \ O
H~ Br r H Ow/
O

Ix A 34 254-Foreign Countries In a similar manner, 185 mg (0.44 mmol) of 3,5-dibromo-4-[(3-propyl-1H-indol-5-yl)oxyJaniline give II4 mg (41%) of ethyl ({3,5-dibromo-4-[(3-propyl-1H-indol-yl)oxy]phenyl } amino)(oxo)acetate.
200 MHz 'H-NMR (CDC13): 0.96, t, 3H; 1.45, t, 3H; 1.67, m, 2H; 2.6I, t, 2H;
4.46, quart, 2H; 6.79, dd, IH; 6.90, d, 1H; 6.98, d, 1H; 7.20, m, 1H; 7.82, s, IH;
7.96, s, 2H; 8.86, s, IH.
Example 93 Ethyl (13,5-dibromo-4-f(3-methyl-1H-indol-5-girl)oxylphenyl)amino)(oxo)acetate Br O
i I ~ o O
H Br H~ ~./
IO
In a similar manner, 650 mg (1.64 mmol) of 3,5-dibromo-4-[(3-methyl-1H-indol-5-yI)oxyJaniline give 520 mg (60%) of ethyl ({3,5-dibromo-4-[(3-methyl-1H-indol-yl)oxy]phenyl } amino)-(oxo)acetate.
300 MHz 'H-NMR (CDC13): 1.45, t, 3H; 2.25, s, 3H; 4.45, quart, 2H; 6.82, m, 2H;
6.96, d, 1H; 7.26, d, 1H; 7.81, s, 1H; 7.98, s, 2H; 8.88, s, 1H.
Example 94 Ethyl ( ( 3,5-dimethyl-4-((3-propyl-IH-indol-5-yl)oxy]phenyl }
amino)(oxo)acetate O I ~ O
H~ / N Ow/
H
O

Le A 34 254-Foreig_rt Countries In a similar manner, 120 mg (0.41mmo1) of 3,5-dimethyl-4-[(3-propyl-1H-indol-5-yl)oxyJaniline give 157 mg (97%) of ethyl ({3,5-dimethyl-4-[(3-propyl-1H-indol-yl)oxy]phenyl } amino)-(oxo)acetate.
300 MHz'H-NMR (CDCl3): 0.95, t, 3H; 1.43, t, 3H; 1.62, m, 2H; 2.15, s, 6H;
2.59, t, 2H; 4.41, quart, 2H; 6.86, m, 2H; 6.95, d, 1H; 7.21, d, 1H; 7.40, s, 2H;
7.8I, s, IH;
8.81, s, 1H.
Example 95 tert-ButYI ({4-f(3-isopropyl-1H-indol-5=yl)oxyl-3,5-dimethtrlphenyl?amino)(oxo)-acetate v In a similar manner, 200 mg (0.679 mmol) of 4-[(3-isopropyl-IH-indol-5-yl)oxy]-3,5-dimethylaniline and I51 mg (0.917 mmol) of tert-butyl oxalyl chloride give 188 mg (65%) of tent-butyl ({4-[(3-isopropyl-1H-indol-5-yl)oxy]-3,5-dimethyl-phenyl } amino)(oxo)acetate.
300 MHz'H-NMR (CDCl3): 1.27, d, 6H; 1.61, s, 9H; 2.17, s, 6H; 3.05, m, IH;
6.73, dd, 1H; 6.86, d, 1H; 6.94, d, 1H; 7.21, d, 1H; 7.39, s, 2H; 7.78, s, 1H; 8.78, s, 1H.

