MX2008009918A - Trialkylsilylbenzylaminocarboxyindoles, indazoles and indolines and their use in treating cetp-mediated disorders - Google Patents

Abstract

Compounds of formula (I) their manufacture, pharmaceutical compositions containing them and their use as medicaments in the treatment and /or prophylaxis of diseases mediated by cholesteryl ester transfer protein (CETP).

Description

- - TRIALQUILSILILBENCILAMINOCARBOXIINDOLES, INDAZOLES AND INDOLINAS AND THEIR USE IN THE TREATMENT OF MEDIATED DISORDERS BY CETP DESCRIPTION OF THE INVENTION The present invention relates to new lH-indole-7-carboxamido, lH-indazole-7-carboxamido and lH-indoline-7-carboxamido derivatives, to their preparation, to pharmaceutical compositions containing them and to their use as medicines. In a first aspect, the present invention relates to a compound of the formula I (I) where -XY- is -CRa = CRc- or -CRa = N- or -CRaRb-CRcRd-, in which Ra, Rb, Rc and Rd are independently chosen from the group consisting of hydrogen and Ci-C8 alkyl; R1, R2, R4 and R5 are independently selected from the group consisting of hydrogen, Ci-Cs alkyl, Ci-Cg alkoxy, halogen and halo-Ci-Cs alkyl; No. Ref .: 195115 s Si (Ci-C6 alkyl) 3; it is selected from the group consisting of hydrogen and Ci-C8 alkyl; it is selected from the group consisting of hydrogen, Ci-C8 alkyl, hydroxy and halogen; is selected from the group consisting of Ci-Cg alkyl, C2-C8 alkenyl, halogen-Ci-C8 alkyl, heterocyclyl, heteroaryl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-alkoxy -C8, halogen-Ci-Cg alkyl, halo-Ci-C8 alkoxy and halogen, phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halogen-Ci alkyl -C8, halogen-Ci-C8 alkoxy and halogen, -0R12, in which R12 is Ci-Cg alkyl or phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-alkoxy C8, halogen-Ci-C8 alkyl, halogen-Ci-C8 alkoxy and halogen, -NR13R14, wherein R13 and R14 are independently selected from hydrogen, Ci-C8 alkyl, and phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halo-Ci-C8 alkyl, halo-Ci-C8 alkoxy and - - halogen, and -C (0) -OR, wherein R is hydrogen or Ci-C8 alkyl; R9, R10 and R11 independently of each other are selected from the group consisting of hydrogen, Ci-C8 alkyl, cycloalkyl, Ci-C8 alkoxy, halogen-Ci-C8 alkyl and halogen; n is the number 1, 2 or 3; and all its pharmaceutically acceptable salts. In another embodiment, the present invention relates to a compound of the formula I, wherein -XY- is -CRa = CRc- or -CRa = N- or -CRaRb-CRcRd-, wherein Ra, Rb, Rc and Rd are independently selected from the group consisting of hydrogen and Ci-C8 alkyl; R1, R2, R4 and R5 are independently selected from the group consisting of hydrogen, Ci-C8 alkyl, Cx-Cs alkoxy, halogen and halo-Ci-C8 alkyl; R3 is Si (Ci-C6 alkyl) 3; R6 is selected from the group consisting of hydrogen and Ci-C8 alkyl; R7 is selected from the group consisting of hydrogen, Ci-C8 alkyl, hydroxy and halogen; R8 is selected from the group consisting of Ci-C8 alkyl, C2-C8 alkenyl, halo-Ci-C8 alkyl, heterocyclyl, heteroaryl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halo-Ci-C8 alkyl, halo-Ci-C8 alkoxy and halogen, phenyl, which is substituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halogen-Ci-C8 alkyl, halogen-Ci-C8 alkoxy and halogen, -0R12, wherein R12 is Ci-C8 alkyl or phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halo-Ci-C8 alkyl, halo-Ci-C8 alkoxy and halogen, -NR13R14, wherein R 13 and R 14 independently from each other are selected from hydrogen, C 1 -C 8 alkyl, and phenyl, which is unsubstituted or substituted by one or two groups independently chosen from C 1 -C 8 alkyl, C 1 -C 8 alkoxy, C 1 -C 6 haloalkyl C8, halogen-Ci-C8 alkoxy and halogen, and -C (0) -OR15, wherein R15 is hydrogen or Ci-C8 alkyl; 0 and R11 independently of each other are selected from the group consisting of hydrogen, Ci-C8 alkyl, C3-C8 cycloalkyl, Ci-C8 alkoxy, haloC1-C8 alkyl, and halogen; it is number 1, 2 or 3; - - and all pharmaceutically acceptable salts thereof. Unless indicated otherwise, the following definitions are established to illustrate and define the meaning and scope of the various terms that are used to describe the present invention. The term "Ci-C8 alkyl", alone or in combination, means a straight or branched chain alkyl radical, of 1 to 8 carbon atoms, eg a straight or branched chain alkyl radical having from 1 to 6 carbon atoms. carbon, eg a straight or branched chain alkyl moiety of 1 to 4 carbon atoms. Examples of straight-chain or branched C 1 -C 8 alkyl radicals are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl isomers, hexyl isomers, heptyl isomers and octyl isomers, eg methyl, ethyl and tert-butyl. The term "C2-8 alkenyl", alone or in combination, means a straight or branched chain hydrocarbon radical containing an olefinic bond and up to 8 carbon atoms, eg, up to 6, eg, up to 4 carbon atoms. Examples of alkenyl moieties are ethenyl, 1-propenyl, 2-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl and isobutenyl. The term "cycloalkyl" or "C3-7 cycloalkyl" denotes a saturated carbocyclic moiety, having from 3 to 7 carbon atoms, for example cyclopropyl, cyclobutyl, - - cyclopentyl, cyclohexyl or cycloheptyl. Cyclopropyl, cyclobutyl and cyclopentyl are especially preferred.

