MXPA06009533A - Compounds for the treatment of diseases - Google Patents

Abstract

The invention relates to compounds of formula (1) and to processes for the preparation of, intermediates used in the preparation of, compositions containing and the uses of, such derivatives. The compounds according to the present invention are useful in numerous diseases, disorders and conditions, in particular inflammatory, allergic and respiratory diseases, disorders and conditions.

Description

COMPOUNDS FOR THE TREATMENT OF DISEASES Field of the Invention This invention relates to β2-agonists of the general formula: wherein R1, R2, n and Q1 have the meanings indicated below and to processes for their preparation, to compositions containing them and to the uses of such derivatives. Background of the Invention Adrenoceptors are members of the large superfamily of G-protein coupled receptors. The adrenoceptor subfamily is in turn divided into the subfamilies a and β, the β subfamily being composed of at least 3 receptor subtypes: β1, ß2 and ß3. These receptors show differential expression patterns in tissues of different systems and organs of mammals. Β2 adrenergic receptors (β2) are expressed mainly in smooth muscle cells (eg vascular, bronchial, uterine or intestinal smooth muscle), whereas β3 adrenergic receptors are expressed mainly in fatty tissues (therefore, β3 agonists) may be potentially useful in the treatment of obesity and diabetes) and ß1 adrenergic receptors are mainly expressed in cardiac tissues (therefore, β1 agonists are used primarily as cardiac stimulants).

In the literature, pathophysiology and treatments of respiratory diseases have been extensively reviewed (for reference, see Barnes, PJ Chest, 1997, 111: 2, p 17S-26S and Bryan, SA et al, Expert Opinion on Investigational drugs, 2000, 9: 1, pp. 25-42) and, therefore, only a brief summary will be included in this document to provide background information. Glucocorticosteroids, anti-leukotrienes, theophylline, chromones, anti-cholinergics and β2-agonists are classes of drugs that are currently used to treat allergic and non-allergic respiratory diseases such as asthma and chronic obstructive airway disease ( COPD). Treatment guidelines for these diseases include short-acting and long-term inhaled β2-agonists. For "recovery" bronchodilation, β2-agonists with rapid onset of action and short-acting are used, while long-acting forms provide sustained relief and are used as maintenance therapy. Bronchodilation is mediated by the agonism of the β2-adrenoceptor expressed in the smooth muscle cells of the respiratory tract, which produces a relaxation and, therefore, bronchodilation. Thus, as functional antagonists, β2-agonists can prevent and reverse the effects of all bronchoconstrictor substances, including leukotriene D4 (LTD4), acetylcholine, bradykinin, prostaglandins, histamine and endothelin. As the ß2 receptors are so widely distributed in The airways, the ß2 agonists can also affect other cell types that play a role in asthma. For example, it has been reported that ß2 agonists can stabilize mast cells. Inhibition of the release of bronchoconstrictor substances may be the way in which ß2 agonists block allergen-induced bronchoconstriction, exercise, and cold air. In addition, β2-agonists inhibit cholinergic neurotransmission in the human respiratory tract, which can reduce cholinergic-reflex bronchoconstriction. It has also been established that β2-adrenoceptors, in addition to the respiratory tract, are also expressed in other organs and tissues and, thus, β2-agonists, such as those described in the present invention, can have application in the treatment of other diseases such as, but not limited to, those of the nervous system, premature birth, congestive heart failure, depression, inflammatory and allergic skin diseases, psoriasis, skin proliferative diseases, glaucoma and in conditions in which it is positive to reduce the gastric acidity, particularly in gastric and peptic ulcers. However, many β2 agonists are limited in their use due to their low selectivity or to their adverse side effects produced by a high systemic exposure and mediated mainly by the action on ß2 adrenoceptors expressed outside the respiratory tract (muscle tremor, tachycardia, palpitations, agitation). Therefore, there is the need for better agents of this class. Accordingly, there is still a need for new β2 agonists having an appropriate pharmacological profile, for example, in terms of potency, selectivity, pharmacokinetics or duration of action. In this context, the present invention relates to novel β2 agonists. Detailed Description of the Invention The invention relates to the compounds of general formula (1): wherein the group (CH2) pC (= O) Q1 is in the meta or para position, -R1 and R2 are independently selected from H and C1-C4 alkyl, -n is 0, 1 or 2 and -Q1 is a group selected between, -NR8-Q2-A or * -NR8-Q3, where p is 1 or 2 and g is 1 or 2, Q2 is a single bond or a C1-C4 alkylene optionally substituted with OH, -R8 is H or C1-C4 alkyl and, 3 9 10 9 - Q is C1-C6 alkyl optionally substituted with NR R, OR or phenoxy, - A is selected from: C3-C10 cycloalkyl, said cycloalkyl being optionally linked with one or more, preferably 1, 2, 3 or 4, carbon atoms , and optionally being substituted with a hydroxy group, a 5-6 membered heterocyclic group, optionally aromatic, containing one or two heteroatoms selected from O, N or S, optionally substituted with one or two substituents selected from C 1 -C 4 alkyl , benzyl and cyclopropylmethyl or a group quinolyl or isoquinolyl. - R3, R4, R5, R6 and R7 are the same or different and are selected between H, C1-C4 alkyl, OR9, SR9, SOR9, SO2R9, halo, CN, CF3, OCF3) SO NR9R10, COOR9, CONR9R10, NR9R10, NHCOR10 and phenyl optionally substituted with OH, 9 -R and R are the same or and are selected from H or C 1 -C 4 alkyl, -R 11 is selected from H or OH, and, 12 13 -R and R are the same or different and are selected from H, C 1 -C 4 alkyl optionally substituted with OR 9, OR 9, C (= O) NH2, C (= O) CH3, N (CH3) C (= O) CH3, C (= O) OR9, phenyl optionally substituted with halogen, pyridyl optionally substituted with CN, oxadiazolyl optionally substituted with C1 alkyl -C4, and, - * represents the point of attachment to the carbonyl group; or, if appropriate, their pharmaceutically acceptable salts and / or isomers, tautomers, solvates or isotopic variations thereof. The compounds of formula (1) are agonists of the β2 receptors which are particularly useful for the treatment of diseases and / or conditions mediated by β2, showing an excellent potency, in particular when administered by inhalation. In general formula (1) above, C 1 -C 4 alkyl and C 1 -C 4 alkylene refer to a straight or branched chain group containing 1, 2, 3 or 4 carbon atoms. C 1 -C 6 alkyl refers to a straight or branched chain group containing 1, 2, 3, 4, 5 or 6 carbon atoms. This also applies if they have substituents or appear as substituents of other radicals, for example on O-alkyl radicals (C 1 -C 4), S-alkyl radicals (C 1 -C 4) etc. Examples of suitable (C1-C4) alkyl radicals are methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, sec-butyl, tere-butyl ... Examples of O-alkyl radicals (C1 -C4) suitable methoxy, ethoxy, n-propyloxy, iso-propyloxy, n-butyloxy, iso-butyloxy, sec-butyloxy and tert-butyloxy .... C3-C10 cycloalkyl in which 2 or more carbon atoms are optionally attached with one or more carbon atoms include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, bicyclo [3.1.1] heptane, bicyclo [2.2.1] heptane, bicyclo [2.2.2] octane. Preferred cyclohexyl and adamantyl groups are cycloalkyl groups. Non-limiting examples of "5- to 6-membered heterocyclic group, optionally aromatic, containing one or two heteroatoms selected from O, N or S" morpholinyl, pyrrolidinyl, piperidyl, piperazinyl, pyrazolyl, thienyl, furanyl, imidazolyl, isothiazolyl, thiazolyl , isoxazolyl, oxazolyl, pyridyl and pyrimidyl. Preferably, said heterocyclic group contains a nitrogen atom, two nitrogen atoms or a nitrogen atom and an oxygen atom. Preferred 5-6 membered aromatic heterocyclic groups are pyrazolyl and pyridyl.

Preferred 5- to 6-membered non-aromatic heterocyclic groups are morpholinyl, pyrrolidinyl, piperidyl and piperazinyl. Finally, it refers to a halogen atom selected from the group consisting of fluorine, chlorine, bromine and iodine, in particular fluorine or chlorine. Hereinafter, the free bond in the phenyl group as indicated in the structure shown below, means that the phenyl may be substituted in the meta or para position. The compounds of formula (1) they can be prepared using conventional methods such as the following illustrative methods in which Q1, Q2, R1, R2, A and n are as previously defined for the compounds of formula (1) unless otherwise indicated. The amide derivatives of formula (1) can be prepared by coupling an acid of formula (2): with an amine of formula NHR8-Q2-A, NHR8-Q3 -OO The coupling is generally carried out in an excess of said amine as an acid receptor with a conventional binding agent (for example 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride or N, N'-dicyclohexylcarbodiimide), optionally in the presence of a catalyst (for example 1-hydroxybenzotriazole hydrate or 1-hydroxy-7-azabenzotriazole) and optionally in the presence of a tertiary amine base (for example N-methylmorpholine, triethylamine or diisopropylethylamine). The reaction can be carried out in a suitable solvent such as pyridine, dimethylformamide, tetrahydro- furan, dimethisulfoxide, dichloromethane? /, / V-dimethylacetamide, or ethyl acetate and at a temperature between 10 ° C and 40 ° C (room temperature) for a period of 1-24 hours. Said amines are commercially available or can be prepared by conventional methods well known to those skilled in the art (for example reduction, oxidation, alkylation, transition metal mediated coupling, protection, deprotection etc.) from material available in the art. market. The acid of formula (2) can be prepared from the corresponding ester of formula (4): where Ra is a suitable acid protecting group, preferably a (C 1 -C 4) alkyl group, including, but not limited to, methyl and ethyl, according to any method well known to those skilled in the art to prepare an acid from of an ester without modifying the rest of the molecule. For example, the ester can be hydrolyzed by treatment with an aqueous acid or base (for example hydrogen chloride, potassium hydroxide, sodium hydroxide or lithium hydroxide), optionally in the presence of a solvent or mixture of solvents (for example water, 1, 4-dioxane, tetrahydro- furan / water), at a temperature between 20 ° C and 100 ° C, for a period of 1 to 40 hours. The ester of formula (4) can be prepared by removal of the phenolic protecting group of the compound of formula (5), where PG is defined as a suitable phenolic protecting group, typically an alkyl or alkoxy ether (for example methyl, benzyl, methoxymethyl) and preferably it is benzyl.