Le A 34 254-Foreign Countries Example 96 Isopropyl ( 4-((3-isopropyl-1H-indol-5-yl)oxyl-3,5-dimethylphenyllamino)(oxo)-acetate In a similar manner, 200 mg (0.679 mmol) of 4-[(3-isopropyl-1H-indol-5-yl)oxy]-3,5-dimethylaniline and 138 mg (0.917 mmol) of isopropyl oxalyl chloride give 247 mg (89%) of isopropyl ({4-[(3-isopropyl-1H-indol-S-yl)oxy]-3,5-dimethyl-phenyl } amino)(oxo)acetate.
300 MHz ' H-NMR (CDCl3): 1.27, d, 6H; 1.41, d, 6H; 2.18, s, 6H; 3.05, m, 1 H;
5.21, m, 1H; 6.72, dd, 1H; 6.86, d, IH; 6.93, d, 1H; 7.21, d, 1H; 7.40, s, 2H; 7.79, s, 1H;
8.80, s, 1 H.
Example 97 2-HydroxyethYl ((4-1(3-(4-fiuorobenz~)-1H-indol-5-ylloxyl-3,5-bis(trifluoro-meth~l),phen llaminol(oxo)-acetate F
OH
Under argon, 5 mg of sodium are dissolved in ethanediol. 65 mg (0.11 mmol) of ethyl { [4-{ [3-(4-fluorobenzyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoromethyl)phenyl]-amino}(oxo)acetate are added and the reaction mixture is stirred at room temperature Lx A 34 254-Foreit~ Countries for 3 h and then poured into water. The mixture is extracted with dichloromethane and dried over sodium sulphate, and the solvent is removed under reduced pressure.
Chromatographic purification (cyclohexane/ethyl acetate = 1:1) gives 15 mg (22%) of 2-hydroxyethyl { [4-{ [3-(4-fluorobenzyl)-1H-indol-5-yl]oxy}-3,5-bis(trifluoro methyl)phenyl]amino}(oxo)-acetate.
300 MHz ~H-NMR (CDC13): 3.95, s, 2H; 4.03, t, 2H; 4.51, t, 2H; 6.41, d, 1H;
6.80, dd, 1H; 6.90, m, 2H; 7.12, m, 2H; 7.23, m, 1H; 7.90, s, 1H; 8.21, s, 2H; 9.14, s, 1H.
The examples below are prepared similarly to the examples above, and in accordance with the general description of the process.

Le A 34 254-Foreien Countries Example No.
0 0~
F F O
N
\F / N N Ow O \ I O H O
F F
F

O H
O ~ N
HN ~ ~ / N \\
H O

O H
O ~' N
HN
~OH

O
~ O N~O
O
HN
/ H~ _ O
O N~OH
O ~( HN / ~ ~ N 11 H O

N~o HN
/ H O HO

' O ~ ~ N OH
H N / ~ ' / N \\
H OHO

Le A 34 254-Foreign Countries Example No.
o \
\ O 1 N
hiN / ~ ' / N ll H O

O
O N O
HN ~( O
O ~ O~ N OH
H N / ~ \ / N \\
H O

O
O N~O
\ O '(~\ ~( HN , / N
H O

HO O
\ O ~ O\\ (~H~.~NF'1z H N ~ / N \, H O

\ O ~ O N~OH
HN / \ / N
H O

Ho 0 0 ~ ~
\ O ~ ~~~~NH
HN ~
/ H~ O_ 'O

Le A 34 254-Foreign Countries Example No.

° , ° ,~ off HN / ' / N
H O
NH=

o ~
H ~~~~
I ~ N O

F F
F /
O ~ O w HN ~ F ~ / N
F H O
F

~ I ~~ H
N N
H
115 °
F
F F
\ O
N [ / I /
H F F F H
O

F F
F
O N / F\
O H F H

/ ~ i o / ~ I o \I
N H
H O

Ix A 34 254-Foreign Countries Example No.
/ ~ ° ~ o N I / I / N II O
H H
O

/ ~ ° ~ o I / I I H~O~Oi O

/ w o w o N I / I / N O
H H

F F
~F
\ o \ o N I /F I / N \
H H
F F /

F F
~F
/ ~ O I \ O
N~ / N
H F H
F F

/ I ° i ( o F
N
H H F F

Le A 34 254-Forei.~n Countries Example No.
F F
'F
\ ° \ o p ~ H \
F F I /
CI

F F
~F
\ o \ o I / I
H F N
H
F F \

F F
~F
\ ° \ o IN1 F ~ / N \
F~F H

F F
~F
\ o \ o N~/ ~/ /
H F v _N
F H
F

F F
'F
\ ° I \ o F
/ \
H F N
H
F

Le A 34 254-Forei;?n Countries Example No.
F F
~F
\ O \ O
N / ~ N \
H F H
F I / /