The term "alkoxy" means the radical R'-O-, wherein R 'is Ci-C8 alkyl and the term "Ci-C8 alkyl" has the meaning defined above. Examples of Ci-Ce alkoxy radicals are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy, preferably methoxy and ethoxy and with special preference methoxy. The term "(Ci-8 alkoxy) Ci-8 alkyl" means Ci-C8 alkyl moieties as defined above, in which at least one of the hydrogen atoms of the Ci-C8 alkyl moiety has been replaced by an alkoxy group , preferably methoxy or ethoxy. Among the preferred lower alkyl-alkoxy radicals are 2-methoxyethyl, 3-methoxypropyl or 1-methoxy-1-methyl-ethyl. The term "halogen" means fluorine, chlorine, bromine or iodine. The term "haloalkyl Ci_8 alkyl" means C1-C8 alkyl radicals defined above, in which at least one of the hydrogen atoms of the Ci-C8 alkyl radical has been replaced by a halogen atom, eg fluorine or chlorine. Examples of halogenated Ci ~ C8 alkyl groups include trifluoromethyl, difluoromethyl, fluomethyl and chlorodifluoromethyl. The term "halogenoalkoxy Ci_g" means alkoxy moieties - - Ci-Ce already defined above, in which at least one of the hydrogen atoms of the Ci-C8 alkoxy moiety is substituted by a halogen atom, preferably fluorine or chlorine. Among the preferred halogenated Ci-C8 alkoxy groups are trifluoromethoxy, difluoromethoxy, fluormetoxy and chlorodifluoromethoxy. The term "(Ci_8 alkoxy) -halogenoalkyl Ci_8" means halogen-Ci-C8 alkyl moieties as defined above, in which at least one of the hydrogen atoms of the halogen-Ci-C8 alkyl moiety has been replaced by an alkoxy moiety . An example of a moiety (Ci-C8 alkoxy) -halogen-Ci-C8 alkyl is 2,2,2-trifluoro-l-methoxy-1-trifluoromethyl-ethyl. The term "heteroaryl" means a 5- or 6-membered aromatic ring, containing one, two or three atoms chosen from nitrogen, oxygen and / or sulfur. Examples of heteroaryl radicals are furyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, thienyl, isoxazolyl, thiazolyl, isothiazolyl, oxazolyl, imidazolyl or pyrrolyl, eg furyl, thienyl, thiazolyl and pyridyl. The term "heterocyclyl" means a 5- or 6-membered ring, saturated or partially unsaturated, containing one, two or three atoms chosen from nitrogen, oxygen and sulfur. Examples of heterocyclyl include piperidinyl, piperazinyl, azepinyl, pyrrolidinyl, pyrazolidinyl, imidazolinyl, imidazolidinyl, pyridinyl, pyridazinyl, pyrimidinyl, oxazolidinyl, isoxazolidinyl, morpholinyl, thiazolidinyl, isothiazolidinyl, thiadiazolylidinyl, dihydrofuryl, tetrahydrofuryl, dihydropyranyl, tetrahydropyranyl, tetrahydrothiopyranyl and thiamorpholinyl, eg tetrahydrothiopyranyl. The term "pharmaceutically acceptable salts" means those salts which retain the efficacy and biological properties of free bases or free acids and which are not annoying in any biological sense or in any other. The salts are formed with inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, preferably with hydrochloric acid, and with organic acids, such as acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, N-acetylcysteine and similar. In addition, these salts can be obtained by the addition of an inorganic base or an organic base on a free acid. Salts derived from an inorganic base include, but are not limited to: the sodium, potassium, lithium, ammonium, calcium, magnesium and the like salts. Salts derived from organic bases include, but are not limited to: the salts of amines - ¬ primary, secondary and tertiary, of substituted amines, including substituted amines of natural origin, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, ethanolamine, lysine, arginine, N- ethylpiperidine, piperidine, polyimine resins and the like. The compound of the formula I can also be present in the form of z itterion. The compounds of the formula I can also be present in solvated form, eg hydrated. The solvation can take place in the course of the production process or can take place, for example, as a consequence of the hygroscopic properties of an initially anhydrous compound of the formula I (hydration). The term "pharmaceutically acceptable salts" also includes physiologically acceptable solvates. "Isomers" are compounds that have identical molecular formulas, but that differ in the nature or binding order of their atoms or in the arrangement of their atoms in space. The isomers that differ in the arrangement of their atoms in space are called "stereoisomers." Stereoisomers that are not mirror images of each other are termed "diastereomers" and stereoisomers are mirror images that can not overlap are termed "enantiomers" or sometimes - - optical isomers. A carbon atom attached to four non-identical substituents is termed a "chiral center". In one embodiment, the present invention provides a compound of formula I, wherein -XY- means -CRa = CRc- and Ra and Rc are independently selected from the group consisting of hydrogen and Ci-Cs alkyl. In another embodiment, the present invention provides a compound of formula I, wherein -XY- means -CRa = CRc- and Ra and R ° are hydrogen. In one embodiment, the present invention provides compounds of formula I having the formula wherein Ra and Rc are independently selected from the group consisting of hydrogen and Ci-Cs alkyl; R1, R2, R4 and R5 are independently selected from the group consisting of hydrogen, Ci-Cs alkyl, CI-CB alkoxy, halogen and halo-Ci-Cs alkyl; R3 is Si (Ci-C6 alkyl) 3; R6 is selected from the group consisting of hydrogen and Ci ~ C8 alkyl; - - is selected from the group consisting of hydrogen, Ci-C8 alkyl, hydroxy and halogen; is selected from the group consisting of Ci-Cg alkyl, C2-C8 alkenyl, halogen-Ci-C8 alkyl, heterocyclyl, heteroaryl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkylalkoxy Ci-Cs, halogeno-Ci-C8 alkyl, halogeno-Ci-C8 alkoxy and halogen, phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halogen -alkyl Ci-C8, halogeno-alkoxy Ci-Cg and halogen, -0R12, in which R12 is Ci-C8 alkyl or phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, C 1 -C 8 alkoxy, C 1 -C 8 halogenoalkyl, C 1 -C 8 halogenoalkoxy and halogen, -NR 13 R 14, wherein R 13 and R 14 are independently selected from hydrogen, Ci-C 8 alkyl, and phenyl, which is substituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halogen-Ci-C8 alkyl, halo-Ci-C8 alkoxy and halogen, and -C (0) -OR15, wherein R15 is hydrogen or Ci-C8 alkyl; 0 and R11 regardless of whether they are chosen between - - the group consisting of hydrogen, Ci-C8 alkyl, C3-C8 cycloalkyl, Ci-C8 alkoxy, halogeno-Ci-Ce alkyl, and halogen; n is the number 1, 2 or 3; and all its pharmaceutically acceptable salts. In another embodiment, the invention further provides compounds of the formula I, wherein -X-Y- is -CRa = N- and Ra is hydrogen or Ci-C8 alkyl; thus indicating that compounds of formula I that have the formula (I-B) wherein Ra is hydrogen or Ci-C8 alkyl; R1, R2, R4 and R5 are independently selected from the group consisting of hydrogen, Ci-C8 alkyl, Ci-C8 alkoxy, halogen and halo-Ci-C8 alkyl; R3 is Si (C1-C6 alkyl) 3; R6 is selected from the group consisting of hydrogen and Ci-C8 alkyl; R7 is selected from the group consisting of hydrogen, - Ci-C8 alkyl, hydroxy and halogen; is selected from the group consisting of Ci-C8 alkyl, C2-C8 alkenyl, haloC1-C8 alkyl, heterocyclyl, heteroaryl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-alkoxy -C8, halogen-Ci-C8 alkyl, halogen-Ci-C8 alkoxy and halogen, phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halogen-Ci alkyl -C8, halogeno-Ci-C8 alkoxy and halogen, -0R12, in which R12 is Ci-C8 alkyl or phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-alkoxy C8, halogen-Ci-C8 alkyl, halogen-Ci-C8 alkoxy and halogen, -NR13R14, wherein R13 and R14 independently of each other are selected from hydrogen, Ci-C8 alkyl, and phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halo-Ci-C8 alkyl, halo-Ci-C8 alkoxy and halogen , and -C (0) -OR15, wherein R15 is hydrogen or Ci-C8 alkyl; 0 and R11 independently of each other are selected from the group consisting of hydrogen, Ci ~ C8 alkyl, C3-C8 cycloalkyl, Ci-C8 alkoxy, halogen-alkyl i-Cs, and halogen; n is the number 1, 2 or 3; and all its pharmaceutically acceptable salts. In one embodiment, the present invention provides a compound of formula I-B, wherein Ra is hydrogen. In addition, the invention relates to compounds of formula I, wherein -XY- means -CRaRb-CRcRd- and Ra, Rb, Rc and Rd are independently chosen from the group consisting of hydrogen and Ci-C8 alkyl; thus, it means compounds of the formula I which have the formula wherein Ra, Rb, Rc and Rd are independently selected from the group consisting of hydrogen and Ci-C8 alkyl; R1, R2, R4 and R5 are independently selected from the group consisting of hydrogen, Ci-C8 alkyl, Ci-C8 alkoxy, halogen and haloC1-C8 alkyl; R3 is Si (Ci-C6 alkyl) 3; it is selected from the group consisting of hydrogen and Ci-C8 alkyl; it is selected from the group consisting of hydrogen, Ci-C8 alkyl, hydroxy and halogen; is selected from the group consisting of Ci-C8 alkyl, C2-C8 alkenyl, halogen-Ci-C8 alkyl, heterocyclyl, heteroaryl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-alkoxy -C8, halogen-Ci-C8 alkyl, halogen-Ci-C8 alkoxy and halogen, phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halogen-Ci alkyl -C8, halogen-Ci-C8 alkoxy and halogen, -0R12, in which R12 is Ci-C8 alkyl or phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-alkoxy C8, halogen-Ci-C8 alkyl, halogen-Ci-C8 alkoxy and halogen, -NR13R14, wherein R13 and R14 are independently selected from hydrogen, Ci-C8 alkyl, and phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halo-Ci-C8 alkyl, halo-Ci-C8 alkoxy and halogen , and -C (0) -OR15, wherein R15 is hydrogen or - Ci-C8 alkyl; R9, R10 and R11 independently of each other are selected from the group consisting of hydrogen, Ci-C8 alkyl, cycloalkyl, Ci-Ca alkoxy, halo-Ci-C8 alkyl and halogen; n is the number 1, 2 or 3; and all its pharmaceutically acceptable salts. In one embodiment, the present invention provides compounds of the formula I-C, wherein Ra, Rb, Rc and Rd are hydrogen. In another embodiment, the present invention provides a compound of formula I, wherein R 1, R 2, R 4 and R 5 are hydrogen. In still another embodiment, the present invention provides compounds of formula I, wherein R 1 is Ci-C8 alkoxy or halogen and R 2, R 4 and R 5 are hydrogen. In still another embodiment, the present invention provides compounds of the formula I, wherein R 2 is halogen and R 1, R 4 and R 5 are hydrogen. In one embodiment, the present invention provides compounds of the formula I, wherein R3 is Si (CH3) 3 or Si (CH3) 2CH (CH3) 2 · In still another embodiment, the present invention provides compounds of the formula I, wherein R3 is Si (CH3) 3. In one embodiment, the present invention provides compounds, wherein R6 is hydrogen.