Suitable reagents to achieve this deprotection are described in T.W. GREENE, Protective Groups in Organic Synthesis, A. Wiley-lnterscience 10 Publication, 1981. In a typical procedure, when PG represents benzyl, this can be achieved by hydrogenation using a suitable catalyst (e.g., palladium hydroxide or palladium on carbon) in a suitable solvent such as ethanol or methanol in a hydrogen atmosphere, optionally at an elevated pressure (for example 413.57 kPa (60 psi)) and at a temperature between room temperature and 60 ° C for 8-24 hours. Alternatively, transfer hydrogenation with a suitable catalyst (e.g., palladium hydroxide) and ammonium formate can be used as a source of hydrogen in a suitable solvent such as ethanol and at a temperature between room temperature and 60 ° C. The ester of formula (5) can be prepared by reaction of an amine of formula (6): where Ra and n are as previously defined, with a bromide of formula (7): In a typical procedure, the amine of formula (6) is reacted with a bromide of formula (7) optionally in the presence of a solvent or mixture of solvents (for example dimethyl sulfoxide, toluene,? /,? / - dimethylformamide, acetonitrile, THF), optionally in the presence of a suitable base (for example triethylamine, diisopropylethylamine, potassium carbonate) at a temperature between 60 ° C and 120 ° C, for 12 to 120 hours. Subsequently, the resulting amino ketone intermediate can be reduced using a suitable reducing agent such as sodium borohydride or diisobutyl aluminum hydride. The bromide of formula (7) can be prepared from the ketone of the formula (19): by bromination with a suitable bromine source. In a typical procedure, the ketone is treated with a brominating agent (for example E NBr3) in a suitable solvent such as THF and methanol at room temperature for about 24 hours. The ketone of formula (19) is available in the market. The amine of formula (6), wherein R 1 is Me and R 2 is H, can be prepared as the (R) or (S) -enantiomer from the corresponding protected amine of formula (8): where Ra and n are as previously defined and Rb and Rc represent any suitable substituent such that HNRbRc is a chiral amine (for example, Rb can be hydrogen and Rc can be a-methylbenzyl), with the proviso that the bonds between N and Rb and N and Rc can be easily cleaved to give the free amine of formula (5) using conventional methodology for the cleavage of nitrogen protecting groups. no, such as the one that can be found in T.W. GREENE, Protective Groups in Organic Synthesis, A. Wiley-lnterscience Publication, 1981. The amine of formula (8) can be prepared as a single diastereomer by reaction of an amine of formula HNRbRc with a ketone of formula (9): where Re, Rb, Rc and n are as previously defined. In a typical procedure, the reaction of the formula ketone (9) with the amine of the formula HNRbRc leads to a chiral intermediate which in turn is reduced with a suitable reducing agent (for example sodium cyanoborohydride of the formula NaCNBH3 or sodium triacetoxyborohydride of the formula Na (OAc) 3BH) optionally in the presence of an agent drying (for example molecular sieves or magnesium sulfate) and optionally in the presence of an acid catalyst (for example acetic acid) to give the amine of formula (8) in the form of a mixture of diastereomers. The reaction is generally carried out in a solvent such as tetrahydrofuran or dichloromethane at a temperature between 20 ° C and 80 ° C for 3 to 72 hours. Subsequently, the resulting product is transformed into the hydrochloride salt and selectively crystallized in a suitable solvent or in a mixture of solvents (for example isopropanol, ethanol, methanol, diisopropyl ether or diisopropyl ether / methane!) to give (8) as a single diastereomer. The ketone of formula (9) in which n = 1 can be prepared by a palladium-mediated coupling of an aryl halide of formula (10): where Ra is as previously defined and Hal represents a halogen atom, which includes but is not limited to bromine and iodine, with an enolate or enolate equivalent. In a typical procedure, the aryl halide of formula (10) is reacted with a tin enolate generated in situ by treatment of isopropenyl acetate with tri-n-butyltin methoxide of the formula BusSnOMe in the presence of a suitable palladium catalyst (palladium / tri-ortho-tolylphosphine acetate of formula Pd (OAc) 2 / P (o-Tol) 3) in a non-polar solvent (for example toluene, benzene, hexane). Preferably, the reaction is carried out at a temperature between 80 ° C and 110 ° C for 6 to 16 hours. The aryl halide of formula (10) can be obtained by esterification of the corresponding acid of formula (11): wherein Hal is as previously defined, according to any method well known to those skilled in the art to prepare an ester from an acid without modifying the remainder of the molecule. In a typical procedure, the acid of formula (11) is reacted with an alcohol solvent of the formula RaOH, where Ra is as previously defined, in the presence of an acid such as hydrogen chloride at a temperature between 10 ° C and 40 ° C (room temperature) and for 8 to 16 hours. The acid of formula (11) is a commercial product. The amine of formula (6), wherein R1 and R2 are C1-C4 alkyl, can be prepared according to the following scheme. Fsqnema 1 (6) where R1, R2 and Ra are as previously defined. In a typical procedure, the ester of formula (12) is reacted with an "activated" alkyl (organometallic alkyl such as R2 mgBr, R2 mgCl or R2Li) to give the corresponding tertiary alcohol of formula (13) using the method described above. Subsequently, said tertiary alcohol of formula (13) is treated with an alkyl nitrile (for example acetonitrile, chloroacetonitrile) in the presence of an acid (for example sulfuric acid, acetic acid) to give a protected intermediate which is cleaved in turn using methodology conventional for cleaving nitrogen protecting groups such as mentioned in textbooks. The resulting amino acid is esterified using the method described herein to give the amine of formula (6). Alternatively, the amine of formula (6), wherein R1 and R2 are C1-C4 alkyl and n = 0, can be prepared according to the following scheme: Ffiqnema 9 where R1, R2 and Ra are as previously defined. In a typical procedure, the ester of formula (14) is reacted with an "activated" alkyl group (organometallic alkyl such as R2 mgBr, R2 mgCI or R2Li) to give the corresponding tertiary alcohol of formula (15) using the method described above. Subsequently, said tertiary alcohol of formula (15) is treated with an alkyl nitrile (for example acetonitrile, chloroacetonitrile) in the presence of an acid (for example sulfuric acid, acetic acid) to give a protected intermediate which in turn is cleaved using methodology conventional for cleaving nitrogen protecting groups such as mentioned in textbooks, to give bromine amine (16). The resultant bromine amine (16) is treated with a suitable palladium catalyst (e.g. [1, 1 * -bis (diphenylphosphine) ferrocene] dichloropalladium (ll)) in an atmosphere of carbon monoxide using RaOH as solvent ( MeOH, EtOH) at a temperature (100 ° C) and pressure (689.29 kPa (100 psi)) raised to give the ester of formula (6). The ketone of formula (9) in which n = 2 can be prepared by reduction of an alkene of formula (17): In a typical procedure, a solution of the olefin of formula (17) in a suitable solvent (for example methanol, ethanol, ethyl acetate) is treated with a palladium catalyst (for example 10% palladium on carbon) and stirred under an atmosphere of hydrogen, optionally at elevated pressure ( for example 413.57 kPa (60 psi)), at a temperature between ambient temperature and 60 ° C and for 8 to 24 hours. The alkene of formula (17) can be prepared by a palladium-mediated coupling of an activated olefin with an aryl halide of formula (18): In a typical procedure, the aryl halide (18) is coupled with a vinyl ester (for example, methyl acrylate) in the presence of a suitable palladium catalyst (for example tetrakis (triphenylphosphine) palladium (0) of formula Pd ( PPh3) 4, palladium acetate / tri-ortho-tolylphosphine of formula Pd (OAc) 2 / P (o-tol) 3 or (diphenylphosphine) ferrocenyl palladium chloride of formula dppfPdC) in a suitable solvent (for example acetonitrile, N , N-dimethylformamide, toluene), optionally in the presence of a base such as triethylamine at a temperature between 40 ° C and 110 ° C and for 8 to 24 hours. The ketone of formula (18) is a commercial product. Alternatively, a compound of formula (1) can be prepared by reaction of a bromide of formula (7) and an amine of formula (20): where R1, R2, Q1 and n are as previously defined for the compounds of formula (1) unless otherwise indicated. In a typical procedure, the amine of formula (20) is reacted with a bromide of formula (7) optionally in the presence of a solvent or mixture of solvents (for example dimethyl sulfoxide, toluene, N,? / - dimethylformamide, acetonitrile), optionally in the presence of a suitable base (for example triethylamine, diisopropylethylamine, potassium carbonate) at a temperature between 60 ° C and 120 ° C, for 12 to 48 hours. The resulting aminoacetone intermediate can be reduced using a suitable reducing agent such as sodium borohydride or diisobutyl aluminum hydride. The amide of formula (20) can be prepared by coupling an acid of formula (21) incorporating a suitable amine protecting group with an amine of formula -R12 HN. N- R12 " HO O Generally, the coupling is carried out in an excess of said amine as acid receptor, with a conventional coupling agent (for example 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride or N, N'-dicyclohexylcarbodiimide), optionally in the presence of a catalyst (for example 1-hydroxybenzotriazole hydrate or 1-hydroxy-7-azabenzotriazole) and optionally in the presence of a tertiary amine base (for example N-methylmorpholine, triethylamine or diisopropylethylamine). The reaction can be carried out in a suitable solvent such as pyridine, dimethylformamide, tetrahydrofuran, dimethisulfoxide, dichloromethane or ethyl acetate and at a temperature between 10 ° C and 40 ° C (room temperature) for a period of 1 to 24 hours. Said amine is commercially available or can be prepared by conventional methods well known to those skilled in the art (eg reduction, oxidation, alkylation, transition metal mediated coupling, protection, deprotection etc.) from materials available in the art. market. The acid of formula (21) can be prepared from the corresponding ester of formula (6). The acid of formula (21), wherein R1 and R2 are C1-C4 alkyl, can be prepared from the ester (6) by incorporating a suitable amine protecting group P1 before or after acid formation. where Ra is a suitable acid protecting group, preferably a (C 1 -C 4) alkyl group, including, but not limited to, methyl and ethyl, according to any method well known to those skilled in the art for preparing an acid from an ester without modifying the rest of the molecule. For example, the ester can be hydrolysed by treatment with an aqueous acid or base (for example, hydrogen chloride, potassium hydroxide, sodium hydroxide or lithium hydroxide), optionally in the presence of a solvent or mixture of solvents (for example water, 1, 4-dioxane, tetrahydrofuran / water), at a temperature comprised between 20 ° C and 100 ° C and for a period of 1 to 40 hours. The amine of formula (6), wherein R1 and R2 are H, can be prepared according to the following scheme: Scheme 3 (22) (23) where R1, R2 and Ra are as previously defined. In a typical procedure, the acid of formula (22) is preferably reduced to the corresponding alcohol (23) in the presence of the ester. This can be done by the formation of the acyl imidazole or mixed anhydride and subsequent reduction with sodium borohydride or other suitable reducing agent. Subsequently, said primary alcohol of formula (23) is transformed into a leaving group such as mesylate, tosylate, bromide or iodide and is displaced with an appropriate amine nucleophile. The preferred nucleophile is azide which can then be reduced to the primary amine by hydrogenation or with triphenylphosphine. Alternative nucleophiles could include ammonia or alkylamines such as benzylatin or allylamine and the subsequent cleavage of the alkyl group to produce the amine. For some of the steps of the preparation processes described above of the compounds of formula (1), it may be necessary to protect potentially reactive functions that are not desired to react and consequently cleave such protective groups. In such a case, any compatible protective radical can be used. In particular, protection and deprotection methods such as those described by T.W. GREENE (Protective Groups in Organic Synthesis, A. Wiley-! Nterscience Publication, 1981) or P. J. Kocienski (Protecting groups, Georg Thieme Verlag, 1994). For example, in the previous processes, the bromine of (7) can be substituted with a protected bromine compound of formula The bromide can be prepared racemicly using a reducing agent such as sodium borohydride in a suitable solvent such as ethanol. Alternatively, the alcohol can be prepared as an enantiomer (R) or (S) according to methods that are well described in the literature (Tetrahedron Letters 1994, 35 (50), 10 9375). The compound of formula (I) would be obtained by deprotection of a compound of formula wherein PG represents a suitable alcohol protecting group, typically a silyl group such as TBDMS or TMS, and preferably TBDMS. Deprotection can be done according to the methods described in conventional textbooks such as "Protective Groups in Organic Synthesis "by TW Greene, A. Wiley-lnterscience Publication, 1981. In a typical procedure, in which PG represents TBDMS, the compound of formula (24) is treated with 10-18 equiv. Of ammonium fluoride in aqueous methanol. about 45 ° C for a period between 18 and 42 hours An alternative agent for the deprotection would be an equivalent of triethylamine trihydrofluoride in tetrahydrofuran or a suitable solvent at room temperature for 12 hours All the above reactions and preparations of new materials of The starting materials used in the preceding processes are conventional and those skilled in the art will know the reaction conditions for their preparation or preparation as well as methods for isolating the desired products, with reference to bibliographic precedents and the examples and preparations thereof. compounds of formula (1) as well as the intermediates for the preparation of the They can be purified according to various well-known procedures, such as for example crystallization or chromatography. In a preferred embodiment of the invention, Q2 is a single bond. In a preferred embodiment of the invention, A is selected from morpholinyl, pyrrolidinyl, piperidyl, piperazinyl or pyrazolyl, optionally substituted with a methyl group.

In a preferred embodiment of the invention, A is selected from pyrazolyl optionally substituted with one or two C1-C4 alkyl groups. In a preferred embodiment of the invention, Q1 is * -NR8-Q3. In a preferred embodiment of the invention, Q1 is a group selected from, In a preferred embodiment, Q1 is a group 11 13 R12 where R and R are H and is pyridyl or oxadiazolyl optionally substituted with a C1-C4 alkyl group. The following group of compounds of formula (1) is more preferred: where the group (CH2) n-C (= O) Q1 is in the position meta or para, R1 and R2 are independently selected from H and alkyl C1-C4, - n is 0, 1 or 2 and - Q1 is a group selected from, and a group * -NR8-Q2-A, where p is 1 or 2, Q2 is a C1-C4 alkylene, R8 is H or C1-C4 alkyl and A is pyridyl, C3-C10 cycloalkyl, said cycloalkyl being optionally linked with 1, 2, 3 or 4 carbon atoms, preferably 1 or 2 carbon atoms, tetrahydropyranyl, piperidinyl, tetrahydrothiopyranyl or a group - R3, R4, R5, R6 and R7 are the same or different and are selected from H, C1-C4 alkyl, OR9, SR9, SOR9, SO2R9, halo, CN, CF3, OCF3) SO2NR9R10, COOR9, CONR9R10, NR9R10, NHCOR10 and phenyl optionally substituted with OH; - R9 and R10 are the same or different and are selected from H or C1-C4 alkyl and, - * represents the point of attachment to the carbonyl group; or, if appropriate, their pharmaceutically acceptable salts and / or isomers, tautomers, solvates or isotopic variations thereof. Preferred are compounds of formula (1) which contain the substituents indicated below: Preferably Q1 is a group * -NH-Q2-A, where A is cyclopropyl, cyclohexyl, cycloheptyl or adamantyl. More preferably Q1 is a group * -NH-Q2-A, where A is cyclohexyl or adamantyl. Preferably, A is naphthyl optionally substituted with OR 9. Preferably R8 is H or CH3. More preferably, R8 is H Preferably, Q1 is where R3, R4, R5 and Re are H. Preferably, Q1 is a group * -NH-Q2-A, where A is a group where R3, R4, R5, R6 and R7 are the same or different and are selected from H, C1-C4 alkyl, OR9, SR9, halo, CN, CF3, OCF3, SO2NR9R10, COOR9, CONR9R10, NR9R10, NHCOR10 and optionally substituted phenyl with OH, with the proviso that at least 2 of R3 to R7 are equal to H; where R9 and R1c are the same or different and are selected from H or C1-C4 alkyl. More preferably, Q1 is a group * -NH-Q -A, where A is a group where R3, R4, R5, Rd and R7 are the same or different and are selected from H, CH3, OCH3, OCH2-CH3, SCH3, halo, CF3, with the proviso that at least 2 of R3 to R7 are equal to H In the above group of compounds, the following substitutes are preferred: Q2 is -CH2-, - (CH2) 2-, - (CH2) 3-, -CH (CH3) -, -CH2CH ( CH3) - or (CH (CH3) 2) -, preferably -CH2-. R1 is H or C1-C4 alkyl and R2 is C1-C4 alkyl. More preferably, R1 is H or CH3 and R2 is CH3. n is 1. R1 is H and R2 is CH3 and n is 1.