F F
~F
I \ ° I \ o H~ / N I \
F H
F /
CI

F
F F
\ ° \ o N I / F I / N \
H F H
F /

F
F F
\ ° ~ o N I / I / \ F
H F v _N
H
F F I /

F F
~F
I \ ° I \ o N~ /
H F N
F H
F

Le A 34 254-Foreign Countries Example No.
F F
~F
I \ ° I \ o / /
H~ H
F F O

F F
~F
\ ° I \ °
/ N /
H
FF S

F F
F
\ ° \ o CI
H I /F I / H / I
F F \
CI

F F _ °/
F
\ ° \ ° I \
H I F I / H
N /
F F

F F
~F
I \ ° I \ o I \ °\
F / /
H F N
H
F

F F
~F
I \ ° I \ o H~ / / CI
~% N
H
F F \
CI

Le A 34 254-Forei~~n Countries Example No.
F F
~F
\ ° \ O
N l / ~ ~ _ ,-H F N
H
FF \

F F
~F
\ ° I \ O
/ N
H F H
F F

F F
~F
/ I ~ ° I ~ o / N \
H
F F I / /

F F
~F
I \ ° I \ o H~J / \
N
F H
F /
F

F F
F ~ ~ F
° I \ ° / CI
N'~ /
H F F H ~~~N
F O

Le A 34 254-Foreign Countries Example No.
F F
~F
O ~ \ O
F H
N~ /
F /

F F
~F
\ ° I \ o N~ /
H
F F H
F

F F
~F
\ ° ~ \ O
N~ /
H F
F F

F F
~F
\ ° \ O
N ( /
H F F
F

F F
~F
\ ° \ o /
H F V N
F H
F

F F
O F
\ \ O CI
/ / N O
F
F ~ O ~ ~ O
i 51 c1 Le A 34 254-Forei:;n Countries - 1?$ -Example No.
F F
~F
\ ° \ o N I / I /
H F v _N
F H
F \ ( F
CI F F

F F
~F
O I \ O CI
H'~\%F / N / I
H
FF \

F F
~F
\ ° \ o N I ~ I / / F
H N
F H
FF \
F
F

F F F
\ O \ O I
H F I / N /
H
FF \

F F
~F
\ O I \ O
F N
H
F F O
I

Le A 34 254-Foreign Countries Example No.
F F
~F
\ O \ O
H F
F F /

F F
~F
I \ ° I \ O / I °\
-''\~ / N \
H F H
F F

F F
~F
I \ ° I \ o H
F F I /

F F
~F
\ o \ o I/
H N
F F H
160 F Br L.e A 34 254-Foreign Countries Example No.
F F
~F
\ O ~ \ O
N- V /
H F N
H
F F

\ o I \ o N~ /
H
H

\ o I \ o N~ /
H N
H

F F
~F
\ O ~ \ O
V F / N ~ \
H
F F /
O~

Le A 34 254-Forei Qn Countries Exam 1e No.
F F
~F
/I°I\ o H~ /
F H

/I ° /~ o F
N ~ N
H H F F

F F
~F
\ ° \ O
p / H \
F F

F F _ F
\ ° \ o H F N
H
F F

F F
~F
I \ ° I \ o H~ / N I \
F H
F /

F F
~F
I \ ° I \ o N
/ /
F H
F
/ I
17~ \

Le A 34 254-Foreign Countries Exam 1e No.
F F
~F
\ ° I \ o ~ ~~ F
N~ / \
H F N
H
F

F F
~F
\ O \ O
I / I /
H F N \
H
F F / /

F F
~F
\ ~ \ o F F I
CI

F
F F
\ ~ \ o F
H I F I / N I \
H
F /

F
F F
\ o \ o N I / ~ / \ F
H F v _N
H
F F I

F F
~F
\ ° \ O
/
~N
H F v H
F F

L.e A 34 254-Foreign Countries Exam 1e No.
F F
~F
/ \ ° \ o I/
~N
H F v H
F F

F F
~F
\ ° \ o N
H F N
FF H

F F
~F
\ ° ~ \ o a H F / H / I
F F
179 cf F F
F O
\ ° \ O \
N I F I / N I /
H H
F F
18~
F F
F
\ ° \ O \ °\
N I / F I / I /
H F
F

F F
~F
I \ ° I \ o / .~ / a H F N
F H
F
182 a Le A 34 254-Foreign Countries Exam 1e No.
F F
~F
\ O \ O
N / / N /
H F H I
F F \