In one embodiment, the present invention provides compounds of the formula I, wherein R7 is hydrogen. In another embodiment, the present invention provides compounds of the formula I, wherein R8 is selected from the group consisting of Ci-C8 alkyl, C2-C8 alkenyl and halo-Ci-C8 alkyl. In yet another embodiment, the present invention provides compounds of the formula I, wherein R 8 is heterocyclyl or heteroaryl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-Cg alkyl, Ci-C8 alkoxy, halogen Ci-C8 alkyl, halogen-Ci-C8 alkoxy and halogen. In yet another embodiment, the present invention provides compounds of the formula I, wherein heterocyclyl is tetrahydrothiopyranyl and heteroaryl is selected from furanyl, pyridyl, thiazolyl and thienyl. In one embodiment, the present invention provides compounds of formula I, wherein R8 is -OR12 and R12 is Ci-C8 alkyl or phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl , Ci-C8 alkoxy, haloC1-C8 alkyl, haloC1-C8 alkoxy and halogen. In one embodiment, the present invention provides compounds of the formula I, wherein R8 is -NR13R14, wherein R13 and R14 are independently selected from hydrogen, Ci-C8 alkyl and phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-Cs alkyl, Ci-C8 alkoxy, halo-Ci-C8 alkyl, halo-alkoxy Ci-Cs and halogen. In one embodiment, the present invention provides compounds of the formula I, wherein R8 is -C (0) -OR15, wherein R15 is hydrogen or Ci-C8 alkyl. In another embodiment, the present invention provides compounds of the formula I, wherein R8 is phenyl, which is unsubstituted or substituted by one or two groups independently chosen from C1-C8 alkyl, Ci-C8 alkoxy, haloalkyl Ci -C8, halogen-Ci-C8 alkoxy and halogen. In yet another embodiment, the present invention provides compounds of the formula I-A, wherein R 8 is phenyl which is substituted by one or two groups independently chosen from halogen-C 1 -C 8 alkyl, halogen-C 1 -C 8 alkoxy and halogen. In yet another embodiment, the present invention provides compounds of the formula IA, wherein R8 is selected from 3-trifluoromethoxyphenyl, 3-trifluoromethyl, 3-chloro-4-fluomethyl, 4-fluoro-3-trifluoromethylphenyl, 3-difluoromethoxyphenyl and 3,4-dichlorophenyl. In still another embodiment, the present invention provides compounds of the formula I, wherein R8 is selected from 3-trifluoromethoxyphenyl, 3-trifluoromethyl, 3-chloro-4-fluomethyl, 4-fluoro-3-trifluoromethylphenyl, 3-difluoromethoxyphenyl, 3-trifluoromethylphenyl and 3,4-dichlorophenyl. In still another embodiment, the present invention provides compounds of formula I, wherein R is 3-trifluoromethylphenyl. In another modality, the present invention provides compounds of the formula I, wherein at least one of R9, R10 and R11 is selected from the group consisting of Ci-C8 alkyl, halogen-Ci-Cs alkyl and halogen. In still another embodiment, the present invention provides compounds of the formula I, wherein one of R9, R10 and R11 is selected from halogen-Ci-C8 alkyl and halogen. In another embodiment, the present invention provides compounds of the formula I, wherein R10 is halogen. In still another embodiment, the present invention provides compounds of the formula I, wherein halogen means chlorine. In one embodiment, the present invention provides compounds of the formula I, wherein two of R9, R10 and R11 are halogen and the other is hydrogen. In another embodiment, the present invention provides compounds of the formula I, wherein R9 and R10 are halogen and R11 is hydrogen. In still another embodiment, the present invention provides compounds of the formula I, wherein R9 is fluorine, R10 is chlorine and R11 is hydrogen. The integer n is 1 or 2. In one embodiment, the present invention provides compounds of formula I, wherein n is 1. On the other hand, pharmaceutically acceptable salts of The compounds of the formula I and the pharmaceutically acceptable esters of the compounds of the formula I also constitute, individually, embodiments of the present invention. The compounds of the formula I can form addition salts with acids, for example with conventional pharmaceutically acceptable acids, eg the hydrochloride, hydrobromide, phosphate, acetate, fumarate, maleate, salicylate, sulfate, pyruvate, citrate, lactate salts , mandelate, tartrate and methanesulfonate. The hydrochloride salts are preferred. Solvates and hydrates of the compounds of the formula I and their salts are also part of the present invention. The compounds of the formula I can contain various asymmetric centers and can be present in the form of pure enantiomers, mixtures of enantiomers, for example, racemates, optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates or mixtures of diastereomeric racemates. The optically active forms can be obtained, for example, by resolution of the racemates, by asymmetric synthesis or by asymmetric chromatography (chromatography with an adsorbent or a chiral eluent). The invention encompasses all these forms. It will be noted that the compounds of the general formula I of this invention can be derivatized in their functional groups to obtain derivatives capable of being converted from new "in vivo" in the original compound. The physiologically acceptable and metabolically labile derivatives capable of regenerating "in vivo" the original compounds of the general formula I are also within the scope of this invention. Another aspect of the present invention is the process for obtaining the compounds of the formula I already defined above, the process consists in a) reacting an acid of the formula II wherein -X-Y-, R9, R10 and R11 have the meanings defined above and R is hydrogen or Ci-Ce alkyl, with an amine of formula III wherein R1 to R8 and n have the meanings defined above, in the presence of a binding agent; or, alternatively, b) reacting a halogenated derivative of the formula IV (IV) in which -XY-, R9, R10 and R11 have the meanings defined above and Hal means halogen, with an amine of formula III, in the presence of a suitable catalyst and carbon monoxide and, if desired, convert the compound obtained in a pharmaceutically acceptable acid addition salt. Preferred binding agents are l-ethyl-3- (3-dimethyl-aminopropyl) -carbodiimide (EDC) or its hydrochloride (EDC-HC1), N, N'-dicyclohexyl-carbodiimide (DCC) or tetrafluoroborate O- (benzotriazol-1-yl) -?,?,? ' ,? ' -tetramethyl-uronium (TBTU). In more detail, the compounds of the formula I can be obtained by the methods described below, by the methods described in the examples or by similar methods. The appropriate reaction conditions for the individual steps are already known to those skilled in the art. The starting materials are commercial products, or can be obtained by methods similar to those described below, by methods described in the references cited in the text or in the examples or by methods known in the art. According to the reaction scheme 1, the compounds of the formula I can be obtained by linking an acid derivative II with an appropriate secondary amine derivative III. Reaction scheme 1 (II) (ni) (i) If the acids (R = H) of the formula II are used in this process, then standard binding reagents for peptides can be used to activate the acid before carrying out the binding reaction. For example, the acid derivative II (R = H) is mixed with a binding reagent, for example EDC or EDC-HC1, DCC or TBTU in an inert solvent, for example dimethylformamide (DMF), dimethylacetamide (DMA) or dichloromethane (DCM) together with the appropriate secondary amine derivative III. Optionally, a base (eg N, N-diisopropylethylamine, triethylamine, N-methyl-morpholine) and / or 1-hydroxybenzotriazole (HOBT) can be added. It shakes - - the reaction mixture at a temperature of -30 ° C to 70 ° C (preferably at room temperature) for a time of 1 to 24 h. Alternatively, the esters of the formula II (R = CH3 or C2H5) can be used in the binding process. In this case the amine derivative III is treated with trimethyl aluminum in an inert solvent, for example DCM or toluene, at room temperature, before carrying out the addition of the ester derivative II.

The acid derivatives of the formula II are commercial products or can be obtained according to the standard syntheses of indole, indoline or indazole, eg, in the manner described in the general schemes from 4 to 7. The possible routes for synthesizing the derivatives of amine III are represented in the general schemes from 8 to 11 or are described within the section of the examples. According to reaction scheme 2, the compounds of the general formula I can also be obtained by linking a halogenated derivative IV with an appropriate secondary amine derivative III in the presence of a suitable catalyst (eg Pd (dppf) Cl 2) and monoxide of carbon (eg from 1 to 100 atmospheres) in an inert solvent (preferably a mixture of methanol and toluene) at a temperature of 50 ° C to 150 ° C. The possible routes of synthesis of the necessary halogenated derivatives IV are described in general schemes 4, 5 and 9.

Reaction scheme 2 (IV) (III) (I) A possible synthesis of the compounds of the general formula I, in which R8 represents an OR12 group, is described in the general scheme 3. In a first step an acid derivative II is reacted with an amine derivative V applying standard peptide binding conditions (described in scheme 1). The etherification of the hydroxy group of intermediate VI to obtain the final compounds is carried out by standard methods (for example Mitsunobu reaction). If the appropriate substituents Ra and Rc of the compounds of the formula I, in which -XY- represents -CRa = CRc-, are not yet present in the acid derivative II or in the halogenated derivative IV which is used for the reaction of addition, the substituents may be introduced by transformation of a group -CH = CRC-, -CRa = CH- or -CH = CH- into -CRa = CRc- applying standard chemical synthesis. The compounds of the formula I, wherein -X-Y- means - - -CRaRb-CRcRd-, can be obtained using the appropriate derivative of acid II or the halogenated derivative IV in the reaction of binding with amine III or by transformation of a group -CRa = CRc- in -CRaRb-CRcRd- in any stage of the synthesis For example, this can be carried out with sodium borohydride in acetic acid. Reaction scheme 3 The compounds of the formula II and of the formula IV, wherein -X-Y- is -CH = CH-, can be obtained in the manner described in reaction schemes 4 and 5.