R1 is CH3, R2 is CH3 and n is 1. The following compounds are preferred, which can be prepared according to the processes described herein:? / - benzyl-2- [3- (2-. {[2- ( 3,5-dihydroxyphenyl) -2-hydroxyethyl-3-amino} -2-methylpropi ') phenyl] acetamide; ? / - cyclopropyl-2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino] -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenylj-N-KIR ^ SJ ^ -hydroxymethi cyclohexyl-acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (3-morpholine-4-) ilpropyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenylj-N-Ípyridin ^ -ylmethyl acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] - / V- (2-morpholin-4-ylethyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - isopropylacetamide; ? / - (4-chlorobenzyl) -2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - [2- (dimethylamino) ethyl ] acetamide; ? / - [2- (diethylamino) ethyl] -2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] Not me} -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [3- (dimethylamino) propyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - pentylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (2-pyrrolidin-1-ylethyl) acetamide; / V- (2,4-dichlorobenzyl) -2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] acetamide; ? / - (3,4-dichlorobenzyl) -2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (4-methoxybenzyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (2-hydroxyethyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - propylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2- (methylpropyl) phenyl] -? / - (3-methoxypropyl) acetamide; / -cyclobutyl-2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} - 2-methylpropyl) phenyl] acetamide; 2- [3- (2- {[[2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - [(1 R) -1 - (1 -naphthyl) ethyl] acetamide; ? / - 2,3-Dihydro-1H-inden-1-yl-2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2- methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxy-phenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - [2- (1-methylpyrrolidine -2-yl) ethyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-) methylpropyl) phenyl] -? / - (4-fluorobenzyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (4-phenylbutyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (3-methoxybenzyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (3-ethoxypropyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (3,4,5- trimethoxybenzyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [4- (trifluoromethyl) ) benzyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - [2- (trifluoromethyl) ) benzyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (3,5- dimethoxybenzyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (2-phenoxyethyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 S) -2-hydroxy -1-methyl ethyl ketamine; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 S) -1- ( hydroxymethyl) -2-methylpropyl] acetamide; 2- [3- (2- { [2- (3,5-d.hydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpro? Il) phenyl] -? / - [(1 S, 2S) -1- (hydroxymethyl) -2-methylbutyl] acetamide; ? / - [(1R?) -1-Benzyl-2-hydroxyethyl] -2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2 -methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1R) -1- (hydroxymethyl) ) propyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 S) -1 - ( hydroxymethyl) -2,2-dimethylpropyl] acetamide; ? / - [(1S) -2-cyclohexyl-1- (hydroxymethyl) ethyl] -2- [3- (2 { [2- (3,5-dihydrophenyl) -2-hydroxyethyl] ] amino.} -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 S, 2) -2 -hydroxy-2,3-dihydro-1H-inden-1-yl-acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (2-propoxyethyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (4-hydroxycyclohexyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (3-propoxypropyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - ethyl -? / - (2-hydroxyethyl) acetamide; 1-. { [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetyl} pperidine-4-carboxamide; 5-. { 2 - [(2- {3- [2- (4-acetylpiperazin-1-yl) -2-oxoethyl] phenyl} -1, 1 -dimethylethyl) amino] -1-hydroxyethyl} benzene-1, 3-diol; 5-. { 2 - [(2- {3- [2- (3,4-dihydroisoquinolin-2 (1 H) -yl) -2-oxoethyl] phenyl} -1, 1-dimethylethyl) amino] -1-hydroxyethyl } benzene-1, 3-diol; ? / - benzyl-2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - methylacetamide; 5- (1-hydroxy-2- { [2- (3- { 2- [4- (2-hydroxyethyl) piperazin-1-yl] -2-oxoethyl}. Phenyl) -1, 1 -dimethylethyl] amino.} ethyl) benzene-1,3-diol; 5- (2- { [2- (3- { 2- [4- (4-chlorophenyl) -4-hydroxypiperidin-1-yl] -2-oxoethyl} phenyl) -1,1 -dimethylethyl] amino.} -1-hydroxyethyl) benzene-1,3-diol; 5-. { 2 - [(1,1-dimethyl-2- { 3- [2- (4-methyl-piperazin-1-yl) -2-oxo-ethyl] -phenyl} -ethyl) -amino] -1-hydroxyethyl} benzene-1,3-diol; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - methyl -? / - (2-phenylethyl) acetamide; 5-. { 2 - [(1,1-dimethyl-2- { 3- [2-oxo-2- (4-pyridin-2-ylpiperazin-1-yl) ethyl] phenyl} ethyl) amino] -1- hydroxyethyl} benzene-1, 3-diol; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - [3- (dimethylamino) propyl] -? / - methylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (2-hydroxyethyl) -? / - propylacetamide; ? / - [2- (diethylamino) ethyl] -2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] - ? / - methylacetamide; 5-. { 2 - [(1, 1 -dimetll-2- { 3- [2- (4-methyl-1,4-diazepan-1-yl) -2-oxoethyl] phenyl} ethyl) amino] -1 -hydroxyethyl} benzene-1, 3-diol; 5- [2- ( { 1, 1-dimethyl-2- [3- (2-morpholin-4-yl-2-oxoethyl) phenyl] ethyl} amino) -1-hydroxyethyl] benzene-1, 3-diol; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - methyl-N - [(1 S) -1-phenylethyljacetamide; 5- [2- ( { 1, 1-dimethyl-2- [3- (2-oxo-2-piperidin-1-ylethyl) phenyl] ethyl} amino) -1-hydroxyethyl) benzene-1, 3-diol; 5- (1-hydroxy-2- { [2- (3 { 2 - [(3 /?) - 3-hydroxypyrrolidin-1-yl] -2-oxoethyl}. Phenyl) - 1, 1-dimethylethyl] amino.} Ethyl) benzene-1,3-diol; d-yl-hydroxy ^ -IP-YS ^ - ^ -S-hydroxypiperidin-l-ylj ^ -oxoethyl} phenyl) -1, 1 -dimethylethyl] amino} ethyl) benzene-1,3-diol; 5-. { 2 - [(2- {3- [2- (4-acetyl-1,4-diazepan-1-yl) -2-oxoethyl] phenyl} -1,1-dimethylethyl) amino] -1 -hydroxyethyl} benzene-1, 3-diol; 5- (1-hydroxy-2- { [2- (3- { 2- [4- (hydroxymethyl) piperidin-1-yl] -2-oxoethyl] phenyl) -1,1 -dimethylethyl] amino.} et.l) benzene-1,3-diol; ? / - (1- { [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpro- pil) phenyl] acetyl} pyrrolidin-3-yl) - / V-methylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] - / V- (2-methoxyethyl) -? / - propylacetamide; 2- [3- (2- { [2- (3,5-dihydroxy-phenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - ethyl -? / - (2-methoxyethyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [3- (dimethylamino) -2, 2-dimethylpropyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [3-fluoro-5- (trifluoromethyl) ) benzyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1S) -1- (hydroxymethyl) ) -3-methylbutyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 S) -2-hydroxy -1-phenylethyl-acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -N,? / - diethylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpro? Il) phenyl] -? / - 1 - / -pyrazol-5-ylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] - / V- (5-methyl-) 1H-pyrazol-3-yl) acetamide; ? / - (cyclohexylmethyl) -2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino] -2-methylpropyl) phenyl] acetamide; 4-. { [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] acetyl} ethyl piperazin-1-carboxylate; N- (5-Chloropyridin-2-yl) -2- [3- (2- { [2- (315-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3I5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (6-methylpyridin-2-yl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (3-methylpyridin-2-yl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - isoquinolin-1-ylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (4,6-dimethylpyridin- 2-yl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxy-phenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] - / V- (2-methoxybenzyl) acetamide; ? / - [(1S) -1-benzyl-2-hydroxyethyl] -2- [3- (2 { [2- (3,5-dihydroxy-phenyl) -2-hydroxyethyl] amino}. 2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (1-ethyl-1 / - / -pyrazol-5-yl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (1,3-dimethyl-1 H -pyrazol-5-yl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (3-fluorobenzyl) acetamide; 1-. { [3- (2- { [2- (3,5-dihydroxy-phenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] acetyl} -L-prolinamide; 5-. { 2 - [(2- {3- [2- (5-amino-3-tert-butyl-1H-pyrazol-1-yl) -2-oxoethyl] phenyl} -1, 1- (methylethyl) amino] -1-hydroxyethyl.} benzene-1,3-diol; 2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2- methylpropyl) phenyl] - / V - [(1 S) -1-phenylethylketamide; 5- { 2 - [(2- {3- [2- (1,4-dioxa-8-azaspiro [4, 5] dec-8-yl) -2-oxoethyl] phenyl] -1, 1-dimethylethyl) amino] -1-hydroxyethyl}. Benzene-1,3-diol;? / - [2- (4- Chloro-phenyl) -ethyl] -3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -benzamide;? / - Adamantan -1-yl-2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.] -? / - [2- (3-fluoro-phenyl) -ethyl] -benzamide; / V- [2- (2-Chloro-phenyl) -ethyl] -3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxr-ethylamino] -2-methyl-propyl} .benzamide; 3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} -? / - [2- (2,3 -dimethyl-phenyl) -ethyl] -benzamide;? / - [2- (2-Chloro-4-fluoro-phenyl) -ethyl] -3-. { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -2-methyl-propyl} -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenol) -2-hydroxy-ethylamino] -2-methyl-propyl} -? / - [2- (4-methoxy-2,3-dimethyl-phenyl) -ethyl] -benzamide; ? / - (3,4-Dichloro-benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethyl- mino] -2-methyl-propyl} phenyl) -acetamide; ? / - (3,4-Dichloro-benzyl) -3-. { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -benzamide; ? / - (4-Chloro-benzyl) -3-. { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -benzamide; ? / - Adamantan-1-il-3-. { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -benzamide; ? / - (4-Chloro-benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino} -2-methyl-propyl} .phenyl) -acetamide; ? / - (4-Trifluoromethoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -2-methyl-propyl.} - phenyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - pyridin-2-yl -methyl-acetamide; ? / - (3,4-Dichloro-benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl ) -acetamide; N- (Benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; ? / - Cyclohexylmethyl-2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; 1- (3,4-Dihydro-1r -soquinolin-2-yl) -2- (3- { 2- [2- (3,5-d.hydroxy-phenyl) -2-hydroxyethylamino] -propyl .}.-phenyl) -ethanone; / -Benzyl-2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] - propyl} phenyl) -? / - methyl acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - (2-hydroxy-benzyl) -acetamide; ? / - (4-Cyano-benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl .}.-phenyl) -acetamide; ? / - (2,4-Dichloro-benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} .-phenyl) -acetamide; / V- (Benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methylpropyl.} - phenyl) -acetamide; ? / - (2-Chlorobenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino} -2-methyl-propyl} - phenyl) -acetamide; ? / - (3-Methoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} .phenyl) -acetamide; ? / - (Cyclohexylmethyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -phenyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - phenethyl-acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (4-chlorophenethyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (4-phenylphenethyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) - / V- (4'-hydroxy-biphenyl-3-ylmethyl) -acetamide; ? / - Cycloheptyl-2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -phenyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - phenethyl-acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) - / V- (2-methylsulfanyl-benzyl) -acetamide; ? / - (2,6-Dichloro-benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} - phenyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - indan-2-yl-acetamide; ? / - (2-Chloro-6-fluorobenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -propyl} -phenyl) -acetamide; / V- (4-Chlorobenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; ? / - (2,5-Dichloro-benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino} -2-methyl-propyl} .phenyl) -acetamide; ? / - (3,5-Dichloro-benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} .phenyl) -acetamide; ? / - (2,6-Dichloro-benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino} -2-methyl-propyl} .phenyl) -acetamide; ? / - Biphenyl-2-ylmethyl-2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethyl- mino] -2-methyl-propyl} phenyl) -acetamide; ? / - (2-Chlorobenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) - acetamide; ? / - (3-Methoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; ? / - (3-Trifluoromethylbenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} - phenyl) -acetamide; ? / - (3,4-Difluorobenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; ? / - (2-Methoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; ? / - (3,4-Dimethylbenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; ? / - (3,4-Dimethoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; 4-. { [2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetylamino] -methyl} -benzamide; 2- (3- { 2- [2- (3,5-D-Hydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - indan-1 - il-acetamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (3-fluorophenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-D-Hydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2- chlorophenyl) -ethyl] -benzamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - naphthalen-1-methylmethyl-acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - (2-fluoro-5-trifluoromethyl- benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) - / V- (3-chlorobenzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - (4-fluoro- 3-trifluoromethyl-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (2-methylsulfanyl- benzyl) -acetamide; 4-. { [2- (3- { 2- [2- (3,5-D-Hydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -phenyl) -acetylamino] -methyl} -benzamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) - / - (4-sulfamoyl) -benzyl) -acetamide; Methyl ester of 4- acid. { [2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -phenyl) -acetylamino] -methyl} -benzoic; V- (1-Benzyl-piperidin-4-yl) -2- (3. {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl}-phenyl) -acetamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2-phenethyl-benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (5- fluoro-2-methyl-phenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} - / V- [2- (2-trifluoromethyl-phenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - (2-naphthalen-1-yl-ethyl) -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2, 4,5-trimethyl-phenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2,3-dimethyl-phenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} - / V- [2- (2-hydroxy-3-chloro-phenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (4-chlorophenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-D-Hydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -V- [2- (2-hydroxy-5-chloro-phenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2-Chloro-4-fluoro-phenyl) -ethyl] -benzamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (2-methyl- benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (3-methyl- benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (4-methyl-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (2-methoxy) benzyl) -acetamide 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - ( 4-methoxy-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (2, 3- d imethyl-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -N- (3,4 -dimethyl-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - ( 2-chloro-6-methyl-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (3- chloro-4-methyl-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - [2- (6 -methoxy-naphthalen-2-yl) -ethyl] -acetamide; ? / - (2-Chlorobenzyl) -3- (3- {2- [2- (3,5-dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) propionamide; ? / - (2,6-D-chlorobenzyl) -3- (3- {2- [2- (3,5-dihydroxyphenyl) -2-hydroxy-thylamino] propyl} phenyl) propionamide; * 1- (3,4-Dihydro-1H-isoquinolin-2-yl) -3- (3- {2- [2- (3,5-dihydroxyphenyl) -2-hydroxyethylamino] propyl}. phenyl) propan-1-one; ? / - (2-Chloro-4-fluorobenzyl) -2- (3- { 2- [2- (3,5-dihydroxyphenyl) -2-hydro- xytylamino] propyl} phenyl) acetamide; ? / - (4-Bromobenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -2-methylpropyl} phenyl acetamide; 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] -2-methylpropyl}. Phenyl) - / V- (3,4-d.methylphenyl) acetamide; 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) -? / - (2,3-dimethylbenzyl) acetamide; 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) -? / - (4-fluorobenzyl) acetamide; 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) -1- (4-pyridin-2-ylpiperazin-1-yl) ethanone; and, 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] -2-methylpropyl.} phenyl) -? / - (2-phenylpropyl) acetamide. According to one aspect of the present invention, compounds of formula (1) in which the (CH2) n-C (= O) Q1 group is in the meta position are generally preferred. The pharmaceutically acceptable salts of the compounds of formula (1) include the acid addition salts and base addition salts thereof. Suitable acid addition salts are formed from acids that form non-toxic salts. Examples include acetate, adipate, aspartate, benzoate, besylate, bicarbonate / carbonate, bisulfate salts to / sulfate, borate, camsylate, citrate, cyclamate, edisilate, esylate, formate, fumarate, gluceptate, gluconate, glucuronate, hexafluorophosphate, hybienate, hydrochloride / chloride, hydrobromide / bromide, hydroiodide / iodide, hydrogen phosphate, isethionate, D- and L-lactate, malate, maleate, malonate, mesylate, methylsulfate, 2-napsylate, nicotinate, nitrate, orotate, oxalate, palmitate, pamoate, phosphate / hydrogen, phosphate / dihydrogen phosphate, pyroglutamate, saccharate, stearate, succinate, tannate, D - and L-tartrate, 1-hydroxy-2-naphthoate, tosylate and xinafoate. Suitable basic salts are formed from bases that form non-toxic salts. Examples include aluminum salts, arginine, benzathine, calcium, choline, diethylamine, diolamine, glycine, lysine, magnesium, meglumine, olamine, potassium, sodium, tromethamine and zinc. Hemisal acids and bases can also be formed, for example, hemisulfate and hemicalcium salts. For a review of the appropriate salts, see "Handbook of Pharmaceutical Salts: Properties, Selection, and Use ", by Stahl and Wermuth (Wiley-VCH, Weinheim, Germany, 2002) The pharmaceutically acceptable salts of the compounds of formula (1) can be prepared by one or more of three methods: i) by reacting the compound of formula (1) with the desired acid or base, (ii) removing an acid-labile protecting group or bases from a suitable precursor of the compound of formula (1) or by opening the ring of a suitable cyclic precursor, for example, a lactone or lactam, using the desired acid or base; or (ii) converting a salt of the compound of formula (1) in another by reaction with an appropriate acid or base or by means of a suitable ion exchange column. The three reactions are typically performed in solution. The resulting salt can be precipitated and collected by filtration or can be recovered by evaporation of the solvent. The degree of ionization of the resulting salt can vary from completely ionized to almost non-ionized. The compounds of the invention can exist in both unsolvated and solvated forms. The term "solvate" is used herein to describe a molecular complex comprising the compound of the invention and a stoichiometric amount of one or more pharmaceutically acceptable solvent molecules., for example, ethanol. The term "hydrate" is used when said solvent is water. Within the scope of the invention are included complexes, such as clathrates, drug-host inclusion complexes in which, unlike what occurs with the solvates mentioned above, the drug and the host molecule are present in stoichiometric amounts or not stoichiometric Also included are drug complexes containing two or more organic components and / or inorganic which may be in stoichiometric or non-stoichiometric amounts. The resulting complexes can be ionized, partially ionized or non-ionized. As a review of such complexes, see J Pharm Sci, 64 (8), 1269-1288 of Haleblian (August, 1975). Hereinafter, all references to the compounds of formula (1) include references to salts, solvates and complexes thereof and to solvates and salt complexes thereof. The compounds of the invention include compounds of formula (1) as defined hereinabove, including all polymorphs and crystalline habits thereof, prodrugs and isomers thereof (including optical, geometric and tautomeric isomers) as defined later in this document, and compounds labeled with isotopes of formula (1). As indicated, so-called "prodrugs" of the compounds of formula (1) are also within the scope of the invention. In this way, certain derivatives of the compounds of formula (1) which may have little or no pharmacological activity by themselves, when administered in or on the body, can be converted to compounds of formula (1) with the desired activity, for example , by hydrolytic cleavage. Such derivatives are referred to as "prodrugs". Additional information on the use of prodrugs can be found in 'Pro-drugs as Novel Delivery Systems, Vol. 14, ACS Symposium Series (T. Higuchi and W. Stella) and 'Bioreversible Carriers in Drug Design', Pergamon Press, 1987 (ed. E. B. Roche, American Pharmaceutical Association). Prodrugs according to the invention can be produced, for example, by replacing appropriate functionalities present in the compounds of formula (1) with certain residues that those skilled in the art know as 'pro-residues' as described, for example, in " Design of Prodrugs "by H. Bundgaard (Elsevier, 1985). Some examples of prodrugs according to the invention include: (i) those in which the compound of formula (1) contains a carboxylic acid functionality (-COOH), or an ester thereof, for example, a compound in which the hydrogen of the carboxylic acid functionality of the compound of formula (1) is replaced with alkyl (Ci-Cß); (ii) those in which the compound of formula (1) contains an alcohol functionality (-OH), or an ester thereof, for example, a compound in which the hydrogen of the alcohol functionality of the compound of formula (1) it is replaced by alkanoyloxymethyl (Ci-Cß); and (ii) those in which the compound of formula (1) contains a primary or secondary amino functionality (-NH2 or -NHR, where R? H), or an amide thereof, for example, a compound in which , as the case may be, one or both of the hydrogens of the amino functionality of the compound of formula (1) are replaced by (C1-C10) alkanoyl; In the references mentioned above, other examples of replacement groups can be found according to the previous examples and other examples of prodrug types. In addition, certain compounds of formula (1) can act by themselves as prodrugs of other compounds of formula (1). Also included within the scope of the invention are metabolites of compounds of formula (1), ie, compounds formed in vivo after drug administration. Some examples of metabolites according to the invention include: (i) those in which the compound of formula (1) contains a methyl group, or a hydroxymethyl derivative thereof (-CH 3 - »-CH 2 OH); (ii) those in which the compound of formula (1) contains an alkoxy group, or a hydroxy derivative thereof (-OR - »-OH); those in which the compound of formula (1) contains a tertiary amino group, or a secondary amino derivative thereof (-NR1R2 - »-NHR1 p -NHR2); (iv) those in which the compound of formula (1) contains a secondary amino group, or a primary derivative thereof (-NHR1 - »-NH2); (v) those in which the compound of formula (1) contains a phenyl residue, or a phenol derivative thereof (-Ph - »-PhOH); and (vi) those in which the compound of formula (1) contains an amide group, or a carboxylic acid derivative thereof (-CONH2 - -COOH).