F F
F
\ O \ O
N I / I / N
H F H
F F

F F
~F
\ o \ o I / H \ \
F F I / /

F F
~F
\ O \ O
/ /
N F
F F /
F
F F

F F \ F
F I
O O i I \ CI
/ /
w H F F H ~ ~N
F O

I,e A 34 254-Foreign Countries Exam 1e No.
F F
'F
\ o \ o N I / I /
H N
F F H
F /
\
CI

F F
~F
/ \ o \ o N I / I /
F F H
F

F F
~F
\ o \ o I / I /
H F N
H
F F

F F
'F
o \ o N /
H N
F F H

F F
'F
/ \ ° ~ o I / I /
H F N
F H
F

F F
F
/ \ o \ o ci N / / N O
H F F H
F ~ ~ O

Le A 34 254-Foreign Countries Exam 1e No.
F F
'F
\ O \ O
N ~ / / /
H F N
F F H \ F
CI F F

F F
~F
\ O \ O CI
/
H F N /
H
FF \
F

F F
~F
\ ° \ o N ~ / ~ , / F
H
F
FF \
F
F

F F F
\ O \ O CI
H F / N /
F F H \
197 °
F F
'F
\ O \ O
/
H F
F F O
'~'~~/

Le A 34 254-Foreign Countries Exam 1e No.
F F
'F
\ O \ O
/ H \
H F
F F /

F F
~F
/ \ O \ O / O\
H I F I / N \
H

F F
'F
I \ ° ( \ o N / / \
H F N
F H
F . /

F F
'F
/ I \ o I \ o N / /
H N
F
202 F F e, F F
'F
\ ° \ O
r /
H F N
H
F F

Le A 34 254-Foreign Countries Exam 1e No.

N~ I r H
H

N I / ( /
H N
H

Claims (16)

Claims

1. Compounds of the general formula (I) in which Z represents O, S, CH2, CHF or CF2, R1 and R2 are identical or different and represent hydrogen, halogen, (C1-C6)-alkyl, CF3, CHF2, CH2F, vinyl or (C3-C7)-cycloalkyl, where at least one of the two substituents is not hydrogen and is located in the position ortho to the bridge bond, R3 represents a head group with an optionally derivatized carboxyl radical, R4 and R5 are identical or different and each represents hydrogen, hydroxyl, halogen, cyano, nitro, (C1-C4)-alkyl, or the radical of the formula NR18R19, where R18 and R19 are identical or different and each represents hydrogen, phenyl, benzyl, (C1-C6)-alkyl, (C1-C6)-alkoxy or (C3-C8)-cycloalkyl, which for their part are optionally mono- or polysubstituted by halogen, hydroxyl, amino, (C1-C4)-alkoxy, -CO-O(C1-C4)-alkyl, -NH-CO-O(C1-C4)-alkyl, O-CO-(C1-C4)-alkyl, by a heterocycle or by optionally halogen- or hydroxyl-substituted phenyl, R6 represents halogen or represents hydrogen, hydroxyl, OR10, NR11R12, (C1-C8)-alkyl, (C3-C8)-cycloalkyl, (C6-C10)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to four identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned radicals are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C6)-alkyl, optionally R23-substituted (C1-C6)-alkoxy, (C3-C8)-cycloalkyl, -OCO-R13, -CO-O-R14, -CO-NR15R16, -NHCOR17 and -NHCOOR17, where R10, R11, R12, R13, R14, R15, R16, R17 and R23 are identical or different and each represents hydrogen, phenyl, benzyl, (C1-C6)-alkyl, (C1-C6)-alkoxy or (C3-C8)-cycloalkyl which for their part are optionally mono- or polysubstituted by halogen, hydroxyl, amino, (C1-C4)-alkoxy, -CO-O(C1-C4)-alkyl, -NH-CO-O(C1-C4)-alkyl, -O-CO-(C1-C4)-alkyl, by a heterocycle or by optionally halogen- or hydroxyl-substituted phenyl, or represents the radical in which R20 and R21 together with the carbon atom to which they are attached form a carbonyl group, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C1-C6)-alkyl, (C1-C6)-alkoxy or the radical -NR15R16 and R22 represents hydrogen, hydroxyl, OR10, NR11R12, (C1-C8)-alkyl, (C3-C8)-cycloalkyl, (C6-C10)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to four identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned radicals are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C6)-alkyl, optionally R23-substituted (C1-C6)-alkoxy, (C3-C8)-cycloalkyl, -OCO-R13, -CO-O-R14, -CO-NR15R16, -NHCOR17 and -NHCOOR17, where R10, R11, R12, R13, R14, R15, R16, R17 and R23 are identical or different and each represents hydrogen, phenyl, benzyl, (C1-C6)-alkyl, (C1-C6)-alkoxy or (C3-C8)-cycloalkyl which for their part are optionally mono- or polysubstituted by halogen, hydroxyl, amino, (C1-C4)-alkoxy, -CO-O(C1-C4)-alkyl, -NH-CO-O(C1-C4)-alkyl, -O-CO-(C1-C4)-alkyl, by a heterocycle or by optionally halogen- or hydroxyl-substituted phenyl, R7 represents hydrogen or represents an acyl group which can be cleaved off under physiological conditions forming an NH function, preferably represents hydrogen or acetyl, and their salts.