According to the reaction scheme 4, the compounds of the general formula VII can be converted into the indoles of the formula IVa in one step. Thus, the compounds of the formula VII are treated with an excess of a Grignard vinyl reagent (preferably 3 equivalents) at low temperature (preferably at or below -40 ° C) in tetrahydrofuran (THF) to obtain the bromo-indole compounds of the general structure IVa. Bromo-indoles IVa can become the - derivatives of acid lia by halogen-metal exchange reaction (preferably using reagents of alkyl lithium) and blocking the organometallic intermediate with a suitable electrophile, for example carbon dioxide or an alkyl chloroformate. The bromo-indoles IVa can also react with carbon monoxide (for example from 1 to 100 atmospheres) and an alcohol in the presence of a palladium catalyst (eg Pd (dppf) Cl2) to obtain the compounds of the invention. formula lia. Alternatively, the compounds of the formula IVa and lia can be obtained starting from anilines of the general structure VIII. By iodination of the compounds of the formula VIII (for example with iodine or N-iodosuccinimide) it is possible to obtain the iodo-anilines IX which can be converted into compounds of the formula X by applying the addition conditions of Sonogashira. In this way, the compounds of the formula IX are reacted with ethynyltrimethylsilane in the presence of a palladium catalyst (eg Pd (PPh3) 2C12), copper iodide (I) and an amine-type base, for example triethylamine. The acetylenes protected with trimethylsilyl X can first be deprotected (eg with tetrabutylammonium fluoride in THF) and then cyclized to give the compounds of the formula IVa or can be cyclized directly into the compounds of the formula IVa using of potassium tert-butoxide, in a polar solvent, for example the N- methylpyrrolidone (NMP). The compounds of the formulas lia and IVa can also be obtained starting from chloroacetophenone derivatives XI. For this purpose, the aniline VIII derivatives are treated with chloroacetonitrile in the presence of a mixture of boron trichloride and aluminum trichloride in an inert solvent to obtain the compounds of the formula XI which are then cyclized to obtain the IVa indoles with the intervention of sodium borohydride. in dioxane. Reaction scheme 5 XVI XV llb An alternative route for the synthesis of compounds of the formula II and formula IV, wherein -XY- is -CH = CH- and R9 is fluorine, is represented in the reaction scheme 5. The fluor-anilines XII can be converted into iodine compounds XIII (R = H) using an iodination reagent, for example N-iodosuccinimide. Alternatively, an appropriate protecting group R, for example an alkoxycarbonyl group, can be introduced onto the aniline nitrogen before carrying out the iodination step. The protecting group R can be introduced by treatment of a compound of the formula XII, in which R = H, with an appropriate alkyl chloroformate (for example methyl or ethyl chloroformate), in an inert solvent, in the presence of a base (eg sodium bicarbonate). The formation of acetylenes XIV is achieved by the Sonogashira reaction of the compounds of the formula XIII with ethynyltrimethylsilane. The compounds of the formula XIV, in which the protecting group R is an alkoxycarbonyl group, can be cyclized to obtain the indole XV derivatives by treatment with a base (for example NaOEt in ethanol) or a fluoride reagent, for example fluoride of tetrabutylammonium, in a solvent of the THF type. For the compounds of the formula XIV, wherein R is hydrogen, the cyclization which produces the indoles of the formula XV can be carried out using a base of the potassium tert-butoxide type in NMP. Alternatively, the trimethylsilyl protecting group can be removed from the acetylene radical before carrying out the cyclization (for example with tetrabutylammonium fluoride in THF). The characters of formula XV can also be synthesized from compounds of formula XVI. In In this case, the derivatives XVI are first treated with the dimethylacetal of the, -dimet il phormamide in the presence of a base (eg pyrrolidine) and in a second step with hydrogen in the presence of a suitable catalyst ( eg palladium on carbon) in a protic solvent, for example methanol. The characters of formula XV can also be obtained from aniline derivatives XII (R = H) by reaction with chloroacetonitrile in the presence of a mixture of boron trichloride and aluminum trichloride and subsequent cyclization using sodium borohydride in dioxane, similarly to the conversion of the aniline derivatives VIII into the compounds of the formula IV which is described in the reaction scheme 4. By treatment of the indoles of the formula XV with an excess of n -but i 1 - 1 itioy tert-butoxide Potassium at a low temperature (preferably below -70 ° C) achieves the formation of an organometallic intermediate compound that can react with e 1 rct, such as carbon dioxide or an alkyl chloroformate, to form the acid derivatives Ilb.

- - Reaction scheme 6 XX lie According to the reaction scheme 6, the indole derivatives of the formula II can be obtained, wherein -X-Y- is -CH = CRC-, starting from isatoic anhydride derivatives of the general formula XVII. For example, the compounds of the formula XVII can be converted firstly into anthranilic acid esters XVIII (eg with sodium methoxide or methanol in the presence of DMAP) and then into halogenated derivatives XIX by treatment with a halogenating agent, of the iodine type or N-iodosuccinimide. The compounds XIX can then be reacted with suitably substituted acetylenes (Sonogashira reaction) to obtain the compounds of the formula XX which are subsequently cyclized to give the indole derivatives. The cyclization step can be carried out - - using a base, for example potassium tert-butoxide, in a solvent of the NMP type or using palladium (II) chloride in a solvent of the acetonitrile type. The compounds of the formula lie, in which R = alkyl, can be converted into the corresponding acids (R = H) by treatment with an aqueous hydroxide (eg lithium or sodium hydroxide) in a polar solvent (preferably methanol and / or THF). Reaction scheme 7 fight The acid derivatives of the formula II, wherein -XY- is -CR12 = N-, can be synthesized in the manner described in the reaction scheme 7. The anilines XXI can be brominated to obtain compounds of the formula XXII which can be cyclized to obtain indazole XXIII derivatives by treatment with sodium nitrite in acetic acid.

- - The secondary amines of the general formula III can be synthesized by standard methods. They can be synthesized in the manner described in reaction schemes 8 to 11. Reaction scheme 8 In the reaction scheme 8 a possible synthesis of the compounds Illa (R6 = H) is illustrated either by reductive amination of benzaldehyde derivatives XXIV with amines XXV or by reductive amination of aldehydes XXVII with benzylamine derivatives XXVI. The necessary amines and starting aldehydes are commercially available or can be synthesized using standard methods, eg those described in the section on products. Alternatively, the secondary amines Illa can be synthesized from the amide derivatives XXIX or XXXII in the manner described in reaction scheme 9.