The compounds of formula (1) containing one or more asymmetric carbon atoms can exist as two or more stereoisomers. When a compound of formula (1) contains an alkenyl or alkenylene group, the cis / trans (or Z / E) geometric isomers are possible. When the structural isomers are interconvertible by means of a low energy barrier, tautomeric isomerism ("tautomerism") may exist. This can take the form of proton tautomerism in compounds of formula (1) containing, for example, an imino, keto or oxime group, or of the so-called valence tautomerism in compounds containing an aromatic moiety. From this it follows that a single compound can have more than one type of isomerism. Within the scope of the present invention are included all stereoisomers, geometric isomers and tautomeric forms of the compounds of formula (1), including compounds that display more than one type of isomerism, and mixtures of one or more thereof. Also included are acid addition salts or bases in which the counterion is optically active, for example, d-lactate or / -lysine, or racemic, for example aV-tartrate or oV-arginine. The cis / trans isomers can be separated by conventional techniques well known to those skilled in the art, for example, chromatography and fractional crystallization. Conventional techniques for the preparation / isolation of Individual enantiomers include chiral synthesis from a suitable optically pure precursor or resolution of the racemate (or the racemate of a salt or derivative) using, for example, chiral high pressure liquid chromatography (HPLC). Alternatively, the racemate (or a racemic precursor) can be reacted with a suitable optically active compound, for example, an alcohol or, in case the compound of formula (1) contains an acid or basic moiety, an acid or base such as tartaric acid or 1-phenylethylamine. The resulting diastereomeric mixture can be separated by chromatography and / or fractional crystallization and one or both of the diastereoisomers can be converted to the corresponding pure enantiomers by means well known to those skilled in the art. The chiral compounds of the invention (and their chiral precursors) can be obtained in enantiomerically enriched form using chromatography, typically HPLC, on an asymmetric resin with a mobile phase consisting of a hydrocarbon, typically heptane or hexane, containing 0 to 50% in volume of isopropanol, typically from 2% to 20%, and from 0 to 5% by volume of an alkylamine, typically 0.1% of diethylamine. The concentration of the eluate produces the enriched mixture. Stereoisomeric conglomerates can be separated by conventional techniques known to those skilled in the art - see, for example, "Stereochemistry of Organic Compounds" by E.L. Eliel (Wiley, New York, 1994). According to one aspect of the present invention, the stereoisomer (R, R) of the formula given below is generally preferred, wherein R 1 is hydrogen and R 2 is C 1 -C 4 alkyl, preferably methyl, and n and Q 1 are as have been previously defined: The present invention includes all pharmaceutically acceptable isotope-labeled compounds of formula (1) in which one or more atoms have been replaced by atoms having the same atomic number but an atomic mass or atomic number other than the atomic mass or atomic number that predominates in nature. Examples of suitable isotopes for inclusion in the compounds of the invention include isotopes of hydrogen, such as 2H and 3H, carbon, such as 11C, 13C and 14C, chloro, such as 36CI, fluorine, such 1fi 123 12 * 5 13 15 as F, iodine, such as I and I, nitrogen, such as N and N, oxygen, such as 15O, 17O and 18O, phosphorus, such as 32P and sulfur, such as 35S. Certain compounds labeled with isotopes of formula (1), for example, those that incorporate a radioactive isotope, are useful in studies of distribution of drugs and / or substrates in tissues. The radioactive isotopes tritium, that is, 3H, and carbon 14, that is, 14C, are particularly useful for this purpose thanks to their easy incorporation and detection. Substitution with heavier isotopes such as deuterium, ie, 2H, may produce certain therapeutic advantages as a result of increased metabolic stability, for example, longer half-life in vivo or the need for lower dosage and, therefore, may prefer in some circumstances. Substitution with positron emitting isotopes, such as 11C, 18F, 15O and 13N, may be useful in Positron Emission Topography (PET) studies to examine the occupation of substrate receptors. The isotope-labeled compounds of formula (1) can be prepared generally by conventional techniques known to those skilled in the art or by processes analogous to those described in the accompanying Examples and Preparations using appropriate isotope-labeled reagents in place of the unlabelled reagent previously employed . The pharmaceutically acceptable solvates according to the invention include those in which the crystallization solvent can be substituted isotopically, for example, D2O, d-acetone or d-DMSO. The compounds of formula (1), their pharmaceutically acceptable salts and / or their derivative forms are valuable pharmaceutically active compounds, which are suitable for the therapy and prophylaxis of numerous disorders in which the β2 receptor is involved or in which the agonism of this receptor can induce some benefit, in particular in allergic and non-allergic diseases of the respiratory tract, but also in the treatment of other diseases such as, but not limited to , those of the nervous system, premature birth, congestive heart failure, depression, inflammatory and allergic diseases of the skin, psoriasis, proliferative skin diseases, glaucoma and in conditions in which it is positive to reduce gastric acidity, particularly in gastric ulcers and peptic The compounds of the invention intended for pharmaceutical use can be administered as crystalline or amorphous products. They can be obtained, for example, as solid plugs, powders or films, by methods such as precipitation, crystallization, lyophilization, spray drying or evaporative drying. For this purpose, microwave or radiofrequency drying can be used. The compounds of the invention can be administered alone or in combination with one or more other compounds of the invention or in combination with one or more other drugs (or as any combination thereof). Generally, they will be administered as a formulation together with one or more pharmaceutically acceptable excipients. The term "excipient" is used herein to describe any ingredient other than the compound or compounds of the invention. The chose of the excipient will largely depend on factors such as the particular mode of administration, the effect of the excipient on solubility and stability, and the nature of the dosage form. Pharmaceutical compositions suitable for the administration of compounds of the present invention and methods for their preparation will be apparent to those skilled in the art. Such compositions and methods for their preparation can be found, for example, in "Remington's Pharmaceutical Sciences," 19th Edition (Mack Publishing Company, 1995) The compounds of the invention can be administered orally, oral administration can involve swallowing, so that the compound enters the gastrointestinal tract, or buccal or sublingual administration can be employed, whereby the compound enters directly into the bloodstream from the mouth.Well formulations suitable for oral administration include solid formulations such as tablets, capsules that Contain particles, liquids or powders, dragees (including liquid-filled ones), chewable, multi- and nano-particles, gels, solid solutions, liposomes, films, ovules, sprays and liquid formulations.The liquid formulations include suspensions, solutions, syrups and elixirs, such formulations can be used as capsule fillers hard or soft cells and typically comprise a vehicle, for example, water, ethanol, polyethylene glycol, propylene glycol, methylcellulose or a suitable oil, and one or more emulsifying agents and / or suspending agents. Liquid formulations can also be prepared by reconstituting a solid, for example, in an envelope. The compounds of the invention can also be used in rapidly dissolving and rapidly disintegrating dosage forms such as those described in Expert Opinion in Therapeutic Patents, 11 (6), 981-986, by Liang and Chen (2001). For dosage forms in tablets, depending on the dose, the drug can be from 1% by weight to 80% by weight of the dosage form, more typly from 5% by weight to 60% by weight of the dosage form. In addition to the drug, the tablets generally contain a disintegrant. Examples of disintegrants include sodium starch glycolate, sodium carboxymethylcellulose, calcium carboxymethylcellulose, croscarmellose sodium, crospovidone, polyvinylpyrrolidone, methylcellulose, microcrystalline cellulose, hydroxypropyl cellulose substituted with lower alkyl, starch, pregelatinized starch and sodium alginate. Generally, the disintegrant will constitute from 1% by weight to 25% by weight, preferably from 5% by weight to 20% by weight of the dosage form. Binders are generally used to impart cohesive qualities to a tablet formulation. Suitable binders include microcrystalline cellulose, gelatin, sugars, polyethylene glycol, gums natural and synthetic, polyvinylpyrrolidone, pregelatinized starch, hydroxypropylcellulose and hydroxypropylmethylcellulose. The tablets may also contain diluents such as lactose (monohydrate, spray-dried monohydrate, anhydrous and the like), mannitol, xylitol, dextrose, sucrose, microcrystalline cellulose, starch and dibasic calcium phosphate dihydrate. The tablets may also optionally contain surfactants such as sodium lauryl sulfate and polysorbate 80, and glidants such as silicon dioxide and talc. When present, the surfactants may constitute 0.2 wt% to 5 wt%, and the glidants may constitute 0.2 wt% to 1 wt% of the tablet. The tablets also generally contain lubrts such as magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate and mixtures of magnesium stearate with sodium lauryl sulfate. The lubrts generally constitute from 0.25% by weight to 10% by weight, preferably from 0.5% by weight to 3% by weight of the tablet. Other possible ingredients include anti-oxidants, colorants, flavors, preservatives and flavor masking agents. Illustrative tablets contain up to about 80% of drug, from about 10% by weight to about 90% by weight of binder, from about 0% by weight to about 85% by weight of diluent, from about 2% by weight to about 10% by weight of disintegrant and of about 0.25% by weight to about 10% by weight of lubrt. The tablet mixtures can be compressed directly or with a roller to form tablets. Alternatively, mixtures of tablets or portions of mixtures may be wet granulated, dry or melt, coagulated in the molten state, or extruded prior to tableting. The final formulation may comprise one or more layers and may be coated or uncoated; it may even be encapsulated. Tablet formulation is described in Pharmaceut Dosage Forms: Tablets, Vol. 1, by H. Lieberman and L. Lachman, Marcel Dekker, New York, 1980. Oral films consumable for human or veterinary use are typly film dosage forms. thin soluble or swellable in water which can be fast-dissolving or mucoadhesive and typly comprise a compound of formula I, a film-forming polymer, a binder, a solvent, a humectant, a plasticizer, a stabilizer or emulsifier, an agent for modifying the viscosity and a solvent. Some components of the formulation can perform more than one function. The compound of formula (1) can be soluble or insoluble in water. A water-soluble compound typically comprises from 1% by weight to 80% by weight, more typically from 20% by weight to 50% by weight of the solutes. Less soluble compounds can comprise a greater proportion of the composition, typically up to 88% by weight of the solutes.

Alternatively, the compound of formula (1) may be in the form of multiparticulate beads. The film forming polymer can be selected from natural polysaccharides, proteins or synthetic hydrocolloids, and is typically present in the range of 0.01 to 99% by weight, more typically in the range of 30 to 80% by weight. Other possible ingredients include anti-oxidants, colorants, flavors and flavor enhancers, preservatives, salivary stimulating agents, cooling agents, co-d solvents (including oils), emollients, bulking agents, anti-foaming agents, surfactants and agents to mask the taste. The films according to the invention are typically prepared by drying with evaporation of thin aqueous films applied as a coating on a releasable paper or support. This can be done in a drying oven or tunnel, typically a combined coater or by lyophilization or vacuum treatment. Solid formulations for oral administration can be formulated to be immediate and / or modified release. Modified release formulations include delayed, sustained, pulsed, controlled, directed and programmed release. US Pat. No. 6,106,864 describes modified release formulations suitable for the purposes of invention. In Pharmaceutical Technology On-line, 25 (2), 1-14 (2001) from Verma et al (2001) one can find details of other suitable release technologies such as high energy dispersions, osmotic and coated particles. In WO 00/35298 the use of chewing gum is described to achieve a controlled release. The compounds of the invention can also be administered directly to the bloodstream, to the muscle or to an internal organ. Suitable means for parenteral administration include intravenous, intraarterial, intraperitoneal, intrathecal, intraventricular, intraurethral, intrasternal, intracranial, intramuscular and subcutaneous administration. Suitable devices for parenteral administration include needle injectors (including microneedles), needleless injectors and infusion techniques. Parenteral formulations are typically aqueous solutions which may contain excipients such as salts, carbohydrates and buffering agents (preferably at a pH of 3 to 9) but, for some applications, may be formulated more adequately as a sterile non-aqueous solution or as a dry form to be used together with a suitable vehicle such as sterile pyrogen-free water. The preparation of parenteral formulations under sterile conditions, for example, by lyophilization, can be easily achieved using conventional pharmaceutical techniques well known to those skilled in the art.

The technique. The solubility of the compounds of formula (1) used in the preparation of parenteral solutions can be increased by the use of appropriate formulation techniques, such as the incorporation of agents that improve solubility. Formulations for parenteral administration can be formulated to be immediate and / or modified release. Modified release formulations include delayed, sustained, pulsed, controlled, directed and programmed release. In this way, the compounds of the invention can be formulated as a solid, semi-solid or thixotropic liquid for administration as an implanted reservoir that provides a modified release of the active compound. Examples of such formulations include drug-coated stents and poly (d / -lactic-glycolic acid) (PGLA) microspheres. The compounds of the invention can also be administered topically to the skin or mucosa, that is, dermally or transdermally. Typical formulations for this purpose include gels, hydrogels, lotions, solutions, creams, ointments, fine powders, dressings, foams, films, skin patches, wafers, implants, sponges, fibers, bandages and microemulsions. Liposomes can also be used. Typical vehicles include alcohol, water, mineral oil, liquid petrolatum, white petrolatum, glycerin, polyethylene glycol and propylene glycol. Agents can be incorporated improve penetration - see, for example, J Pharm Sci, 88 (10), 955-958 by Finnin and Morgan (October 1999). Other means of topical administration include administration by electroporation, iontophoresis, phonophoresis, sonophoresis, and microneedle or needle-free injection (e.g., Powderject ™, Bioject ™, etc.). Formulations for topical administration can be formulated to be immediate release and / or modified. Modified release formulations include delayed, sustained, pulsed, controlled, directed and programmed release. The compounds of the invention can also be administered intranasally or by inhalation, typically in the form of a dry powder (alone or as a mixture, for example, in a dry mixture with lactose, or as a mixed component particle, for example. mixed with phospholipids, such as phosphatidylcholine) from a dry powder inhaler or as an aerosol spray from a pressurized container, pump, sprayer, atomizer (preferably an atomizer using electrohydrodynamics to produce a fine mist) or nebulizer, with or without the use of a suitable propellant, such as 1,1,1,2-tetrafluoroethane or 1,1,2,3,3,3-heptafluoropropane. For intranasal use, the powder may comprise a bioadhesive agent, for example, chitosan or cyclodextrin. The pressurized container, pump, spray, atomizer or nebulizer contains a solution or suspension of the compound (s) the invention comprising, for example, ethanol, aqueous ethanol or an alternative agent suitable for dispersing, solubilizing or extending the release of the active compound, one or more propellants as a solvent and an optional surfactant, such as sorbitan trioleate, oleic acid or a Oligolactic acid. Before use in a dry powder or suspension formulation, the drug is micronized to a size suitable for administration by inhalation (typically less than 5 microns). This can be achieved by any suitable grinding method, such as in a spiral jet mill, in a fluid bed jet mill, supercritical fluid processing to form nanoparticles, high pressure homogenization or spray drying. Capsules (made, for example, with gelatin or hydroxypropylmethylcellulose), blisters and cartridges for use in an inhaler or insufflator can be formulated to contain a powder mixture of the compound of the invention, a suitable powder base such as lactose or starch and a performance modifier, such as / -leucine, mannitol or magnesium stearate. The lactose may be anhydrous or it may be in the monohydrate form, preferably the latter. Other suitable excipients include dextran, glucose, maltose, sorbitol, xylitol, fructose, sucrose and trehalose. A solution formulation suitable for use in an atomizer using electrohydrodynamics to produce a fine mist can contain from 1 μg to 20 mg of the compound of the invention per actuation and the volume of the action can vary from 1 μl to 100 μl. A typical formulation may comprise a compound of formula (1), propylene glycol, sterile water, ethanol and sodium chloride. Other alternative solvents that can be used in place of propylene glycol include glycerol and polyethylene glycol. Suitable flavors, such as menthol and levomenthol, or sweeteners, such as saccharin or sodium saccharin, can be added to the formulations of the invention intended for inhaled / intranasal administration. Formulations for inhaled / intranasal administration can be formulated to be immediate release and / or modified using, for example, PGLA. Modified release formulations include delayed, sustained, pulsed, controlled, directed and programmed release. In the case of dry powder inhalers and aerosols, the dosage unit is determined by means of a valve that supplies a measured quantity. The units according to the invention are typically arranged to deliver a metered dose or "pulse" containing from 0.001 mg to 10 mg of the compound of formula (1). The total daily dose will typically be in the range of 0.001 mg to 40 mg, which may be administered in a single dose or, more usually, in divided doses throughout the day. The compounds of formula (1) are particularly suitable for administration by inhalation.