2. Compounds of the general formula (I) according to Claim 1 in which Z represents O, S, CH2, CHF or CF2, R1 and R2 are identical or different and represent hydrogen, halogen, (C1-C6)-alkyl, CF3, CHF2, CH2F, vinyl or (C3-C7)-cycloalkyl, where at least one of the two substituents is not hydrogen and is located in the position ortho to the bridge bond, R3 represents a head group of the formula A-(CH2)n-(CO)m-R8, in which A represents CH2, O, S, CO or represents NR9, in which R9 represents hydrogen, (C1-C6)-alkyl or (C3-C8)-cycloalkyl, or represents the group -(CH2)n-(CO)m,-O-(C1-C4)-alkyl, n represents a number from 0 to 3, m represents 1 or 2, R8 represents hydrogen, hydroxyl, OR10, NR11R12, (C1-C8)-alkyl, (C3-C8)-cycloalkyl, (C6-C10)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to four identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned radicals are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C6)-alkyl, optionally R23-substituted (C1-C6)-alkoxy, (C3-C8)-cycloalkyl, -OCO-R13, -CO-O-R14, -CO-NR15R16, -NHCOR17 and -NHCOOR17, where R10, R11, R12, R13, R14, R15, R16, R17 and R23 are identical or different and each represents hydrogen, phenyl, benzyl, (C1-C6)-alkyl, (C1-C6)-alkoxy or (C3-C8)-cycloalkyl which for their part are optionally mono- or potysubstituted by halogen, hydroxyl, amino, (C1-C4)-alkoxy, -CO-O(C1-C4)-alkyl, -NH-CO-O(C1-C4)-alkyl, -O-CO-(C1-C4)-alkyl, by a heterocycle or by optionally halogen- or hydroxyl-substituted phenyl, R4 and R5 are identical or different and each represents hydrogen, hydroxyl, halogen, cyano, nitro, (C1-C4)-alkyl, or the radical of the formula NR18R19, where R18 and R19 have the meanings given for R10 and can be identical to or different from this substituent, R6 represents halogen or has the meaning given for R8 and is identical to or different from this substituent or represents the radical in which R20 and R21 together with the carbon atom to which they are attached form a carbonyl group, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C1-C6)-alkyl, (C1-C6)-alkoxy or the radical -NR15R16 and R22 has the meaning of R8 and is identical to or different from this substituent, R7 represents hydrogen or represents an acyl group which can be cleaved off under physiological conditions forming an NH function, preferably represents hydrogen or acetyl, and their salts.