The amide derivatives of the formula XXIX are accessible by reaction of benzoic acid derivatives XXVIII with amines XXV, while the amides of the formula XXXII can be synthesized by reaction of benzylic amines XXVI with acids XXXI. This amide formation can be carried out using reagents and standard conditions (described in the scheme of - - reaction 1). The necessary amines and starting acids are commercial products or can be synthesized by applying standard conditions, described, for example, in the section of the examples. Alternatively, the amide derivatives of the formula XXIX can be obtained from compounds of the formula XXX, wherein X is a halogen atom or a triflate. In this case, the compounds of the formula XXX are treated with carbon monoxide in the presence of an amine derivative XXV and a suitable catalyst (for example Pd (OAc) 2 and dppf). Reaction scheme 10 XXXIII XXXV 'Ha The amines of the formula Illa can also be obtained by alkylation of amide derivatives XXXIV with benzyl halides XXXIII (X = C1, Br, I) and subsequent cleavage of the amide bond of the intermediates XXXV, as described in scheme 10. For example, the trifluoroacetamide derivatives XXXIV (R = CF3) can be reacted with a base, such as sodium hydride, and then with a benzyl halide XXXIII in an inert solvent of the DMF type to obtain the - - compounds of the formula XXXV (R = CF3). A possible route to remove the trifluoroacetyl group from the compounds of the formula XXXV (R = CF3) consists of the reaction with sodium borohydride in ethanol. Reaction scheme 11 XXXVI III Secondary amines III can also be synthesized from imines XXXVI by reaction with an alkyl lithium reagent R6Li (eg methyl lithium) in the presence of a Lewis acid, for example ethyl etherate of boron trifluoride. Imines XXXVI are accessible from aldehydes XXIV and amines XXV by standard methods. The following examples illustrate the invention. In general, the nomenclature used in this application is based on the AUTONOM ™ v program. 4.0, a computerized system of the Beilstein Institute for the generation of the systematic nomenclature of the IUPAC. EXAMPLE 1 Obtaining the [2- (3-trifluoromethoxy-phenyl) -ethyl] - (4-trimethylsilyl-benzyl) -amide of 5-chloro-6-fluoro-lH- - - Indole-7-carboxylic acid To a solution of 5-chloro-6-fluoro-lH-indole-7-carboxylic acid (64 mg, 0.3 mmole), (4-tert-butyl-benzyl) - [2- (3-trifluoromethoxy-phenyl) -ethyl] -amine (92 mg, 0.25 mmol) and N-methyl-morpholine (76 mg, 0.75 mmol) in DMF (3 ml) the HBTU (142 mg, 0.375 mmol) is added. After stirring the reaction mixture to t.amb. overnight, it is diluted with water and extracted twice with diethyl ether. The organic phases are combined, washed twice with a 1N aqueous solution of NaOH, twice with a 1N aqueous solution of HC1 and once with an aqueous sat. of NaCl, dried with sodium sulfate, filtered and concentrated in vacuo. The remaining oil is purified by preparative HPLC to obtain [2- (3-trifluoromethoxy-phenyl) -ethyl] - (4-trimethylsilyl-benzyl) -amide of 5-chloro-6-fluoro-lH-indole-7-acid. carboxylic acid (36 mg, 26%) as a white solid. MS (ISP) = 563.4 (M + H) +. Obtaining 5-chloro-6-fluoro-lH-indole-7-carboxylic acid. 4-Chloro-3-fluoro-phenylamine (10 g, 68.7 mmol) is dissolved in dichloromethane (38 ml) and treated with sodium bicarbonate ( 6.82 g, 72.1 mmol) in water (100 ml). It is added dropwise to t.amb. Methyl chloroformate (8 ml, 103.0 mmol) for a period of 25 min (temperature rises from 22 to 28 ° C). After shaking to t.amb. for 1.5 h the reaction mixture was diluted with dichloromethane (100 ml). After the - - separation, the organic phase is washed with an aqueous sat. NaCl (45 ml), dried over magnesium sulfate, filtered and diluted with hexane (140 ml). The dichloromethane is then removed in vacuo and the resulting suspension is filtered, yielding methyl (4-chloro-3-fluoro-phenyl) -carbamate (13 g, 92%) as a white powder. EM (El) = 203.1 () +. Dissolve methyl (4-chloro-3-fluoro-phenyl) -carbamate (5.34 g, 26.2 min) in acetonitrile (50 ml) and treat with N-iodosuccinimide (6.49 g, 28.9 mmol) and trifluoromethanesulfonic acid (0.23 g). mi, 2.6 mmol) under a nitrogen atmosphere and stirred at RT. during 3 hours. The reaction mixture is then poured into an aqueous sat. of sodium bicarbonate (50 ml) and extracted twice with ethyl acetate. The organic phases are combined, washed with an aqueous sat. of NaCl, dried over magnesium sulfate, filtered and concentrated in vacuo to obtain methyl (4-chloro-5-fluoro-2-iodo-phenyl) -carbamate (8.2 g, 95%) as a blue powder Dark. MS (El) = 328.9 (M) +. Pd (PPh3) 2Cl2 (153 mg, 0.22 mmol) and copper iodide (I) (42 mg, 0.22 mmol) are dissolved in triethylamine (40 ml) and kept at boiling under reflux under argon for 20 min. . The reaction mixture was cooled to 0 ° C and methyl (4-chloro-5-fluoro-2-iodo-phenyl) -carbamate (7.2 g, 21 mmol) was added. After shaking to t.amb. for 10 min, ethynyltrimethylsilane (3.45 ml, 24. 9 mmole) (exothermic reaction: the temperature rises from 18 to 33 ° C) and the reaction mixture is stirred at RT. for an hour. The reaction mixture was then poured into a 1N aqueous solution of HC1 (180 ml) and ice and extracted twice with ethyl acetate (180 ml). The organic phases are combined, washed with water and an aqueous sat. of NaCl, dried over magnesium sulfate, filtered and concentrated in vacuo to give the crude methyl (4-chloro-5-fluoro-2-trimethylsilanylethynyl-phenyl) -carbamate. The crude methyl (4-chloro-5-fluoro-2-trimethylsilanylethynyl-phenyl) -carbamate was dissolved (approx. 21 mmol) in THF (200 ml) and treated at RT. with tetrabutylammonium fluoride (43.3 ml, 1M in THF, 43.3 mmol). After shaking to t.amb. for 5 min, the reaction mixture was heated to reflux under an argon atmosphere for one hour. The reaction mixture was cooled to RT. and concentrates with emptiness. The resulting oil is treated with water (55 ml), stirred for 10 min and finally extracted twice with ethyl acetate (100 ml). The organic phases are combined, washed successively with a 1M aqueous solution of HC1 (50 ml), an aqueous sat. of sodium bicarbonate (50 ml), an aqueous sat. NaCl (50 ml) and finally dried with magnesium sulfate, filtered and concentrated in vacuo. The residue was stirred with hexane (200 ml) under reflux, cooled to 5 ° C and filtered, yielding 5-chloro-6-fluoro-lH-indole (3.15 g, 85%) in - - slightly brown solid form. MS (El) = 169.1 (M) +. The THF (35 mL) was cooled to -75 ° C under an argon atmosphere and a 1.6M solution of n-butyllithium in hexane (19.05 mL, 30.5 mmol) was added. A solution of 5-chloro-6-fluoro-1H-indole (2.35 g, 13.7 mmol) in THF (9 ml) is added dropwise over 15 min, maintaining the temperature between -70 and -75 ° C. After stirring at this temperature for a further 5 min, a solution of potassium tert-butylate (3.7 g) in THF (15 ml) was added over 10 min maintaining the temperature between -70 and -75 ° C. The brown solution is stirred for 2 hours at the same temperature and treated with a large excess of solid carbon dioxide. The temperature rises to 10 ° C for a period of 75 min and the reaction mixture is treated with water (30 ml). After separation of the organic phase, the aqueous phase is extracted twice with diethyl ether (20 ml), treated with a concentrated aqueous solution of HC1 until pH = 1. The suspension is filtered., wash the solid with water and dry with high vacuum. The residue is stirred with hexane / diethyl ether (9/1, 10 ml) for 15 min and filtered, washed with the same solvent mixture (5 ml), the solid is collected and dried under high vacuum, obtaining 5-chloro-6-fluoro-lH-indole-7-carboxylic acid (2.2 g, 75%) as a light brown solid. MS (ISP) = 212.2 (M-H) ~. Obtaining 4-trimethylsilanyl-benzaldehyde Dissolve l-bromo-4- (trimethylsilyl) benzene (1.15 g, mmole) in THF (30 ml) and cooled to -78 ° C. Under argon, a 1.6 M solution of n-butyllithium in hexane (3.13 ml, 5 mmol) is added dropwise keeping the temperature below -70 ° C. The clear colorless solution was stirred at -78 ° C for 15 min and DMF (1.16 mL, 15 mmol) was added rapidly. The reaction temperature rises to -68 ° C. The reaction mixture was stirred at -78 ° C for a further 15 min, the reaction was quenched with a 1N aqueous solution of HC1 and extracted twice with diethyl ether. The organic phases are combined, washed twice with water and once with an aqueous sat. of NaCl, dried over sodium sulfate, filtered and the solvent evaporated, yielding 4-trimethylsilanyl-benzaldehyde (920 mg, 100%) as a colorless oil. The product has a sufficient purity to be used directly in the next step. E (ISP) = 179.2 (M + H) +. NMR-H1 (CDC13, 300 MHz) d = 10.02 (s, 1H) 7.84 (d, 2H), 7.69 (d, 2H), 0.31 (s, 9H). Obtaining [2- (3-trifluoromethoxy-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) -amine (3-trifluoromethoxy-phenyl) -acetonitrile is dissolved (10.4 g, 52 mmol) in THF (83 mL) and cooled to 0 ° C under nitrogen atmosphere. A 1M solution of the borane-THF complex in THF (274 ml, 274 mmol) was added dropwise over 55 min, maintaining the temperature between 0 and 2 ° C. After the addition is complete, the reaction mixture is stirred at t. - - amb. for 45 min more and heating at reflux for 17 h. The reaction mixture was cooled to 0 ° C and treated at 2 to 5 ° C with methanol (62 ml) over a period of 30 min. After refluxing for 1 h, the reaction mixture was concentrated in vacuo, the remaining residue was dissolved in methylene chloride and the mixture was extracted twice with a 1N aqueous solution of HC1. The aqueous phases are combined, treated with a concentrated aqueous NaOH solution to adjust the pH to 12 and extracted twice with methylene chloride. The organic phases are combined, washed with water, dried with magnesium sulfate, filtered and concentrated in vacuo to obtain a colorless oil (8.6 g). This oil is dissolved in diethyl ether (200 ml), treated with a 2.6N solution of HC1 in diethyl ether (20 ml), stirred at RT. for 1 h more, it is filtered, washed with diethyl ether and dried under vacuum, obtaining 2- (3-trifluoromethoxy-phenyl) -ethylamine hydrochloride. (2.34 g, 65%) as a white solid. MS (ISP) = 206.1 (M + H) +. The 4-trimethylsilanyl-benzaldehyde (178 mg, 1 mmol), the hydrochloride of 2- (3-trifluoromethoxy-phenyl) -ethylamine (241 mg, 1.1 mmol) and triethylamine (151 mg, 1.5 mmol) are dissolved in methanol (5 ml) and the solution stirred at t.amb. for 5 min. Sodium borohydride (37 mg, 1 mmol) is added under a nitrogen atmosphere and the reaction mixture is stirred at RT. for 1 h. Water is added and evaporates the methanol with vacuum. The reaction mixture is extracted twice with diethyl ether, the organic phases are combined, washed once with water and once with an aqueous sat. of NaCl, dried over sodium sulfate, filtered and concentrated in vacuo to give [2- (3-trifluoromethoxy-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) -amine (370 mg, 100%) in form of colorless oil. MS (ISP) = 368.2 (100) (M + H) +. EXAMPLE 2 Obtaining 5-chloro-6-fluoro-1H-indole-7-carboxylic acid [2- (3, 4-dichloro-phenyl) -ethyl] - (4-trimethylsilyl-benzyl) -amide. 5-Chloro-6-fluoro-lH-indole-7-carboxylic acid (2- (3-dichloro-phenyl) -ethyl] - (4-trimethylsilyl-benzyl) -amide in a manner similar to that described in the example from 5-chloro-6-fluoro-lH-indole-7-carboxylic acid and [2- (3,4-dichloro-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) -amine. MS (ISP) = 547.2 / 549.3 / 551.3 (96/100/37) (M + H) +. Obtaining [2- (3, 4-dichloro-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) -amine. 4-Trimethylsilanyl-benzaldehyde (800 mg, 4. 