The compounds of the invention can be administered rectally or vaginally, for example, in the form of a suppository, pessary or enema. Cocoa butter is a traditional suppository base, but various alternatives may be used as appropriate. Formulations for rectal / vaginal administration can be formulated to be immediate and / or modified release. Modified release formulations include delayed, sustained, pulsed, controlled, directed and programmed release. The compounds of the invention can also be administered directly to the eye or ear, typically in the form of drops of a suspension or micronized solution in sterile isotonic saline with adjusted pH. Other formulations suitable for ocular and aural administration include ointments, biodegradable (e.g., absorbable gel sponge, collagen) and non-biodegradable (e.g. silicone) implants, wafers, lenses and particulate or vesicular systems, such as niosomes or liposomes. A polymer such as crosslinked polyacrylic acid, polyvinyl alcohol, hyaluronic acid, a cellulose polymer, for example, hydroxypropylmethylcellulose, hydroxyethylcellulose or methylcellulose, or a heteropolysaccharide polymer, for example, gellan gum, together with a preservative such as chloride may be incorporated. of benzalkonium. Such formulations can also be administered by iontophoresis. Formulations for ocular / aural administration can formulated to be immediate and / or modified release. Modified release formulations include delayed, sustained, pulsed, controlled, directed and programmed release. The compounds of the invention can be combined with soluble macromolecular entities, such as cyclodextrin and suitable derivatives thereof or polyethylene glycol-containing polymers, to improve their solubility, dissolution rate, taste masking, bioavailability and / or stability for use in any of the modes of administration mentioned above. Drug-cyclodextrin complexes, for example, are generally considered useful for most dosage forms and routes of administration. Inclusion complexes and non-inclusion complexes can be used. As an alternative to the direct formation of complexes with the drug, the cyclodextrin can be used as an auxiliary additive, that is, as a vehicle, diluent or solubilizer. The most commonly used for these purposes are alpha-, beta- and gamma-cyclodextrins, examples of which can be found in International Patent Applications No. WO / 91/11172, WO 94/02518 and WO 98/55148. Whenever it is desirable to administer a combination of active compounds, for example, for the purpose of treating a particular disease or condition, it is within the scope of the present invention that two or more pharmaceutical compositions can conveniently be combined, containing at least one of them a compound according to the invention, in the form of a kit suitable for the co-administration of the compositions. In this way, the kit of the invention comprises two or more different pharmaceutical compositions, of which at least one contains a compound of formula (1) according to the invention, and means for keeping said compositions separate, such as a container, a divided bottle or a divided laminated package. An example of such a kit is the known blister which is used to package tablets, capsules and the like. The kit of the invention is particularly suitable for administering different dosage forms, for example parenteral, for administering the different compositions in different dosage ranges, or for evaluating the different compositions from each other. To improve acceptance, the kit typically contains instructions for administration and can be provided with a so-called reminder. For administration to human patients, the total daily dose of the compounds of the invention is typically in the range of 0.001 mg to 5000 mg depending, of course, on the mode of administration. For example, an intravenous daily dose may only require 0.001 mg to 40 mg. The total daily dose may be administered in a single dose or in divided doses and may, at the discretion of the physician, be outside the typical range provided herein.

These dosages are based on an average human being weighing approximately 65 kg to 70 kg. The doctor can easily determine the doses for subjects whose weights are outside this range, such as children and the elderly. For the avoidance of doubt, the references in this document to "treatment" includes references to curative, palliative and prophylactic treatment. According to another embodiment of the present invention, the compounds of formula (1) or pharmaceutically acceptable salts, derivative forms or compositions thereof, can also be used as a combination with one or more additional therapeutic agents to be co-administered to a patient to obtain some particularly desired therapeutic end result such as the treatment of pathophysiologically significant disease processes including, but not limited to (i) bronchoconstriction, (ii) inflammation, (iii) allergy, (iv) tissue destruction, (v) signs and symptoms such as shortness of breath or cough. The second and the other additional therapeutic agents may also be a compound of formula (1), or a pharmaceutically acceptable salt, derivative forms or compositions thereof, or one or more β2 agonists known in the art. More typically, the second and the other therapeutic agents will be selected from a different class of therapeutic agents. As used in this document, the terms "co- "administration", "co-administered" and "in combination with", when referring to the compounds of formula (1) and one or more other therapeutic agents, is intended to mean, signify and includes the following: • simultaneous administration of such a combination of one or more compounds of formula (1) and one or more therapeutic agents to a patient in need of treatment, when such components are formulated together in a single dosage form that releases said components substantially at the same time in said patient, • administration substantially of such combination of one or more compounds of formula (1) and one or more therapeutic agents to a patient in need of treatment, when such components are formulated separately in different dosage forms that the patient takes substantially at the same time, after which said components are released substantially at the same time in said patient, • secu administration of such a combination of one or more compounds of formula (1) and one or more therapeutic agents to a patient in need of treatment, when such components are formulated separately in separate dosage forms that the patient takes at consecutive times with an interval of significant time between each administration, after which said components are released at substantially different times in said patient, and • sequential administration of such combination of one or more compounds of formula (1) and one or more therapeutic agents to a patient in need of treatment, when such components are formulated together in a single dosage form that releases said components in a controlled manner, after which they are administered concurrently, consecutive and / or overlapping at the same time and / or at different times by said patient, where each part can be administered by the same route or by a different route. Suitable examples of other therapeutic agents that can be used in combination with the compound (s) of formula (1) or pharmaceutically acceptable salts, derivative forms or compositions thereof include, but are not limited to: (a) 5-lipoxygenase inhibitors (5) -LO) or antagonists of the 5-lipoxygenase activation protein (FLAP), (b) Leukotriene antagonists (LTRA), including LTB4, LTC4, LTD4 and LTE4 antagonists, (c) Histamine receptor antagonists, including H1 and H3 antagonists, (d) Sympathomimetic vasoconstrictor agents of adrenoceptor agonists i and a2 for decongestant use, (e) M3 muscarinic receptor antagonists or anticholinergic agents, (f) PDE inhibitors, for example PDE3, PDE4 and PDE5 inhibitors, (g) Theophylline (h) sodium cromoglycate, (i) COX inhibitors, selective and non-selective inhibitors of COX-1 or COX-2 (NSAID) (j) Oral and inhaled glucocorticosteroids, such as DAGR (dissociated corticosteroid receptor agonists) (k) Monoclonal antibodies active against endogenous inflammatory entities, (I) Anti-tumor necrosis factor agents a (anti-TNF-a) (m) Adhesion molecule inhibitors including VLA-4 (n) antagonists Quinine receptor antagonists Bi and B2 (o) Immunosuppressant agents, (p) Matrix metalloprotease inhibitors (MMP) ), (q) Tachykinin receptor antagonists NK1, NK2 and NK3, (r) Elastase inhibitors, (s) Adenosine A2a receptor agonists, (t) Urokinase inhibitors, (u) Compounds that act on the receptors of dopamine, or example D2 agonists, (v) Modulators of the NFkβ pathway, for example inhibitors of IKK, (w) Modulators of cytokine signaling pathways such as p38 MAP kinase or syk kinase, (x) Agents that can be classified as mucolytic or antitussive, and (y) Antibiotics, (z) HDAC inhibitors and (aa) PI3 kinase inhibitors. According to the present invention, the combination of the compounds of formula (1) with: - H3 antagonists, - M3 muscarinic receptor antagonists, - PDE4 inhibitors - Glucocorticosteroids, - Adenosine A2a receptor agonists, - Modulators are preferred. of the cytokine signaling pathway, such as p38 MAP kinase or syk kinase, - Leukotriene antagonists (LTRA) including LTB4, LTC4, LTD and LTE antagonists. In accordance with the present invention, combinations of the compounds of formula (1) with: - glucocorticosteroids, in particular inhaled glucocorticosteroids with few systemic side effects, including prednisone, prednisolone, flunisolide, triamcinolone acetonide, beclomethasone dipropionate, budesonide, fluticasone propionate, ciclesonide and mometasone furoate, or - muscarinic M3 receptor antagonists or anticholinergic agents , including in particular ipratropium salts, particularly bromide, tiotropium salts, particularly bromide, oxitropium salts, particularly bromide, perenzepine and telenzepine. It should be appreciated that all references in this document to treatment include curative, palliative and prophylactic treatment. The description given below relates to the therapeutic applications in which the compounds of formula (1) can be applied. The compounds of formula (1) have the ability to interact with the β2 receptor and, therefore, have a wide range of therapeutic applications, as described further below, given the essential role that the β2 receptor plays in the physiology of all mammals. Therefore, a further aspect of the present invention relates to the compounds of formula (1), or pharmaceutically acceptable salts, derivative forms or compositions thereof, for use in the treatment of diseases, disorders and conditions in which they are present. involved the ß2 receptor. More specifically, the present invention also relates to the compounds of formula (1), or pharmaceutically acceptable salts, derivative forms or compositions thereof, for use in the treatment of diseases, disorders and conditions selected from the group consisting of: asthma of any type, etiology or pathogenesis, in particular asthma which is a member selected from the group consisting of atopic asthma, non-atopic asthma, allergic asthma, bronchial atopic asthma mediated by IgE, bronchial asthma, essential asthma, true asthma, intrinsic asthma caused by pathophysiological alterations, extrinsic asthma caused by environmental factors, essential asthma of unknown or unapparent origin, non-atopic asthma, bronchitic asthma, emphysematous asthma, exercise-induced asthma, allergen-induced asthma, cold-air-induced asthma, occupational asthma, infectious asthma caused by infection by bacteria, fungi, protozoa or viruses, non-allergic asthma, asthma incipient, wheezing syndrome in children and bronchiolitis, • chronic or acute bronchoconstriction, chronic bronchitis, obstruction of the lower respiratory tract and emphysema, • obstructive or inflammatory diseases of the respiratory tract of any type, etiology or pathogenesis, in particular, an obstructive disease or inflammatory of the respiratory tract which is a member selected from the group consisting of eosinophilic pneumonia chronic, chronic obstructive pulmonary disease (COPD), COPD that includes chronic bronchitis, pulmonary emphysema or dyspnea associated or not associated with COPD, COPD characterized by irreversible and progressive obstruction of the respiratory tract, respiratory distress syndrome in adults (ARDS), exacerbation of airway hyperreactivity after therapy with other drugs and respiratory disease associated with pulmonary hypertension, • bronchitis of any kind, etiology or pathogenesis, in particular bronchitis which is a member selected from the group consisting of acute bronchitis , acute laryngotracheal bronchitis, arachidic bronchitis, catarrhal bronchitis, bronchitis with laryngotracheitis, dry bronchitis, infectious asthmatic bronchitis, productive bronchitis, staphylococcal or streptococcal bronchitis and vesicular bronchitis, • acute lung injury, • bronchiectasis of any kind, etiology or pathogenesis nesis, in particular bronchiectasis which is a member selected from the group consisting of cylindrical bronchiectasis, bronchiectasis sacculate, fusiform bronchiectasis, capillary bronchiectasis, cystic bronchiectasis, dry bronchiectasis and follicular bronchiectasis. Another aspect of the present invention also relates to the use of the compounds of formula (1), or pharmaceutically acceptable salts, derivative forms or compositions thereof, for the manufacture of a drug that has a β2 agonist activity. In particular, the present invention relates to the use of the compounds of formula (1), or pharmaceutically acceptable salts, derivative forms or compositions thereof, for the manufacture of a drug for the treatment of diseases and / or conditions mediated by β2 , in particular the diseases and / or conditions listed above. As a consequence, the present invention provides a particularly interesting method for treating a mammal, including a human, with an effective amount of a compound of formula (1), or a pharmaceutically acceptable salt, derivative form or composition thereof. More precisely, the present invention provides a particularly interesting method for the treatment of diseases and / or conditions mediated by β2 in a mammal, including a human being, in particular the diseases and / or conditions listed above, which comprises administering to said mammal a effective amount of a compound of formula (1), its pharmaceutically acceptable salts and / or derivatized forms. The following examples illustrate the preparation of the compounds of the formula (1): Preparation 1 2,2 '- (1,3-Phenylene) diethyl diacetate 2,2 '- (1,3-phenylene) diacetic acid (10.0 g, 51 mmol) was dissolved in ethanol (100 ml) and the solution was treated dropwise with catalytic acetyl chloride (2.5 ml) . The reaction mixture was stirred at reflux for 18 hours before being allowed to cool and concentrated under reduced pressure. The residue was taken up in ethyl acetate (100 ml) and washed with a solution of sodium bicarbonate (3 x 50 ml) and brine (3 x 50 ml). The organic phase was dried over magnesium sulfate and concentrated under reduced pressure. The residue was triturated with pentane to yield the title product, 11.8 g. 1HNMR (CDCl 3, 400MHz) d 1, 31 (6H, t), 3.65 (4H, s), 4.20 (4H, c), 7.24-7.36 (4H, m). LRMS: m / z ES + 251 [MH] + Preparation 2 [3- (2-Ethoxy-2-oxoethyl) phenyl] acetic acid A solution of the diester of preparation 1 (44.3 g, 177 mmol) and 2,2 '- (1,3-phenylene) diacetic acid (59.2 g, 308 mmol) in ethanol (24 ml) and dioxane ( 290 ml) was treated dropwise with 12 M hydrochloric acid (4.9 ml, 58.8 ml). mmol). The reaction mixture was stirred and refluxed for 18 hours before being allowed to cool and concentrated to a low volume. The reaction mixture was diluted with toluene (125 ml) and the resulting suspension was filtered. The filtrate was concentrated under reduced pressure and the residue was taken up in water and neutralized with sodium bicarbonate. The mixture was diluted with ethyl acetate (200 ml) and the organic layer was separated and washed with a solution of sodium bicarbonate (5 x 30 ml) and brine (50 ml). The combined aqueous extracts were acidified to pH 3 with 6 M hydrochloric acid and extracted with ether (3 x 30 ml). The organic extracts were combined, dried over magnesium sulfate and concentrated under reduced pressure. The residue was triturated with pentane to give the title compound as a colorless solid 10.8 9- 1 NMR (CD3OD, 400MHz) d 1.25 (3H, t), 3.60 (2H, m), 3.63 (2H, m), 4.15 (2H, c), 7.18-7 , 32 (4H, m) LRMS: m / z ES + 245 [MNa] + Preparation 3 [3- (2-Hydroxy-2-methyl-propyl) -phenyl] -acetic acid A solution of the acid from preparation 2 (6.85 g, 32 mmol) in diethyl ether (100 ml) was cooled to 0 ° C and treated with a 3 M solution of methylmagnesium bromide in ether (23.5 ml, 70.0 mmol). The mixture of The reaction was allowed to warm gradually to room temperature. After 2 hours, the reaction is quenched by the addition of a saturated aqueous solution of ammonium chloride (200 ml). The organic phase was separated and washed with brine (100 ml), dried over magnesium sulfate and concentrated under reduced pressure. Purification by column chromatography on silica gel eluting with pentane: dichloromethane (60:40 to 0: 100) gave the title compound as a colorless oil, 6.23 g. 1 H NMR (CDCl 3, 400MHz) d 1, 22 (6H, s), 2.75 (2H, s), 3.63 (2H, s), 7.12-7.30 (4H, m). LRMS: m / z ES + 209 [MH] + Preparation 4 Acid. { 3- [2- (2-chloroacetylamino) -2-methyl-propyl] -phenyl} -acetic 2-Chloroacetonitrile (8.8 mL, 140 mmol) was added to a solution of the alcohol of Preparation 3 (16.0 g, 70 mmol), in acetic acid (33 mL). The resulting solution was cooled to 0 ° C, treated with concentrated sulfuric acid (33 ml) and the reaction mixture allowed to warm gradually to room temperature. After 4 hours, the reaction mixture was poured on ice and basified with solid sodium carbonate. The solution was extracted with ethyl acetate (2 x 500 ml) and the combined organic extracts were dried over magnesium sulfate and concentrated under reduced pressure to give the product. of the title as a colorless solid, 19.0 g. 1 H NMR (CDCIs, 400MHz) d 1, 36 (6H, s), 3.02 (2H, s), 3.62 (2H, s) 3.95 (2H, s), 6.19 (1H, s) ), 7.06-7.31 (4H, m) LRMS: m / z ES "282, 284 [MH] 'Preparation 5 [3- (2-Amino-2-methyl propyl) phenyl] methyl acetate A solution of the amide of Preparation 4 (5.1 g, 18 mmol), thiourea (1.6 g, 21 mmol) and acetic acid (18 mL) in methanol (80 mL) was heated to reflux in an atmosphere of nitrogen for 16 hours. The reaction mixture was cooled and filtered. The filtrate was concentrated under reduced pressure and the residue was dissolved in methanol (150 ml). The solution was saturated with hydrogen chloride gas and then heated to reflux for 16 hours. The solvent was reduced in vacuo and the residue was partitioned between ethyl acetate (200 ml) and 5% aqueous sodium carbonate (200 ml). The combined organic extract was washed with saturated sodium chloride (100 ml), dried over sodium sulfate and reduced in vacuo. The residue was purified on a strong ion exchange resin, eluting with methanol and then with 2N ammonia in methanol to elute the product. The eluent was concentrated in vacuo to give the title compound as a yellow oil, 2.68 g. 1 H NMR (CDCl 3, 400MHz) d 1, 14 (6H, s), 2.68 (2H, s), 3.62 (2H, s), 3.69 (3H, s), 7.08-7, 16 (3H, m), 7.23-7.27 (1H, m). LRMS: m / z ES + 236 [MH] + Preparation fi 1 - [3,5-bis (Benzyloxy) phenyl] -2-bromoethanone To a stirred solution of 1- [3,5-bis (benzyloxy) phenyl] ethanone (5 g, 15.04 mmol) in tetrahydrofuran (60 ml) and methanol (35 ml) was added tetrabutylammonium tribromide (7.25). g, 15.04 mmol) in tetrahydrofuran (20 ml) at room temperature. The reaction mixture was stirred for 24 hours and the solvent was removed in vacuo. The residue was dissolved in ethyl acetate (100 ml) and washed with water (2 x 50 ml). The combined organic extracts were dried over magnesium sulfate and concentrated to yield the desired compound as a yellow oil in quantitative yield. 1 H NMR (400 MHz, CDCl 3) d 4.38 (2H, s), 5.05 (4H, s), 6.81 (1 H, s), 7.10-7.25 (2H, m), 7.30-7.42 (10H, m).