3. Compounds of the general formula (I) according to Claim 1, in which Z represents O, CH2 or CF2, R1 and R2 are identical or different and represent hydrogen, fluorine, chlorine, bromine, (C1-C4)-alkyl, CF3, CHF2, CH2F, vinyl or (C3-C6)-cycloalkyl, where at least one of the two substituents is not hydrogen and is located in the position ortho to the bridge bond, R3 represents a head group with an optionally derivatized carboxyl radical, of the formula A-(CH2)n-(CO)m-R8, in which A represents CH2, O or represents NR9, in which R9 represents hydrogen, (C1-C4)-alkyl or (C3-C7)-cycloalkyl, or represents the group (CH2)n-(CO)m-O-(C1-C4)-alkyl, n represents the number 0 or 1, m represents the number 1 or 2, R8 represents hydrogen, hydroxyl, OR10, NR11R12-, (C1-C8)-alkyl, (C3-C8)-cycloalkyl, (C6-C10)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to four identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-alkoxyphenyl, (C3-C8)-cycloalkyl, -O-CO-R13, -CO-O-R14, -CO-NR15R16, -NHCOR17 and -NHCOOR17, where R10, R11, R12, R13, R14, R15, R16 and R17 are identical or different and each represents hydrogen, benzyl, (C1-C6)-alkyl or (C3-C8)-cycloalkyl which for their part are optionally mono- or polysubstituted by fluorine, chlorine, hydroxyl, amino, -CO-O(C1-C4)-alkyl, -NH-CO-O(C1-C4)-alkyl, -O-CO-(C1-C4)-alkyl, imidazolyl, hydroxyphenyl or (C1-C4)-alkoxy, R4 and R5 are identical or different and each represents hydrogen, halogen or (C1-C4)-alkyl, R6 represents chlorine, fluorine, bromine or has the meaning given for R8 and is identical to or different from this above substituent or represents the radical in which R20 and R21 together with the carbon atom to which they are attached form a carbonyl group, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C1-C4)-alkyl, (C1-C4)-alkoxy or the radical-NR15R16 and R22 has the meaning of R8 and is identical to or different from this substituent, R7 represents hydrogen, and their salts.

4. Compounds of the general formula (I) according to Claim 1, in which Z represents CH2 or represents oxygen, R1 and R2 are identical or different and represent methyl, ethyl, propyl, isopropyl, chlorine, bromine, CF3, vinyl or cyclopropyl, where both substituents are located in the position ortho to the bridge bond, R3 represents the group -O-(CH2)n-CO-R8 or represents the group NR9-(CH2)n-(CO)m-R8, which is in each case located in the position para to the bridge bond, where R9 represents -CH2-CO-O-(C1-C4)-alkyl-substituted (C1-C4)-alkyl, (C3-C7)-cycloalkyl, -CO-CO-O-(C1-C4)-alkyl or hydrogen, m represents the number 1 or, in particular, 2, n represents the number 1 or 0, R8 represents methyl, ethyl, n-propyl, isopropyl, n-, i-, s- or t-butyl, n-pentyl or n-hexyl, thiophenyl, pyridyl or represents the groups -CH2-O-benzyl, OR10 or NR11R12, where R10 represents hydrogen or optionally hydroxyl-substituted straight-chain or branched alkyl having up to 7 carbon atoms, where R11 and R12 are identical or different and represent hydrogen, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, methoxy, ethoxy, n-propoxy, isopropoxy, t-butoxy, n-pentoxy, n-hexoxy or straight-chain or branched alkyl having up to 6 carbon atoms, where alkyl for its pan is optionally mono- or polysubstituted by identical or different substituents from the group consisting of hydroxyl, -CO-O(C1-C4)-alkyl, -NH-CO-O(C1-C4)-alkyl, imidazolyl and hydroxyphenyl, R4 and R5 represent methyl, fluorine or chlorine or hydrogen, R6 represents hydrogen, hydroxyl, OR10, NR11R12, methyl, ethyl, n-propyl, isopropyl, n-, i-, s- or t-butyl, (C3-C6)-cycloalkyl, (C6-C10)-aryl, or represents a saturated, unsaturated or aromatic S- to 10-membered heterocycle having up to three identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C3-C8)-cycloalkyl, O-CO-R13, -CO-O-R14, -CO-NR15R16 and -NHCOOR17, where R10, R11, R12, R13 R14, R15, R16 and R17 are identical or different and each represents hydrogen, benzyl, (C1-C4)-alkyl or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (C1-C4)-alkoxy, or represents the radical in which R20 and R21 together with the carbon atom to which they are attached form a carbonyl group, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C1-C4)-alkyl, (C1-C4)-alkoxy or the radical -NR15R16 and R22 represents hydrogen, hydroxyl, OR10, NR11R12, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C6-C10)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to three identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C3-C8)-cycloalkyl, O-CO-R13, -CO-O-R14, -CO-NR15R16 and -NHCOOR17 where R10, R11, R12, R13, R14, R15, R16 and R17, are identical or different and each represents hydrogen, benzyl, (C1-C4)-alkyl or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (C1-C4)-alkoxy, R7 represents hydrogen, and their salts.