5 mmol) and 2- (3,4-dichloro-phenyl) -ethylamine (1023 mg, 5.4 mmol) in methanol (5 mL) and the solution stirred at rt. for 5 min. Sodium borohydride (166 mg, 4.5 mmol) was added under a nitrogen atmosphere and the reaction mixture was stirred at RT. for 1 h. Water is added and evaporates - - methanol with vacuum. The reaction mixture is extracted twice with diethyl ether, the organic phases are combined, washed once with water and once with an aqueous sat. of NaCl, dried with sodium sulfate, filtered and concentrated in vacuo to obtain [2- (3,4-dichloro-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) -amine (1640 mg, 100% ) in the form of a colorless oil. MS (ISP) = 352.2 / 354.2 (100/74) (M + H) +. NMR-H1 (CDC13, 300 MHz) d = 7.48 (d, 2H), 7.25-7.35 (m, 4H), 7.02 (dd, 2H), 3.79 (s, 2H), 2.75-3.00 (m, 4H), 0.26 (s, 9H). EXAMPLE 3 Preparation of [2- (3-trifluoromethyl-phenyl) -ethyl] - (4-trimethylsilyl-benzyl) -amide of 5-chloro-6-fluoro-lH-indole-7-carboxylic acid. 5-chloro-6-fluoro-lH-indole-7-carboxylic acid (3-trifluoromethyl-phenyl) -ethyl] - (4-trimethylsilyl-benzyl) -amide in a similar way to that described in example 1 from 5-chloro-6-fluoro-lH-indole-7-carboxylic acid and [2- (3-trifluoromethyl-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) -amine. MS (ISP) = 547.3 / 549.4 (100/33) (M + H) +. Obtaining [2- (3-trifluoromethyl-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) -amine [2- (3-trifluoromethyl-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) is obtained -amine in a manner similar to that described in example 1 from 4-trimethylsilanyl-benzaldehyde and 2- - - (3-trifluoromethyl-phenyl) -ethylamine. MS (ISP) = 352.3 (M + H) +. NMR-H1 (CDCl3, 300 MHz) d = 7.48 (m, 4H), 7.39 (m, 2H), 7.27 (d, 2H), 3.81 (s, 2H), 2.80-3.00 (m, 4H), 0.26 ( s, 9H). EXAMPLE 4 Preparation of [2- (4-chloro-phenyl) -ethyl] - (4-trimethylsilyl-benzyl) -amide of 5-chloro-6-fluoro-lH-indole-7-carboxylic acid [2] 5-Chloro-6-fluoro-lH-indole-7-carboxylic acid (chloro-phenyl) -ethyl] - (-trimethylsilyl-benzyl) -amide in a manner similar to that described in Example 1 from acid 5 -chloro-6-fluoro-lH-indole-7-carboxylic acid and [2- (4-chloro-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) -amine. MS (ISP) = 513.3 / 515.3 (100/69) (M + H) +. Obtaining [2- (4-chloro-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) -amine [2- (4-Chloro-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) is obtained -amine in a manner similar to that described in example 1 from 4-trimethylsilanyl-benzaldehyde and 2- (4-chloro-phenyl) -ethylamine. MS (ISP) = 318.1 / 320.3 (100/39) (M + H) +. NMR-H1 (CDC13, 300 MHz) d = 7.47 (d, 2H), 7.23-7.28 (m, 4H), 7.12 (d, 2H), 3.79 (s, 2H), 2.75-3.00 (m, 4H), 0.26 (s, 9H). EXAMPLE 5 Obtaining [2- (4-Fluoro-phenyl) -ethyl] - (4-trimethylsilyl-benzyl) -amide from 5-chloro-6-fluoro-lH- - - indole-7-carboxylic acid [2- (4-Fluoro-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) -amide of 5-chloro-6-fluoro-lH-indole-7-carboxylic acid is obtained similarly to that described in example 1 from 5-chloro-6-fluoro-lH-indole-7-carboxylic acid and [2- (4-fluoro-phenyl) -ethyl] - (4-trimethylsilanyl) benzyl) -amine. MS (ISP) = 497.4 / 499.3 (100/48) (M + H) +. Obtaining [2- (4-fluoro-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) -amine. [2- (4-Fluoro-phenyl) -ethyl] - (4-trimethylsilanyl-benzyl) - amine in a manner similar to that described in Example 1 from 4-trimethylsilanyl-benzaldehyde and 2- (4-fluorophenyl) -ethylamine. MS (ISP) = 302.2 (100) (M + H) +. NMR-H1 (CDCl3, 300 MHz) d = 7.47 (d, 2H), 7.27 (d, 2H), 7.15 (dd, 2H), 6.97 (dt, 2H) 3.79 (s, 2H), 2.75-3.00 (m , 4H), 0.26 (s, 9H). EXAMPLE 6 Obtaining the 5-chloro-6-fluoro-lH-indole-7-carboxylic acid [- (isopropyl-dimethyl-silanyl) -benzyl] - [2- (3-trifluoromethyl-phenyl) -ethyl] -amide The [4- (isopropyl-dimethyl-silanyl) -benzyl] - [2- (3-trifluoromethyl-phenyl) -ethyl] -amide of 5-chloro-6-fluoro-lH-indole-7-carboxylic acid of similar mode to that described in example 1 from 5-chloro-6-fluoro-lH-indole-7-carboxylic acid and [4- (isopropyl-dimethyl-silanyl) -benzyl] - [2- - - (3-trifluoromethyl-phenyl) -ethyl] -amine. MS (ISP) = 575.3 / 576.4 / 577.3 (100/46/40) (M + H) +. Obtaining 4- (isopropyl-dimethyl-silanyl) -benzaldehyde Dissolves 1, -dibromo-benzene (1.18 g, 5 mmol) in THF (15 mL) and cooled to -78 ° C. Under argon atmosphere, a 1.6 M solution of n-butyllithium in hexane (3.13 ml, 5 mmol) is added slowly and with stirring keeping the temperature below -70 ° C. After the addition is complete, the reaction mixture is stirred at -78 ° C for 30 min and the dimethyl-isopropyl-silyl chloride (683 mg, 5 mmol) is carefully added keeping the temperature again below -70 ° C. The reaction mixture was stirred at -78 ° C for 30 min and at this temperature a 1.6 M solution of n-butyllithium in hexane (3.13 ml, 5 mmol) was added keeping the temperature below -70 ° C. After stirring at -78 ° C for 30 min, the DMF (1.1 g, 15 mmol) is added in one portion and the reaction mixture is allowed to warm to RT. Water is added and the solvent is evaporated. The reaction mixture was extracted twice with diethyl ether. The organic phases are combined, dried over sodium sulfate, filtered and the solvent is evaporated, yielding 4- (isopropyl-dimethylsilanyl) -benzaldehyde (900 mg, 87%) as a colorless oil. The product has a sufficient purity to be used directly in the next step. MS (ISP) = 207.1 (M + H) +. NMR-H1 (CDC13, 300 MHz) d = 10.0 (s, 1H), 7.84 (d, J = - - 8. 1 Hz, 2H), 7.67 (d, J = 8.1 Hz, 2H), 0.93-0.99 (m, 7H), 0.28 (s, 6H). Obtaining [4- (isopropyl-dimethyl-silanyl) -benzyl] - [2- (3-trifluoromethyl-phenyl) -ethyl] -amine The [4- (isopropyl-dimethyl-silanyl) -benzyl] - [ 2- (3-trifluoromethyl-phenyl) -ethyl] -amine in a manner similar to that described in example 1 from 4- (isopropyl-dimethyl-silanyl) -benzaldehyde and 2- (3-trifluoromethyl-phenyl) - ethylamine. MS (ISP) = 380.2 (100) (M + H) +. NMR-H1 (CDC13, 300 MHz) d = 7.52-7.42 (m, 6H), 7.26 (d, J = 7.8 Hz, 2H), 3.81 (s, 2H), 2.88-2.96 (m, 4H), 0.95 ( m, 7H), 0.23 (s, 6H). The compounds of the formula I are inhibitors of the cholesteryl ester transfer protein (CETP). Atherosclerosis and associated coronary heart disease is the main cause of mortality in the industrialized world. It has been observed that the risk of developing coronary heart disease is intimately related to certain levels of plasma lipids. The lipids are transported in the blood by lipoproteins. The general structure of lipoproteins consists of a core of neutral lipids (triglycerides and cholesterol esters) and a lining of polar lipids (phospholipids and unesterified cholesterol). There are three different classes of plasma lipoproteins with different core lipid content: low density lipoprotein (LDL), rich in cholesteryl ester (CE); the - - high density lipoprotein (HDL), which is also rich in cholesteryl ester (CE); and very low density lipoprotein (VLDL) that is rich in triglycerides (TG). The different lipoproteins can be separated based on their different flotation density or size. High levels of LDL cholesterol (LDL-C) and triglycerides have a positive correlation, while high levels of HDL cholesterol (HDL-C) have a negative correlation with the risk of developing cardiovascular diseases. The metabolism of plasma lipoprotein can be described as a flow of cholesterol between the liver and other tissues. The mechanism of LDL corresponds to the secretion of VLDL in the liver to supply cholesterol through LDL to tissues. Any alteration in the catabolism of LDL can lead to the absorption of excess cholesterol in the wall of the vessels forming cellular foam and atherosclerosis. The opposite mechanism consists in the mobilization of free cholesterol from peripheral tissues by means of HDL to supply cholesterol to the liver, which eventually excretes it in the form of bile. In humans, a significant portion of cholesteryl esters (CE) is transferred from HDL to the VLDL, LDL mechanism. In this transfer, a plasma glycoprotein of 70,000 daltons is involved, the ester transfer protein of - - cholesteryl (CETP). Mutations of CETP genes associated with CETP deficiency are characterized by high levels of HDL cholesterol (> 60 mg / dl) and reduced cardiovascular risk. These findings are consistent with studies of the pharmacologically mediated inhibition of CETP in the rabbit, which is a strong argument in favor of the inhibition of CETP as a therapeutically valid strategy [Le Goff et al., Pharmacology & Therapeutics 101, 17-38, 2004; Okamoto et al., Nature 406, 203-207, 2000]. There are no fully satisfactory therapies to elevate HDL. Niacin can increase HDL significantly, but it has serious tolerance problems, which reduces its application. Fibrates and HMG CoA reductase inhibitors only increase HDL cholesterol modestly (10-12%). It follows that there is a significant unmet medical demand for an agent that is well tolerated and that can significantly raise plasma HDL levels. The net result of CETP activity is a decrease in HDL-C and an increase in LDL-C. It is believed that this effect on the lipoprotein profile is pro-atherogenic, especially in subjects whose lipid profile carries a higher risk of coronary heart disease. Therefore, inhibiting the activity of CETP creates a potential to reverse this relationship towards a risk - - lower and in the end to protect against coronary heart disease and associated mortality. Accordingly, inhibitors of CETP are useful as medicaments for the treatment and / or prophylaxis of atherosclerosis, peripheral vascular diseases, dyslipidemia, hyperbetalipoproteinemia, hypoalphalipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hereditary hypercholesterolemia, cardiovascular disorders, angina pectoris, ischemia, ischemia. cardiac, apoplexy, myocardial infarction, reperfusion injury, angioplastic restenosis, hypertension and vascular complications of diabetes, obesity or endotoxemia. In addition, the CETP inhibitors can be used in combination with another compound, the compound can be an HMG-CoA reductase inhibitor, a microsomal inhibitor of the triglyceride transfer protein (MTP) / secretion of ApoB, a PPAR activator, a bile acid reabsorption inhibitor, a cholesterol absorption inhibitor, an inhibitor of cholesterol synthesis, a fibrate, niacin, an ion exchange resin, an antioxidant, an ACAT inhibitor or a bile acid sequestrant. As described above, the compounds of the formula I of the present invention can be used as medicaments for the treatment and / or prophylaxis of diseases mediated by CETP inhibitors. Examples of such diseases are atherosclerosis, peripheral vascular diseases, dyslipidemia, hyperbetalipoproteinemia, hypoalphalipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hereditary hypercholesterolemia, cardiovascular disorders, angina pectoris, ischemia, cardiac ischemia, stroke, myocardial infarction, reperfusion injury, angioplastic restenosis. , hypertension and vascular complications of diabetes, obesity or endotoxemia. The use as a medicament for the treatment and / or prevention of dyslipidemia is preferred. Therefore, the invention also relates to pharmaceutical compositions containing a compound defined above and a pharmaceutically acceptable carrier and / or adjuvant. The invention also relates to compounds defined above for the use of therapeutically active substances, in particular therapeutically active substances for the treatment and / or prophylaxis of diseases mediated by CETP inhibitors. Examples of such diseases are atherosclerosis, peripheral vascular diseases, dyslipidemia, hyperbetalipoproteinemia, hypoalphalipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hereditary hypercholesterolemia, cardiovascular disorders, angina pectoris, ischemia, cardiac ischemia, stroke, myocardial infarction, reperfusion injury, angioplastic restenosis, hypertension and vascular complications of diabetes, obesity or endotoxemia. In another embodiment, the invention relates to a method for the treatment and / or prophylaxis of diseases mediated by CETP inhibitors. Examples of such diseases are atherosclerosis, peripheral vascular diseases, dyslipidemia, hyperbetalipoproteinemia, hypoalphalipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hereditary hypercholesterolemia, cardiovascular disorders, angina pectoris, ischemia, cardiac ischemia, stroke, myocardial infarction, reperfusion injury, angioplastic restenosis, hypertension and vascular complications of diabetes, obesity or endotoxemia. A method for the treatment and / or prophylaxis of dyslipidemia is preferred. The invention also relates to the use of the compounds of formula I defined above for the treatment and / or prophylaxis of diseases mediated by CETP inhibitors. Examples of such diseases are atherosclerosis, peripheral vascular diseases, dyslipidemia, hyperbetalipoproteinemia, hypoalphalipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hereditary hypercholesterolemia, cardiovascular disorders, angina pectoris, - - ischemia, cardiac ischemia, stroke, myocardial infarction, reperfusion injury, angioplastic restenosis, hypertension and vascular complications of diabetes, obesity or endotoxemia. The use of the compounds of formula I defined above for the treatment and / or prophylaxis of dyslipidemia is preferred. The invention also relates to the use of the compounds of formula I defined above for the manufacture of medicaments for the treatment and / or prophylaxis of diseases mediated by CETP inhibitors. Examples of such diseases are atherosclerosis, peripheral vascular diseases, dyslipidemia, hyperbetalipoproteinemia, hypoalphalipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hereditary hypercholesterolemia, cardiovascular disorders, angina pectoris, ischemia, cardiac ischemia, stroke, myocardial infarction, reperfusion injury, angioplastic restenosis, hypertension and vascular complications of diabetes, obesity or endotoxemia. The use of the compounds of formula I defined above for the manufacture of medicaments for the treatment and / or prophylaxis of dyslipidemia is preferred. The CETP inhibitors are also useful in combination with another compound, the compound is an HMG-CoA reductase inhibitor, a microsomal protein inhibitor. - - triglyceride transfer (MTP) / secretion of ApoB, a PPAR activator, a bile acid reabsorption inhibitor, a cholesterol absorption inhibitor, an inhibitor of cholesterol synthesis, a fibrate, a niacin, a resin of ion exchange, an antioxidant, an ACAT inhibitor or a bile acid sequestrant. Therefore, the invention also relates to pharmaceutical compositions containing a compound of the formula I already defined above in combination with a reductase inhibitor HMG-CoA, an inhibitor of the microsomal triglyceride transfer protein (MTP) / secretion of ApoB, a PPAR activator, a bile acid reuptake inhibitor, a cholesterol absorption inhibitor, an inhibitor of cholesterol synthesis, a fibrate, a niacin, an ion exchange resin, an antioxidant, an ACAT inhibitor or a bile acid sequestrant, as well as a pharmaceutically acceptable excipient and / or adjuvant.