LRMS: m / z APCI + 413 [MH +]. Preparation 7. { 3- [2- (. {2- [3,5-bis (Benzyloxy) phenyl] -2-hydroxyethyl} amino) -2-methylpropyl] phenyl} methyl acetate A stirred solution of the compound of preparation 6 (4.7 g, 11.4 mmol), the compound of preparation 5 (2.53 g, 11.4 mmol) and N-ethyldiisopropylamine (2 mL, 11.4 mmol) ) in tetrahydrofuran (140 ml) was heated to reflux for 24 hours. The reaction mixture was cooled to room temperature, sodium borohydride (647 mg, 17.10 mmol) was added and the mixture was stirred for 5 hours at room temperature. The reaction was quenched by the addition of methanol (5 ml) and the solvent was evaporated in vacuo. The residual orange oil was partitioned between dichloromethane (60 ml) and a saturated sodium hydrogen carbonate solution (40 ml). The phases were separated and the aqueous phase was extracted with dichloromethane (3 x 40 ml). The organic extracts were combined and concentrated in vacuo. Purification by column chromatography on silica gel using dichloromethane and then dichloromethane. no: methanol: ammonia 0.88 (95: 5: 0.5) as eluent produced the desired product, 4.50 g (70%). 1 H NMR (400 MHz, CD 3 OD) d 1, 01 (6H, d), 2.61 (4H, m), 3.58 (2H, s), 3.62 (3H, 5 s), 4.61- 4.64 (1H, dd), 5.03 (4H, s), 6.54-6.55 (1H, t), 6.63-6.64 (2H, d), 7.00-7, 01 (1H, d), 7.08-7.10 (2H, d), 7.16-7.20 (1H, t), 7.25-7.28 (2H, m), 7.31- 7.34 (4H, t), 7.38-7.40 (4H, d). LRMS: m / z APCI + 554 [MH + j. Preparation 8 [methyl methyl 3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino] methyl-2-methylpropyl) phenyl-acetate A mixture of the compound of preparation 7 (4.50 g, 8.13 mmol), ammonium formate (3.59 g, 113.86 mmol) and palladium hydroxide on carbon (900 mg) in ethanol (80 ml) was heated to reflux for 24 hours. The reaction mixture was cooled to room temperature, filtered through Arbocel® and washed with methanol (3 x 20 ml). The filtrate was concentrated in vacuo to give an orange oil as the desired product, 2.64 g (87%). 1 H NMR (400 MHz, CD 3 OD) d 1, 06 (3 H, s), 1.07 (3 H, s), 2.67-287 (4 H, m), 3.62 (2 H, s), 3.66 (3H, s), 4.56-4.59 (1H, c), 6.18-6.19 (1H, t), 6.34 (2H, d), 7.03-7.23 (4H , m).

LRMS: m / z APCI + 374 [MH +]. Preparation 9 [3- (2- { [2- (3,5-Dihydroxyphenyl) -2-hydroxyethyl] amino] -2-methylpro-pyl) phenyl] acetic acid A solution of 1M lithium hydroxide (21.2 ml, 21.2 mmol) was added to a solution of the compound of preparation 8 (2.64 g, 7.07 mmol) in tetrahydrofuran (30 ml) and the mixture of reaction was stirred for 24 hours. A 1M solution of hydrochloric acid (21.2 mL, 21.2 mmol) was added and the solvent was removed in vacuo. The crude residue was azeotropically distilled with methanol and the product was subsequently used without further purification. 1 H NMR (400 MHz, DMSO-de) d 1.07 (6H, s), 2.74-2.87 (4H, m), 3.39 (2H, s), 4.63-4.61 ( 1H, d), 6.14-6.15 (1H, t), 6.24-6.25 (2H, d), 6.96-7.22 (4H, m). LRMS: m / z APCI + 357 [MH + J. Preparation 10 1- (3,5-Bis-benzyloxy-phenyl) -2-bromo-ethanol Trimethylboroxin (0.58 ml, 4.20 mmol) in toluene (15 ml) was added to (R) -2- (diphenylhydroxymethylpyrrolidine) (1.48 g, 5.80 mmol) and the reaction was stirred under an atmosphere of nitrogen for 15 minutes. The solution was concentrated to a volume of 5 ml by distillation at 1 atmosphere and more toluene (10 ml) was added. The distillation / redilution cycle was performed 3 times to produce an orange solution (volume of toluene 10 ml). This solution was added in one portion to a stirred solution of the compound of preparation 6 (5.00 g, 12.2 mmol) in tetrahydrofuran (72 ml) at -8 ° C under a nitrogen atmosphere. To this mixture was added a solution of borane-dimethyl sulfide complex (1.60 ml, 16.8 mmol) in tetrahydrofuran (16 ml) by a syringe pump for 90 minutes maintaining a temperature of -8 ° C. After the addition was complete, methanol (16 ml) was added via a syringe pump for 45 minutes maintaining a temperature of 0 ° C and the reaction allowed to warm to room temperature for 12 hours. The solvent was removed in vacuo to give a yellow oil and methanol (80 ml) was added and it was removed in vacuo. Methanol (80 ml) was added and removed in vacuo and the resulting yellow oil was dissolved in dichloromethane (500 ml), washed with 1 M aqueous hydrochloric acid (96 ml) and water (2 x 120 ml), dried ( magnesium sulfate) and the solvent was removed in vacuo to yield the title compound as a cream colored solid, 4.73 g. 1 H NMR (400MHz, CD3OD) d 3.52 (1H, m), 3.62 (1H, m), 4.82 (1H, dd), 5.09 (4H, s), 6.60 (1H, m), 6.69 (1H, s), 6.70 (1H, s), 7.33 (2H, m), 7.40 (4H, m), 7.45 (5H, m). LRMS: m / z electrospray 413, 415 [M + H +]. Preparation 11 [1- (3,5-Bis-benzyloxy-phenyl) -2-bromo-ethoxy] -tert-butyl-dimethyl-silane Tert-butyldimethylsilane silanotriflate (3.40 ml, 7.45 mmol) was added dropwise to a solution of the compound of preparation 10 (3.08 g, 7.45 mmol) and 2,6-lutidine (1, 75 ml, 15.0 mmol) in dichloromethane (74 ml) at 0 ° C, under a nitrogen atmosphere. The reaction was allowed to warm to room temperature for 12 hours and then washed with 1 M aqueous hydrochloric acid (2 x 24 ml), water (2 x 32 ml), dried (magnesium sulfate) and the solvent removed in vacuo. to give a yellow oil. This oil was purified by column chromatography on silica gel eluting with dichloromethane to give the title compound as a colorless oil, 3.51 g. 1 H NMR (400MHz, CD3OD) d 0.07 (3H, s), 0.13 (3H, s), 0.93 (9H, s), 3.52 (2H, m), 4.86 (1H, dd), 5.10 (4H, s), 6.60 (1H, m), 6.65 (1H, s), 6.66 (1H, s), 7.33 (2H, m), 7.40 (4H, m), 7.45 (4H, m). LRMS: m / z electrospray 549 [M + Na +].

Preparation 19 Methyl ester of 3- acid. { 2- [2- (3,5-bis-benzyloxy-phenyl) -2- (tert-butyl-dimethyl-silanyloxy) -ethylamino] -2-methyl-propyl} -benzoic A solution of the compound of Preparation 11 (2.54 g, 4.80 mmol) and the compound of Preparation 21 (2.00 g, 9.60 mmol) in dichloromethane (40 mL) was heated to 75 ° C. C and the solvent was allowed to evaporate. The resulting melt was heated at 75 ° C for 4 days and allowed to cool to room temperature. The residue was purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (100: 0: 0 then 95: 5: 0.5) to give the title compound as a yellow oil, 2, 00 g. 1 H NMR (400 MHz, CD 3 OD) d 0.18 (3 H, s), -0.04 (3 H, s), 0.78 (9 H, s), 1, 11 (3 H, s), 1, 13 (3 H , s), 2.70 (4H, m), 3.92 (3H, s), 4.70 (1H, dd), 5.12 (4H, s), 6.60 (1H, m), 6 , 62 (1H, s), 6.63 (1H, s), 7.32 (2H, m), 7.38 (6H, m), 7.45 (4H, m), 7.92 (2H, m). LRMS: m / z electronebulization 654 [M + H +].