5. Compounds of the general formula (I) in which Z represents O, S, CH2, CHF or CF2, R1 and R2 are identical or different and represent hydrogen, halogen, (C1-C6)-alkyl, CF3, CHF2, CH2F, vinyl or (C3-C7)-cycloalkyl, where at least one of the two substituents is not hydrogen and is located in the position ortho to the bridge bond, R3 represents a head group with optionally derivatized carboxyl radical, preferably represents a group of the formula A-(CH2)n-(CO)m-R8, in which A represents CH2, O, S, CO or represents NR9, in which R9 represents hydrogen, (C1-C6)-alkyl or (C3-C8)-cycloalkyl, n represents a number from 0 to 3, m represents 1 or 2, R8 represents hydrogen, hydroxyl, OR10, NR11R12, (C1-C8)-alkyl, (C3-C8)-cycloalkyl, (C6-C10)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to four identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C6)-alkyl, (C1-C6)-alkoxy, (C3-C8)-cycloalkyl, OCO-R13, -CO-O-R14, CO-NR15R16 and -NHCOOR17, where R10, R11, R12, R13, R14, R15, R16 and R17 are identical or different and each represents hydrogen, benzyl, (C1-C6)-alkyl or (C3-C8)-cycloalkyl which for their part are optionally substituted by amino or (C1-C4)-alkoxy, R4 and R5 are identical or different and each represents hydrogen, hydroxyl, halogen, cyano, nitro, (C1-C4)-alkyl or the radical of the formula NR18R19, where R18 and R19 have the meaning given for R10 and can be identical to or different from this substituent, R6 has the meaning given for R8 and is identical to or different from this substituent or represents the radical in which R20 and R21 together represent oxygen, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C1-C6)-alkyl, (C1-C6)-alkoxy or the radical -NR15R16 and R22 has the meaning of R8 and is identical to or different from this substituent, R7 represents hydrogen or represents an acyl group which can be cleaved off under physiological conditions forming an NH function, preferably represents hydrogen or acetyl, and their salts.

6. Compounds of the formula (I) according to Claim 5, in which Z represents O, CH2 or CF2, R1 and R2 are identical or different and represent hydrogen, fluorine, chlorine, bromine, (C1-C4)-alkyl, CF3, CHF2, CH2F, vinyl or (C3-C6)-cycloalkyl, where at least one of the two substituents is not hydrogen and is located in the position ortho to the bridge bond, where in particular both substituents are not hydrogen and both are located in the ortho position, R3 represents a head group with optionally derivatized carboxyl radical, preferably represents a group of the formula A-(CH2)n-(CO)m-R8, which is located in the position para to the bridge bond, in which A represents CH2, O or represents NR9, in which R9 represents hydrogen, (C1-C4)-alkyl or (C3-C7)-cycloalkyl, n represents 0 or 1, m represents 1 or 2, R8 represents hydrogen, hydroxyl, OR10, NR11R12, (C1-C6)-alkyl, (C3-C8)-cycloalkyl, (C6-C10)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to four identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C3-C8)-cycloalkyl, O-CO-R13, -CO-O-R14, -CO-NR15R16 and -NHCOOR17, where R10, R11, R12, R13, R14, R15, R16 and R17 are identical or different and each represents hydrogen, benzyl, (C1-C4)-alkyl or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (C1-C4)-alkoxy, R4 and R5 are identical or different and each represents hydrogen, halogen or (C1-C4)-alkyl, R6 has the meaning given for R8 and is identical to or different from this above substituent or represents the radical in which R20 and R21 together represent oxygen, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C1-C4)-alkyl, (C1-C4)-alkoxy or the radical -NR15R16 and R22 has the meaning of R8 and is identical to or different from this substituent, R7 represents hydrogen, and their salts.