The invention also relates to the use of the compounds of the formula I already defined above in combination with a reductase inhibitor HMG-CoA, an inhibitor of the microsomal triglyceride transfer protein (MTP) / secretion of ApoB, an activator of PPAR, a bile acid reuptake inhibitor, a cholesterol absorption inhibitor, an inhibitor of cholesterol synthesis, a fibrate, a niacin, an ion exchange resin, a antioxidant, an ACAT inhibitor or a bile acid sequestrant for the treatment and / or prophylaxis of diseases such as atherosclerosis, peripheral vascular diseases, dyslipidemia, hyperbetalipoproteinemia, hypoalphalipoproteinemia, hypercholesterolemia, hypertriglyceridemia, hereditary hypercholesterolemia, cardiovascular disorders, angina pectoris, ischemia, cardiac ischemia, stroke, myocardial infarction, reperfusion injury, angioplastic restenosis, hypertension and vascular complications of diabetes, obesity or endotoxemia, as well as the use of such combination for the manufacture of the corresponding drugs. The compounds of formula I and their pharmaceutically acceptable salts possess valuable pharmacological properties. It has been found in particular that the compounds of the present invention are inhibitors of the cholesteryl ester transfer protein (CETP). The following tests are carried out in order to determine the activity of the compounds of the formula I. The activity of the CETP inhibitors is determined using a buffer assay system. Partially purified CETP transfers radiolabelled cholesteryl esters from the particles of an HDL donor to the LDL acceptor particles labeled with biotin. The reaction is interrupted by the addition of test mats of proximity of scintillation (SPA) on which streptavidin has been fixed. These spheres capture the biotinylated acceptor particles and the transferred radioactivity is measured. The detection system is acquired and applied according to the manufacturer's recommendations (Amersham Biosciences). The inhibitory activity of the compounds is determined as a percentage of the activity of the positive control containing the CETP together with donor and acceptor particles. A series of dilutions of the compounds is carried out in order to determine the IC50 values. The activity of the compounds is then measured in the presence of plasma using the same assay described in previous paragraphs, except that the source of CEPT is a human serum to which lipoproteins have been extracted (LPDS). The inhibitory activity of the compounds is determined as a percentage of the activity of the positive control containing all the test components, except the compound of the invention. A series of dilutions of the compounds is carried out in order to determine the IC50 values. Under the conditions of the last test, the compounds of the present invention have IC 50 values within the range of 1 nM to 100 μ ?, for example between 1 nM and 1 μ? and preferably between 1 nM and 200 nM. The following table shows the measured values of some selected compounds of the present invention.