Preparation 13 3- Methyl ester. { 2- [2- (tert-butyl-dimethyl-silanoxy) -2- (3,5-dihydroxy-phenyl) -ethylamino] -2-methyl-propyl) -benzoic acid Palladium hydroxide (340 mg) in one portion was added to a stirred solution of the compound of preparation 12 (1.97 g, 3.00 mmol) and ammonium formate (2.17 g, 47.1 mmol) in ethanol ( 31 ml) at room temperature. The reaction was refluxed for 2 hours and allowed to cool to room temperature. The reaction was filtered through Arbocel® and the filtrate was concentrated in vacuo to yield the title compound as a white foam, 1.41 g. 1 H NMR (400MHz, CD3OD) d -0.11 (3H, s), -0.00 (3H, s), 0.81 (9H, s), 1, 13 (3H, s), 1.15 (3H, s), 2.70 (4H, m), 3.96 (3H, s), 4.63 (1H, dd) , 6.22 (1H, m), 6.33 10 (1H, s), 6.34 (1H, s), 7.42 (2H, m), 7.92 (2H, m). LRMS: m / z electrospray 474 [M + H +], 496 [MNa +], 472 [M-K]. Preparation 14 Acid 3-. { 2- [2- (tert-Butyl-dimethyl-silanyloxy) -2- (3,5-dihydroxy-phenyl) -ethylamino) -2-methyl-propyl} -benzoic 1 M aqueous lithium hydroxide (9.00 ml, 9.00 mmol) in one portion was added to a stirred solution of the compound of preparation 13 (1.39 g, 2.93 mmol) in tetrahydrofuran (30 ml) at room temperature. The reaction was stirred at room temperature for 24 hours and 1 M aqueous hydrochloric acid (9.00 ml, 9.00 mmol) was added in one portion. The solvent was removed in vacuo to yield the title compound as a brown foam, 2.06 g. ? NMR (400MHz, CD3OD) d -0.05 (3H, s), 0.07 (3H, s), 0.83 (9H, s), 1.35 (3H, s), 1.37 (3H, s), 3.08 (2H, m), 3.25 (2H, m), 4.93 (1H, m), 6.29 (1H, m), 6.38 (1H, s), 6, 39 (1H, s), 7.42 (2H, m), 7.92 (1H, m), 8.00 (1H, m). LRMS: m / z electrospray 460 [M + H +]. Preparation 15 3-. { 2- [2- (tert-Butyl-dimethyl-silanyloxy) -2- (3,5-dihydroxy-phenyl) -ethylamino] -2-methyl-propyl} -? / - [2- (4-chloro-phenyl) -ethyl] -benzamide 4-Chlorphenethylamine (967 mg) was added, 6.20 mmol), triethylamine (1.00 ml, 7.20 mmol), hydroxybenzotriazole (567 mg, 4.20 mmol) and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (910 mg, 4, 74 mmol) was added to a stirred solution of the compound of Preparation 14 (2.06 g, 3.50 mmol) in N,? / - dimethylformamide (35 mL) at room temperature under a nitrogen atmosphere. The reaction was stirred for 12 hours and the solvent was removed in vacuo, then the residue was azeotropically distilled with toluene (20 ml) and purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (100: 0). : 0 then 95: 5: 0.5 and then 90: 10: 1) and was subjected to another column eluting with ethyl acetate: pentane: ammonia 880 (0: 100: 0 changing to 80: 20: 5 in 10% steps) to yield the title compound as a cream colored foam, 773 mg. 1 H NMR (400MHz, CD30D) d -0.10 (3H, s), 0.01 (3H, s), 0.84 (9H, s), 1.12 (3H, s), 1.14 (3H , s), 2.74 (4H, m), 3.94 (2H, m), 3.62 (2H, m), 4.66 (1H, dd), 6.22 (1H, m), 6 , 34 (1H, s), 6.35 (1H, s), 7.42 (6H, m), 7.67 (2H, m). LRMS: m / z electrospray 597 [M + H +] Preparation 16 1- (3-Bromophenyl) -2-methylpropan-2-ol) Methylmagnesium bromide (3 M solution in diethyl ether, 51.6 mL, 155 mmol) was added slowly to a solution of 1- (3-bromo-phenyl) propan-2-one (15.0 g, 70 mmol) in anhydrous diethyl ether (200 ml) at 0 ° C. The resulting mixture was allowed to stand for 3 hours, then cooled to 0 ° C and quenched slowly with a saturated aqueous solution of ammonium chloride. The organic phase was washed with brine and dried (sodium sulfate). Then, the yellow oil was purified by column chromatography on silica gel eluting with dichloromethane: pentane: methanol (90: 5: 5 by volume) to yield a pale yellow oil (13.26 g). 1 H NMR (400MHz, CDCl 3) d = 7.40 (2H, m), 7.15 (2H, m), 2.74. (2H, s), 1.42 (1H, s a), 1.22 (6H, s). Preparation 17? / - [2- (3-Bromophenyl) -1,1 -dimethylethyl] -2-chloroacetamide Chloroacetonitrile (6.63 ml, 105 mmol) was added to a stirred solution of 1- (3-bromophenyl) -2-methylpropan-2-ol) (Preparation 16) (12.0 g, 52.0 mmol) in acid acetic acid (25 ml) at room temperature. The resulting solution was cooled to 0 ° C and concentrated sulfuric acid (25 ml) was added maintaining the temperature < 10 ° C. The resulting solution was allowed to stir for 1 hour and then poured onto ice and basified by the addition of solid potassium carbonate. The product was extracted with ethyl acetate (2 x 500 ml), the organic extracts were combined and washed with water (50 ml), dried (sodium sulfate) and the solvent removed in vacuo to yield title compound in the form of an orange solid (16.08 g). 1 H NMR (400MHz, CDCl 3) d = 7.39-7.32 (1H, d), 7.26 (1H, s), 7.1-7.13 (1H, t), 7.08-7 , 03 (1H, d), 6.17 (1H, sa), 3.94 (2H, s), 3.02 (2H, s), 1.37 (6H, s). CHN for C? H 5BrCINO cale, (found): C 47.32 (47.26), H 4.96 (4.87), N 4.60 (4.65). LRMS (electrospray) m / z 306 [M + H] + Preparation 18 2- (3-Bromophenyl) -1,1-dimethylethylamine A solution of? / - [2- (3-bromophenyl) -1,1-dimethylethyl] -2-chloroacetamide (Preparation 17) (32.0 g, 105 mmol), thiourea (9.60 g, 126 mmol) and Acetic acid (50 ml) in ethanol (250 ml) was heated to reflux overnight. The reaction mixture was cooled to room temperature and filtered, the filtrate was concentrated in vacuo and basified using an aqueous solution of sodium hydroxide (1 M, 450 mL). The product was extracted with dichloromethane (2 x 500 ml) and the combined organic extracts were washed with brine (50 ml), dried (sodium sulfate) and the solvent removed in vacuo to yield the title compound as an oil. black (23 g). 1 H NMR (400MHz, CDCl 3) d = 7.36-7.32 (2H, m), 7.16-7.08 (2H, m), 2.62 (2H, s), 1.84 (2H, sa), 1.12 (6H, s). LRMS (electrospray) m / z 228 [M + H] + Preparation 19 [2- (3-Bromophenyl) -1,1 -dimethylethyl] carbamic acid tere-butyl ester 2- (3-Bromophenyl) -1,1-dimethylethylamine (Preparation 18) was treated (5.0 g, 22 mmol) with di-tert-butyl dicarbonate (5.26 g, 24 mmol) in dichloromethane (50 ml) and stirred for 20 hours. The reaction mixture was washed with water (50 ml), the combined organic extracts were dried (sodium sulfate) and the solvent was removed in vacuo. The crude material was purified using a cation exchange column (methanol followed by 2 M ammonia in methanol), followed by purification by flash column chromatography on silica gel eluting with dichloromethane to yield the title compound as a brown oil (7.23 g). 1 H NMR (400MHz, CDCl 3) d = 7.35 (1H, d), 7.30 (1H, s), 7.15-7.11 (1H, t), 7.05 10 (1H, d) , 4.24 (1H, sa), 2.97 (2H, s), 1.50 (9H, s), 1.27 (6H, s). LRMS (electrospray) m / z 350 [M + NH4] + Preparation 20 Methyl ester of 3- (2-tert-butoxycarbonylamino-2-methylpropyl) benzoic acid A solution of tere-butyl ester of [2- (3-bromophenyl) -1,1-dimethylethyl] carbamic acid (Preparation 19) (7.0 g, 21 mmol), [1,1'-bis (diphenylphosphine) ferrocene ] dichloropalladium (II) (1.74 g, 2.1 mmol) and triethylamine (5.94 mL, 43 mmol) in methanol (250 mL) was heated to 100 ° C under a pressure of 689.29 kPa (100 psi) ) of carbon monoxide for 12 hours. The reaction mixture was filtered through Arbocel® and the filtrate was concentrated in vacuo and purified by flash column chromatography on silica gel eluting with dichloromethane: pentane (50:50 by volume) to produce the title compound as a yellow solid (3.76 g). 1 H NMR (400MHz, CDCl 3) d = 7.92-7.90 (1H, m), 7.82 (1H, s), 7.35-7.34 (2H, m), 4.24 (1H , sa), 3.90 (3H, s), 3.05 (2H, s), 1.48 (9H, s), 1.26 (6H, s). LRMS (electrospray) m / z 208 [M + H-BOC] * Preparation 91 Ester methyl 3- (2-amino-2-methylpropyl) benzoic acid A solution of 3- (2-tert-butoxycarbonylamino-2-methylpropyl) benzoic acid methyl ester (Preparation 20) (1.6 g, 5.2 mmol) in dichloromethane (160 ml) at 0 ° C was treated with acid trifluoroacetic (13.6 ml) and allowed to warm to room temperature for 2 hours. The solvent was removed in vacuo and the product was purified by cation exchange chromatography (methanol followed by 2M ammonia in methanol) to yield the title compound as an amber oil (1.06 g). 1 H NMR (400MHz, CDCl 3) d = 7.90-7.88 (1H, m), 7.84 (1H, s), 7.36-7.35 (2H, m), 3.90 (3H, s), 2.71 (2H, s), 1.67 (2H, sa), 1.12 (6H, s). LRMS (electrospray) m / z 208 [M + H] + Preparation 92. { 3 - [(2R) -2-Aminopropyl] phenyl} methyl acetate A solution of [3 - ((2R) -2-. {[[(L R) -1-phenyl-ethyl] -amino} - propyl) -phenyl] -acetic acid methyl ester (Preparation 23) ( 7.69 g, 22 mmol) and ammonium formate (6.94 g, 110 mmol) was heated to 75 ° C in the presence of 20% palladium hydroxide on carbon (Pd (OH) 2 / C, 2.00 g. ). After 90 minutes, the reaction mixture was cooled to room temperature, filtered through Arbocel® and the filtrate was concentrated in vacuo. The residue was partitioned between dichloromethane (100 ml) and 880 ammonia (100 ml) and the organic phase was separated. The aqueous phase was extracted with dichloromethane (100 ml) and the combined organic extracts were dried (magnesium sulfate) and reduced in vacuo to give the title compound as a colorless oil (4.78 g). 1 H NMR (400MHz, CD3OD): d = 7.27-7.23 (1H, t), 7.13-7.09 (3H, m), 3.67 (3H, s), 3.63 (2H , s), 3.12-3.05 (1H, m), 2.67-2.57 (2H, m), 1, 06 (3H, d) ppm. LRMS (electrospray): m / z [M + H] + 208, [M + Naf 230.

Preparation of [3 - ((2R) -2-. {[[(1 R) -1-phenyl-ethyl] -amino} -propyl) -phenyl] -acetic acid methyl ester A solution of methyl [3- (2-oxopropyl) phenyl] acetate (Preparation 24) (8.50 g, 41.2 mmol), (R) -a-methylbenzylamine (4.8 mL, 37.2 mmol) Sodium triacetoxyborohydride (11.6 g, 56 mmol) and acetic acid (2.2 ml, 38 mmol) in dichloromethane (400 ml) was stirred at room temperature for 48 hours. The reaction mixture was quenched by the addition of saturated aqueous sodium bicarbonate (200 ml) and allowed to stir until effervescence ceased. The organic phase was separated and the aqueous phase was extracted with dichloromethane (100 ml). The combined organic extracts were dried (magnesium sulfate) and reduced in vacuo. Purification by flash column chromatography eluting with dichloromethane: methanol: ammonia (99: 1: 0.1 to 95: 5: 0.5 by volume) gave a 4: 1 mixture of diastereomers (mainly R, R) in the form of a pale yellow oil (8.71 g). Treatment with hydrogen chloride (40 ml of a 1M solution in methanol, 40 mmol) followed by three successive crystallizations (diisopropyl ether / methanol) gave the title compound as a white crystalline solid (5.68 g). 1 H NMR (400MHz, CD3OD): d = 7.52-7.48 (5H, m), 7.28-7.25 (1H, m), 7.18-7.16 (1H, m), 7.02-6.99 (2H, m), 4.59 (1H, c), 3.62 (2H, s), 3.30 (3H, s), 3.30-3.25 (1 H, m), 3.26-3.15 (1H, m), 2.66-2.60 (1H, m), 1.68 ( 3H, d), 1, 18, (3H, d) ppm. LRMS (electrospray): m / z [M + H] + 312, [M + Na] + 334. Preparation 94 [3- (2-Oxopropyl) phenyl] methyl acetate Tributyltin methoxide (28.3 ml, 98 mmol), the compound of preparation 25 (15.0 g, 65 mmol), isopropenyl acetate (10.8 ml, 98 mmol), palladium (II) acetate were stirred. (750 mg, 3.30 mmol) and tri-ortho-tolylphosphine (2.0 g, 6.5 mmol) in toluene (75 ml) at 100 ° C under a nitrogen atmosphere for 5 hours. After cooling, the reaction was diluted with ethyl acetate (150 ml) and a 4 M aqueous potassium fluoride solution (90 ml) and stirred for 15 minutes. The mixture was filtered through arbocel and the organic phase was separated and reduced in vacuo. The residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of diethyl ether.-pentane (0: 100 to 25:75, in volume) changing to dichloromethane to give the title compound as a pale yellow oil (12.6 g). 1 H NMR (400MHz, CDCl 3): d = 7.30 (1H, t), 7.19 (1H, d), 7.13-7A0 (2H, m), 3.69 (5H, s), 3, 61 (2H, s), 2.15 (3H, s) ppm. LRMS (electrospray): m / z [M + NH4f 224, [M + Na] + 229.

Preparation 95 (3-Bromophenyl) methyl acetate Acetyl chloride (0.7 ml, 9.3 mmol) was added slowly to a solution of (3-bromophenyl) -acetic acid (20.0 g, 93 mmol) in methanol (500 ml) at 0 ° C in a nitrogen atmosphere and the reaction was allowed to warm gradually to room temperature over a period of 5 hours. The solvent was removed in vacuo and the residual oil redissolved in dichloromethane, dried (sodium sulfate) and concentrated in vacuo to give the title compound as a colorless oil (20.6 g). 1 H NMR (400MHz, CDCl 3): d = 7.37-7.45 (2H, m), 7.24-7.17 (2H, m), 3.70 (3H, s), 3.59 (2H , s) ppm. LRMS (electrospray): m / z [M + Na] + 253. Preparation 26 Acid [3 - ((2R) -2- { [(1 R) -1-phenyl-etiI] -amino.} - propyl) -phenyl] -acetic 1 M aqueous lithium hydroxide (90 ml, 90 mmol) was added in one portion to a stirred solution of the compound of preparation 23 (13.5 g, 43.5 mmol) in methanol (2000 ml) at room temperature. The reaction was stirred at room temperature for 24 hours and added in one portion 1 M aqueous hydrochloric acid (90 ml, 90 mmol). The solvent was removed in vacuo to reduce the volume to 80 ml and the white precipitate was removed by filtration and washed with water (20 ml) and 20% ethanol (100 ml) and dried to yield the title compound in the form of a white solid, 11, 8 g. 1 H NMR (400MHz, CD3OD) d 1.16 (3H, d), 1.62 (3H, d), 2.64 (1H, m), 3.20 (2H, m), 3.46 (2H, s), 4.42 (1H, c), 6.91 (1H, d), 7.08 (1H, s) , 7.19 (1H, s), 7.20 (1H, m), 7.48 (5H, m). LRMS: m / z electrospray 298 [M + H +], 296 [M-H ^. Preparation 27? / - Adamantan-1-yl-2-. { 3- [2- (1-phenyl-ethylamino) -propyl] -phenyl} -aceta- To a stirred suspension of the compound of Preparation 26 (297 mg, 1.00 mmol) in dichloromethane (4 mL) at room temperature was added 1-adamantylamine (151 mg, 1.00 mmol) and the suspension was stirred for 15 minutes. minutes 2-Chloro-1,3-dimethylimidazolinium hexafluorophosphate (278 mg, 1.00 mmol) was added in one portion and the reaction was stirred for 2 hours, after which the reaction was homogeneous. The reaction was washed with water (5 ml), dried (magnesium sulfate) and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (98: 2: 0.2 then 95: 5: 0.5) to afford the title compound as a pale yellow foam, 325 mg. 1 H NMR (400MHz, CD3OD) d 0.89 (3H, d), 1, 36 (3H, d), 1.75 (6H, m), 1.98 (6H, s), 2.04 (6H, s), 2.40 (1 H, dd), 274 (1 H, m), 3.00 (1 H, dd), 3.36 (2 H, s), 4.00 (1 H, c), 6 , 90 (1H, d), 6.98 (1H, s), 7.08 (1H, d), 7.19 (1H, t), 7.22 (1H, m), 7.38 ( 4H, m). LRMS: m / z electrospray 431 [M + H +]. Preparation 98? / - Adamantan-1-yl-2- [3- (2-amino-propyl) -phenyl] -acetamide A solution of the compound of preparation 27 (17.6 g, 36 mmol) and ammonium formate (22.7 g, 360 mmol) was heated to 70 ° C in the presence of 20% palladium hydroxide on carbon (Pd (OH 2 / C, 2.00g). After 60 minutes more catalyst (500 mg) was added and the reaction was heated for a further 4 hours. The reaction mixture was cooled to room temperature, filtered through Arbocel® and the filtrate was concentrated in vacuo. The residue was partitioned between dichloromethane (300 ml) and 10% 880 ammonia in water (150 ml) and the organic phase was separated, dried (sodium sulfate) and reduced in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (95: 5: 0.5 and then 90: 10: 1) to produce the title compound as a white solid, 10.8 g. 1 H NMR (400MHz, CD 3 OD): d 1, 09 (3H, d), 1.68 (6H, m), 2.00 (6H, s), 2.03 (3H, s), 2.64 (2H , m), 3.14 (1H, c), 3.40 (2H, s), 7.14 (4H, m). LRMS (electrospray): m / z [M + H] + 327. Preparation 29? / - Adamantan-1-yl-2- (3- { 2- [2- (3,5-bis-benzyloxy-phenyl) ) -2- (tert-Butyl-dimethyl-silanyloxy) -ethylamino] -propyl.} - phenyl) -acetamide A solution of the compound of preparation 11 (263 mg, 0.50 mmol) and the compound of Preparation 28 (326 mg, 1.00 mmol) in dichloromethane (1 mL) was heated to 90 ° C and the solvent allowed to evaporate. The resulting melt was heated at 90 ° C for 1 day and then allowed to cool to room temperature. The residue was purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (98: 2: 0.2) to yield the title compound as a clear oil, 168 mg. 1 H NMR (400MHz, CD3OD) d -0.09 (3H, s), -0.02 (3H, s), 0.82 (9H, s), 1.03 (3H, d), 1.66 ( 6H, s), 1, 99 (6H, s), 2.02 (3H, s), 2.59 (1H, m), 2.65 (2H, m), 2.85 (2H, m), 3.37 (2H, s), 4.86 (1H, m), 5.06 (4H, m), 6.54 (3H, m) , 7.00 (14H,). LRMS: m / z electrospray 773 [M + H +]. Preparation 3? / - Adamantan-1-yl-2- (3- { 2- [2- (tert-butyl-dimethyl-silanyloxy) -2- (3,5-dihydroxy-phenyl) -ethylamino] -propyl .}.-phenyl) -acetamide A solution of the compound of preparation 29 (160 mg, 0.21 mmol) and ammonium formate (150 mg, 2.10 mmol) was heated to 70 ° C in the presence of 20% palladium hydroxide on carbon (Pd (OH 2 / C, 20 mg). After 3 hours, the reaction mixture was cooled to room temperature, filtered through Arbocel® and the filtrate was concentrated in vacuo. The residue was partitioned between ethyl acetate (10 ml) and 10% 880 ammonia in water (10 ml) and the organic phase was separated and dried. The aqueous layer was extracted with dichloromethane (2 x 50 ml) and the combined organic extracts were dried (sodium sulfate) and reduced in vacuo to yield the title compound as a yellow foam, 160 mg. 1 H NMR (400MHz, CD 3 OD) d -0.16 (3H, s), 0.01 (3H, s), 0.84 (9H, s), 1.03 (3H, d), 1.69 (6H , m), 2.01 (9H, m), 2.60 (3H, m), 2.91 (2H, m), 3.39 (2H, s), 4.60 (1H, m), 6.13 (1H, m), 6.20 (2H, m), 6.98 (1H, d), 7.05 (1H , s), 7.07 (1H, d), 7.18 (1H, t). LRMS: m / z electrospray 593 [M + H +], 591 [MH] "Preparation 31 (3 { 2- [2- (3,5-bis-benzyloxy-phenyl) -2- methyl ester. (tert-butyl-dimethyl-silanyloxy) -ethylamino] -2-methyl-propyl.} - phenyl) -acetic A solution of the compound of preparation 11 (5.30 g, 10.0 mmol) and the compound of preparation 5 (4.42 g, 20.0 mmol) was combined and heated to 92 ° C under an atmosphere of nitrogen. The resulting melt was heated at 92 ° C for 24 hours and then allowed to cool to room temperature. The residue was purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (98: 2: 0.2) to give the title compound as a golden oil, 5.38 g. 1 H NMR (400MHz, CD 3 OD) d -0.20 (3H, s), -0.03 (3H, s), 0.79 (9H, s), 1.01-1, 03 (6H, d), 2.58-2.82 (4H, m), 3.59 (2H, s), 3.63 (3H, s), 4.62-4.66 (1H, m), 4.84 (4H , s), 6.76 (3H, s), 7.15-7.65 (14H, m). LRMS: m / z electrospray 668 [M + H +].