7. Compounds of the formula (I) according to Claim 5, in which Z represents oxygen or CH2, R1 and R2 are identical or different and represent methyl, ethyl, propyl, isopropyl, chlorine, bromine, CF3, vinyl or cyclopropyl, where both substituents are located in the position ortho to the bridge bond, R3 represents the group -NR9-(CO)m-R8 or the group -O-(CH2)n-CO-R8, in each case in the position para to the bridge bond, where R9 represents hydrogen, (C1-C4)-alkyl or (C3-C7)-cycloalkyl, m represents 2, n represents 1, R8 represents (C1-C6)-alkyl, pyridyl, OR10 or NR11R12, where R10, R11 and R12 represent hydrogen, benzyl, (C1-C4)-alkyl or (C3-C6)-cycloalkyl, R4 and R5 represent hydrogen, methyl, fluorine or chlorine, R6 represents hydrogen, hydroxyl, OR10, NR11R12, (C1-C6)-alkyl, (C3-C6)-cycloalkyl, (C6-C10)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to three identical or different heteroatoms from the group consisting of S, O and N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C3-C8)-cycloalkyl, O-CO-R13, -CO-O-R14, -CO-NR15R16 and -NHCOOR17, where R10, R11, R12, R13, R14, R15, R16 and R17 are identical or different and each represents hydrogen, benzyl, (C1-C4)-alkyl or (C3-C6)-cycloalkyl which for their pan are optionally substituted by amino or (C1-C4)-alkoxy, or represents the radical in which R20 and R21 together represent oxygen, or are in each case identical or different and represent hydrogen, halogen, hydroxyl, (C1-C4)-alkyl, (C1-C4)-alkoxy or the radical -NR15R16 and R22 represents hydrogen, hydroxyl, OR10, NR11R12, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C6-C10)-aryl, or represents a saturated, unsaturated or aromatic 5- to 10-membered heterocycle having up to three identical or different heteroatoms from the group consisting of S, O and/or N, where the abovementioned hydrocarbon radicals and heterocycles are optionally substituted by one, two or three identical or different substituents from the group consisting of halogen, hydroxyl, cyano, nitro, amino, CF3, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C3-C8)-cycloalkyl, O-CO-R13, -CO-O-R14, -CO-NR15R16 and -NHCOOR17, where R10, R11, R12, R13, R14, R15, R16 and R17 are identical or different and each represents hydrogen, benzyl, (C1-C4)-alkyl or (C3-C6)-cycloalkyl which for their part are optionally substituted by amino or (C1-C4)-alkoxy, R7 represents hydrogen, and their salts.

8. Process for preparing compounds of the general formula (I) as defined in Claim 1, characterized in that reactive indole derivatives of the general formula (II) are reacted with reactive phenyl derivatives of the general formula (III) where the substituents R1, R2, R3, R4, R5, R6 and R7 have the meanings given in Claim 1 and R3' has the meaning given for R3 or represents NO2, NH2 or NPG, where PG represents a protective group, X and Y are in each case groups of opposite reactivity, Z' has the meaning given for Z or represents , 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).

9. Compounds of the formula (IV) in which R1, R2, R4, R5, R6 and R7 have the meanings given in Claim 1, Z' has the meaning given for Z in Claim 1 or represents CHOH, and R3' has the meaning given for R3 in Claim 1 or represents NO2, NH2 or NPG, with the proviso that if Z' represents CH2 R3' does not represent NO2, and that if Z' represents CH2, R3' represents NH2, R1 and R2 represent (C1-C4)-alkyl, R4 and R5 represent H and R6 represents amino-substituted (C3-C6)-cycloalkyl, R7 does not represent hydrogen.

10. Medicament, comprising at least one compound of the general formula (I) according to at least one of Claims 1 to 8.

11. Process for preparing medicaments, characterized in that at least one compound of the general formula (I) according to at least one of Claims 1 to 8 is converted with auxiliaries and excipients into a suitable administration form.

12. Use of the compounds of the general formula (I) according to at least one of Claims 1 to 8 for controlling diseases.

13. Use of compounds of the general formula (I) according to at least one of Claims 1 to 8 for the treatment and/or prophylaxis of arteriosclerosis and hypercholesterolaemia.

14. Use of compounds of the general formula (I) according to at least one of Claims 1 to 8 for preparing medicaments for the prophylaxis and/or treatment of disease forms which can be treated with natural thyroid hormone.

15. Use of compounds of the general formula (I) according to at least one of Claims 12 to 14 in combination with other medicaments.

16. Medicament, comprising at least one compound of the general formula (17 according to at least one of Claims 1 to 8 and excipients, auxiliaries, solvents, vehicles, emulsifiers and/or dispersants.