- - The "in vivo" activity of the compounds of the formula I is determined in hamster according to the following method: Male hamsters of the golden Syrian breed (age: 6 weeks, weight: 100-130 g) receive under standard diet conditions Compounds in the morning by oral administration using an appropriate vehicle; the blood is extracted 2 h later by retro-orbital bleeding with isoflurane anesthesia and the animals are sacrificed 7 h later. The plasma is separated from the blood using low speed centrifugation and the plasma CETP activity is measured using the radioactive activity assay of the CETP described above, except that diluted plasma is now used in place of LPDS. The "in vivo" inhibition of CETP is expressed in the form of remaining CETP activity in the plasma of the treated animals, compared to the CEPT activity in the plasma of the animals treated with a placebo.

The effectiveness of the compounds in modulating plasma lipid levels is determined in hamsters after 7 days of daily administration of the compounds. Male hamsters are acclimated for 3-4 days to receive the - - I think in the form of a paste containing 10 g of feed and 10 g of water per day. The compounds are mixed in this paste and each morning for 7 days they are administered a portion containing the convenient amount of the compounds. Alternatively, the compounds may be delivered by oral administration using the appropriate vehicle. Blood is withdrawn before treatment with the compound by retro-orbital bleeding and animals sacrificed at the end of treatment. The plasma is separated from the blood by low speed centrifugation and selected organs are removed (eg liver, fat, brain, etc.). The effects of the compounds on plasma lipid levels are determined by measuring total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides using enzymatic colorimetric assays (Roche Diagnostic GmbH, Mannheim, Germany). The HDL-C, LDL-C and VLDL-C values are preferably quantified using size exclusion chromatography on a Superpose-6 column by applying the SMART ™ system (Pharmacia). The distribution of lipoprotein is calculated assuming a Gaussian distribution for each peak, using a non-linear curve fitting procedure, of minimum squares, to calculate the area under the curve. Plasma samples are also used to quantify the activity of CETP in the manner described above. The concentration of the compounds in - - plasma and selected tissues, for example liver, fat, heart, muscles and brain. The efficacy of the compounds in modulating lipid levels in plasma in hamsters fed cholesterol / fat is also determined. The test method is identical to that described above, except that the animals receive a feed diet enriched with 10 (w / w) saturated fat and 0.05% (w / w) cholesterol. The animals receive this high-fat diet for 2 weeks before starting the administration of the compounds and continue to receive this diet during the study. The 2-week pretreatment induces an increase in plasma cholesterol and triglyceride levels allowing a better evaluation of the decrease in LDL-C and triglycerides. The efficacy of the compounds in their ability to acutely increase HDL-C is evaluated in cynomolgus monkeys. The animals are fed a standard primate maintenance diet. The compounds are formulated with an appropriate vehicle and administered to the animals orally. The blood is drawn before and at different times after administration of the compounds (usually 30 min, 1 h, 2 h, 4 h, 7 h and 24 h). The plasma is separated from the blood by a low speed centrifugation and the activity of the CETP and the plasma lipids is quantified. The potency and effectiveness of the compounds can be assessed by measuring the - - increase of HDL-C after this single dose administration. In this pharmacodynamic model, extension can be evaluated together with the kinetics of the pharmacological effect. The compounds of the formula I and their pharmaceutically acceptable salts and esters can be used as medicaments, for example in the form of pharmaceutical preparations for enteral, parenteral or topical administration. They can be administered, for example, perorally, eg in the form of tablets, coated tablets, dragees, hard or soft gelatine capsules, solutions, emulsions or suspensions; rectal, eg in the form of suppositories; parenterally, eg in the form of injectable solutions or solutions for infusion; or topical, eg in the form of ointments, creams or oils. The production of the pharmaceutical preparations can be carried out in a manner that will be familiar to any person skilled in the art, incorporating the described compounds of the formula I or their pharmaceutically acceptable salts, into a galenic administration form together with the solid or liquid excipient materials, suitable, non-toxic, inert, therapeutically compatible, and, if desired, together with the usual pharmaceutically acceptable adjuvants. The suitable excipient materials are not only the inorganic excipient materials, but also the organic excipient materials. Therefore, in tablets, coated tablets, dragees and gelatin capsules hard, eg, lactose, corn starch or derivatives thereof, talc, stearic acid or its salts can be used. Suitable excipient materials for soft gelatine capsules are, for example, vegetable oils, waxes, fats and semi-solid and liquid polyols (however, depending on the nature of the active ingredient, it may not be necessary to use excipients in the case of soft gelatine capsules). The suitable excipient materials for the production of solutions and syrups are, eg, water, polyols, sucrose, invert sugar and the like. The suitable excipient materials for injectable solutions are, eg, water, alcohols, polyols, glycerin and vegetable oils. The excipient materials suitable for suppositories are, for example, natural or hydrogenated oils, waxes, fats and semi-liquid or liquid polyols. Suitable excipient materials for topical preparations are glycerides, synthetic and synthetic glycerides, hydrogenated oils, liquid waxes, liquid paraffins, liquid fatty alcohols, sterols, polyethylene glycols and cellulose derivatives.

As stabilizers, preservatives, wetting agents and emulsifiers, agents are considered as pharmaceutical adjuvants. - - improve the consistency, flavor improving agents, salts to vary the osmotic pressure, buffer substances, colorants, dyes, masking agents and antioxidants. The dosage of the compounds of the formula I can vary within wide limits depending on the diseases that are intended to be controlled, the age and the individual state of health of the patient and the mode of administration and should, of course, conform to the requirements individual of each particular case. For adult patients, a daily dose of 1 mg to 1000 mg, especially 1 mg to 100 mg, is taken into consideration. Depending on the daily dose chosen, it may be advisable to administer it divided into several conditions. The pharmaceutical preparations conveniently contain from 0.1 to 500 mg, preferably from 0.5 to 100 mg of a compound of the formula I. The following examples are presented to illustrate the present invention in greater detail. However, it is not intended in any way to limit the scope of the present invention with them.

Example A: film coated tablets The active ingredient is screened and mixed with microcrystalline cellulose and the mixture is granulated with a solution of polyvinylpyrrolidone in water. The granulate is mixed with sodium starch glycolate and magnesium stearate and compressed, obtaining kernels of 120 and 350 mg, respectively. The cores are coated with an aqueous solution / suspension of the film layer composition just described.

- - Example B: capsules The components are sifted, mixed and packed in size 2 capsules. Example C: injectable solutions Example D: soft gelatin capsules - - The active ingredient is dissolved in a melt of the other ingredients and the mixture is filled into soft gelatin capsules of the appropriate size. The soft gelatine capsules and their contents are treated according to the usual procedures. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims (9)

1. - -
2. CLAIMS Having described the invention as above, the content of the following claims is claimed as property: 1. Compound of the formula I
3. (I) characterized in that -XY-is -CRa = CRc- or -CRa = N- or -CRaRb-CRcRd-, in which Ra, Rb, Rc and Rd are independently chosen from the group consisting of hydrogen and Ci ~ c8 alkyl; R1, R2, R4 and R5 are independently selected from the group consisting of hydrogen, Ci-Ce alkyl, Ci-Cs alkoxy, halogen and haloCi-C8 alkyl; R3 is Si (Ci-C6 alkyl) 3; R6 is selected from the group consisting of hydrogen and Ci-Ce alkyl; R7 is selected from the group consisting of hydrogen, Ci-Cg alkyl, hydroxy and halogen; - - is selected from the group consisting of Ci-Cg alkyl, C2-C8 alkenyl, halogen-Ci-C8 alkyl, heterocyclyl, heteroaryl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halogen-Ci-C8 alkyl, halo-Ci-C8 alkoxy and halogen, phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halogen- Ci-C8 alkyl, halo-Ci-C8 alkoxy and halogen, -OR12, wherein R12 is Ci-C8 alkyl or phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, alkoxy Ci-C8, halogeno-Ci-C8 alkyl, halo-Ci-C8 alkoxy and halogen, -NR13R14, wherein R13 and R14 independently are selected from hydrogen, Ci-C8 alkyl, and phenyl, which is unsubstituted or substituted by one or two groups independently chosen from Ci-C8 alkyl, Ci-C8 alkoxy, halo-Ci-C8 alkyl, halo-Ci-C8 alkoxy and halo geno, and -C (0) -OR15, wherein R15 is hydrogen or Ci-C8 alkyl; 0 and R11 independently of each other are selected from the group consisting of hydrogen, Ci-C8 alkyl, cycloalkyl, Ci-C8 alkoxy, haloC1-C8 alkyl and - - halogen; n is the number 1, 2 or 3; and all its pharmaceutically acceptable salts. Compound according to claim 1, characterized in that R3 is Si (CH3) 3 or Si (CH3) 2CH (CH3) 2. 3. Process for obtaining compounds of the formula I according to claim 1, characterized in that the process consists of: a) reacting an acid of formula II
4. (II) wherein -X-Y-, R9, R10 and R11 have the meanings defined in claim 1 and R is hydrogen or Ci-Ce alkyl, with an amine of formula III
5. (III) wherein R1 to R8 and n have the meanings defined in claim 1, in the presence of a binding agent; or, alternatively, - - b) reacting a halogenated derivative formula IV
6. (IV) in which -XY-, R9, R10 and R11 have the meanings defined in formula 1 and Hal means halogen, with an amine of formula III, in the presence of a suitable catalyst and carbon monoxide and, if desired, to convert the obtained compound to a pharmaceutically acceptable acid addition salt. 4. Pharmaceutical compositions characterized in that they contain a compound according to claim 1 or 2, as well as a pharmaceutically acceptable carrier and / or adjuvant. 5. Pharmaceutical compositions according to claim 4, characterized in that they are for the treatment and / or prophylaxis of diseases mediated by CETP. 6. Compounds according to claim 1 or 2, characterized in that they are for use as therapeutically active substances.
7. 7. Compounds according to claim 1 or - - 2, characterized in that they are for use as therapeutically active substances intended for the treatment and / or prophylaxis of diseases mediated by CETP.
8. 8. Method for the treatment and / or prophylaxis of diseases mediated by CETP, characterized in that it consists of administering a compound according to claim 1 or 2 to a human being or an animal.
9. 9. Use of the compounds according to claim 1 or 2, for the manufacture of a medicament for the treatment and / or prophylaxis of diseases mediated by CETP.