Preparation 32 Acid (3- { 2- [2- (3,5-bis-benzyloxy-phenyl) -2- (tert-butyl-dimethylsilanyl-xi) -ethylamino] -2-methyl-propyl.} .-phenyl) -acetic 1M aqueous lithium hydroxide (8.80 ml, 8.80 mmol) was added in one portion to a stirred solution of the compound of preparation 31 (5.30 g, 7.95 mmol) in tetrahydrofuran (150 ml) at room temperature in a nitrogen atmosphere. The reaction was stirred at room temperature for 24 hours and 1 M aqueous hydrochloric acid (8.80 mL, 8.80 mmol) was added in one portion. The majority of the solvent was removed in vacuo and the resulting mixture was partitioned between dichloromethane (200 ml) and water (200 ml). The organic layer was washed with brine (50 ml), dried (sodium sulfate) and the solvent removed in vacuo to give the title compound as a colorless foam (5.16 g). 1 H NMR (400MHz, CD 3 OD) d -0.17 (3H, s), 0.02 (3H, s), 0.82 (9H, s), 1.26 (6H, s), 2.84-2 , 96 (2H, c), 3.18-3.19 (2H, d), 3.53 (2H, s), 4.87-4.92 (1H, t), 5.10 (4H, s ), 6.60-6.63 (3H, m), 7.03-7.43 (14H, m) LRMS: m / z electrospray 654 [M + H +].

Preparation 33 Acid (3- { 2- [2- (tert-butyl-dimethylsilanyloxy) -2- (3,5-dihydroxy-phenyl) -ethylamino] -2-methyl-propyl.} - phenyl) -acetic Palladium hydroxide (500 mg) was added in one portion to a stirred solution of the compound of preparation 32 (5.10 g, 7.81 mmol) and 0-ammonium formate (5.00 g, 74.6 mmol) in ethanol (250 ml) at room temperature. The reaction was heated at 70 ° C for 3 hours. Then more palladium hydroxide (250 mg) was added and the reaction was heated at 70 ° C for a further 1.5 hours and allowed to cool to room temperature under a nitrogen atmosphere overnight. The reaction was filtered through Arbocel® and the filtrate was concentrated in vacuo. The residue was triturated with water (50 ml) and filtered to yield the title compound as a white solid, 3.61 g. 1 H NMR (400MHz, CD3OD) d -0.07 (3H, s), 0.03 (3H, s), 0.83 (9H, s), 1.34 (6H, s), 2.90-2 , 97 (2H, c), 3.18-3.19 (2H, s), 3.50-3.58 (2H, c), 4.85-4.95 (1H, m), 6.12 (1H, s), 6.35 (2H, s), 7.03-7.35 (4H, m). or LRMS: m / z electrospray 474 [M + H +].

Preparation 34 2- (3-. {2- [2- (tert-Butyl-dimethyl-silanyloxy) -2- (3,5-dihydroxy-phenyl) -ethylamino] -2-methyl-propyl} -phenyl ) - / - (3,4-dichloro-benzyl) -acetamide 3,4-Dichlorobenzylamine (53 mg, 0.301 mmol), hydroxybenzotriazole (39 mg, 0.289 mmol) and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (57 mg, 0.297 mmol) were added to a stirred solution of the compound of Preparation 33 (142 mg, 0.300 mmol) in N,? / - dimethylformamide (2 mL) at room temperature under a nitrogen atmosphere. The reaction was stirred for 18 hours and the solvent was removed in vacuo and then the residue was partitioned between dichloromethane (50 ml) and saturated aqueous sodium hydrogen carbonate (50 ml). The organic layer was dried (sodium sulfate) and the solvent was removed in vacuo and purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (95: 5: 0.5) to give the title compound in the form of a cream colored foam, 125 mg. 1 H NMR (400MHz, CD 3 OD) d -0.16 (3H, s), 0.00 (3H, s), 0.82 (9H, s), 1.01-1, 03 (6H, d), 2 , 60-2.86 (4H, m), 3.52 (2H, s), 4.31 (2H, s), 4.78-4.81 (1H, m), 6.18 (1H, s) ), 6.29 (2H, s), 7.02-7.24 (5H, m), 7.36-7.42 (2H, m). LRMS: m / z electronebulization 631 [M + H +].

Preparation 35 (3- {2- [2- (3,5-bis-benzyloxy-phenyl) -2- (tert-butyl-dimethyl-silanyloxy) -ethylamino] -propyl} -phenyl acid methyl ester )-acetic A solution of the compound of preparation 11 (5.00 g, 9.45 mmol) and the compound of preparation 22 (3.92 g, 18.9 mmol) in dichloromethane (50 ml) was heated to 95 ° C. C and the solvent was removed by evaporation. The resulting melt was heated at 95 ° C for 24 hours and then allowed to cool to room temperature. Diethyl ether (50 ml) was added and the mixture was stirred for 5 minutes. The ether layer was separated from the gum and then the gum was extracted twice more with diethyl ether (2 x 50 ml). The ether extracts were combined and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (100: 0: 0 to 95: 5: 0.5) to afford the title compound as a pale yellow gum 4.50 g. 1 H NMR (400MHz, CD 3 OD) d -0.20 (3H, s), -0.05 (3H, s), 0.81 (9H, s), 1.01-1, 03 (3H, d), 2.60 (3H, m), 2.86 (2H, m), 3.55 (2H, s), -3.63 (3H, s), 4.66 (1H, m), 4.85 (4H, m), 6.70 (3H, m), 6.73 (1H, m), 6.98 (2H, m), 7.06 (1H, m), 7.17 (1H, m) , 7.10 (2H, m), 7.11-7.22 (7H, m).

LRMS: m / z electronebulization 654 [M + H +]. Preparation 3fi 3-. { 2- [2- (tert-Butyl-dimethyl-silanyloxy) -2- (3,5-dihydroxy-phenyl) -ethylamino] -2-methyl-propyl} -? / - [2- (3-Fluoro-phenyl) -ethyl] -benzamide 2-Fluorophenylethylamine (95 mg, 0.680 mmol), hydroxybenzotriazole (100 mg, 0.740 mmol), triethylamine (0.10 mL, 0.720 mmol) and 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (79 mg, 0.410 mmol) was added to a stirred solution of the compound of preparation 14 (151 mg, 0.330 mmol) in? /, / V-dimethylformamide (1 mL) at room temperature under a nitrogen atmosphere. The reaction was stirred for 18 hours and the solvent was removed in vacuo and purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (100: 0: 0 to 95: 5: 0.5 to 90: 10: 1) to produce the title compound in the form of a cream-colored foam, 132 mg. 1 H NMR (400MHz, CD 3 OD) d -0.16 (3H, s), -0.02 (3H, s), 0.78 (9H, s), 1.12 (6H, d), 2.65- 2.95 (6H, m), 3.61 (2H, s), 4.64 (1H, s), 6.18 (1H, s), 6.29 (2H, s), 6.93 ( 1H, m), 7.02 (1 H, m), 7.06 (IH, m), 7.20-7.39 (3H, m), 7.64 (2H, m).

LRMS: m / z electrospray 581 [M + H +]. Preparations 37 to 43 were prepared from compound 14 and the appropriate amine using the method described for 36: Preparations 37 to 43 Q1 Data The compound was isolated in the form of a brown oil 1H-NMR (400MHz, CD3OD) d -0.16 (3H, s), -0.02 (3H, s), 0.78 (9H, s), 1.08 (6H, d), 2.60-2.84 (4H, m), 3.08 (2H, m), 3.64 (2H, m), 4.61 (1H, m), 6.18 (1H, s), 6.29 (2H, s), 7.13-7.39 (6H, m), 7.63 (2H, m ). LRMS: m / z electrospray 597 [M + H +]. The compound was isolated as a white foam.1H-NMR (400MHz, CD3OD) d -0.16 (3H, S), 0.02 (3H, s), 0.80 (9H, s), 1, 08 (6H, d), 2.27 (3H, s), 2.29 (3H, s), 2.60-2.89 (4H, m), 2.96 (2H, m), 3.55 (2H, m), 4.61 (1H, m), 6.18 (1H, s), 6.29 (2H, s), 6.93-7.03 (3H, m), 7.30-7.38 (2H, m), 7.65 (2H, m). LRMS: m / z electrospray 591 [M + H +]. fifteen twenty fifteen twenty Preparation 44 Acid (3-. {2- (2- (3,5-bis-benzyloxy-phenyl) -2- (tert-butyl-dimethyl-silane-loxi) -ethylamino] -propyl.} - phenyl) -acetic 1 M aqueous lithium hydroxide (16.0 ml, 16.0 mmol) was added in one portion to a stirred solution of the compound of preparation 35 (4.75 g, 7.26 mmol) in tetrahydrofuran (20 ml) at room temperature. The reaction was stirred at room temperature for 24 hours and 1 M aqueous hydrochloric acid was added until the pH reached a value of 1-2. Extraction was carried out with dichloromethane (1 x 200 ml and then 2 x 50 ml) and the combined organic layers were washed with brine (20 ml), dried (magnesium sulfate) and the solvent was removed in vacuo to yield the salt hydrochloride of the title compound in the form of a whitish foam, 4.80 g. 1 H NMR (400MHz, CD 3 OD) d -0.12 (3H, s), 0.06 (3H, s), 0.86 (9H, s), 1, 23 (3H, d), 2.77 (1H , m), 3.03 (1H, m), 3.23 (1H, m), 3.45-3.60 (3H, m), 5.01 (1H, m), 5.10 (4H, s), 6.64 (2H, m), 6.68 (1H, m), 7.10 (1H, m), 7.15 (1H, s), 7.23 (1H, m), 7.27-7.43 (11 H, m). LRMS: m / z APCl 640 [M H +].

Preparation 45 Acid (3- { 2- [2- (tert-butyl-dimethylsilanyloxy) -2- (3,5-dihydroxy-phenyl) -ethylamino] -propyl.} - phenyl) -acetic Palladium hydroxide (350 mg) was added in one portion to a stirred solution of the compound of preparation 44 (3.50 g, 5.48 mmol) and ammonium formate (1.80 g, 39.1 mmol) in ethanol ( 250 ml) at room temperature. The reaction was heated to reflux for 45 minutes and allowed to cool to room temperature. The reaction was filtered through Arbocel® and the filtrate was concentrated in vacuo to yield the title compound as a pale yellow solid, 2.30 g. 1 H NMR (400MHz, CD3OD) d -0.06 (3H, s), 0.06 (3H, s), 0.86 (9H, s), 1, 25 (3H, d), 2.81 (1H, m), 2.96 (1H, m), 3.15 (1H, m), 3.25 (1H, m) , 3.43-3.55 (3H, m), 4.89 (1H, m), 6.24 (1H, m), 6.33 (2H, m), 7.06 (1H, m), 7.17 (1H, s), 7.19-7.28 (2H, m). LRMS: m / z APCl 460 [M + H +]. Preparations 46 to 48, 55 to 65 and 73 to 76 were prepared from preparation 33 and the appropriate amine, using the method of preparation 34. These compounds have the generic formula and they are presented in the table shown below. Preparations 49 to 54, 66 to 72 and 77 to 87 were prepared from preparation 45 and the appropriate amine, using the method of preparation 34. These compounds have the generic formula and they are presented in the table shown below. 15 20 15 20 a (3H, s), m), 2.58, 4.57 (1H, (2H, m), [M-H *]. one (3H, s), m), 2.58, 4.58 (3H, (2H, m), fifteen [M-H *]. a (3H, s), d), 2.55 3.53 (2H, (1H, m), m), 7.06 [M-H "]. a solid (3H, s), s), 1.12 3.59 (2H, (1H, m), s), 7.25 d).

[M + H *], a solid (3H, s), s), 1.11 (2H, s), s), 7.10 7.27 (3H, [M + H *], a d • ß), 1.06 2.83 (1H, (1H, m), d), 7.11 m). [M + H *]. 15 20 a (3H, S), s), 1.08 (2H, s), s), 7.14 [M + H *]. one (3H, s), s), 1.08 2.83 (1H, (1H, s), m), 7.20 [M + H *]. a (3H, s), s), 1.04 2.83 (1H, (1H, m), d), 7.20, 7.48 (1H, [M + H *]. 15 20 15 20 15 20 Preparation 8 ». { 3 - [(2R) -2-Aminopropyl] phenyl} methyl acetate A solution of [3 - ((2R) -2- { [(1R) -1-phenyl-ethyl] -amino}.,. Propyl) -phenyl] -acetic acid methyl ester (Preparation 89) (13.65 g, 40.9 mmol) and ammonium formate (12.9 g, 204 mmol) in ethanol (200 ml) was heated to reflux in the presence of 20% palladium hydroxide on carbon (Pd (OH) 2 / C, 1 , 36 g). After 3 hours the reaction mixture was cooled to room temperature, filtered through arbocel and the filtrate was concentrated in vacuo. The residue was partitioned between dichloromethane (200 ml) and 880 ammonia (100 ml) and the organic phase was separated. The aqueous phase was extracted with more dichloromethane (3 x 100 ml) and the combined organic extracts were washed with brine (100 ml)., dried (sodium sulfate) and reduced in vacuo to give the title compound (8.48 g) as a pale yellow oil. 1 H NMR (400MHz, CDCl 3): d = 7.90-7.87 (2H, m), 7.38-7.34 (2H, m), 3.90 (3H, s), 3.26-3 , 17 (1H, m), 2.78-2.73 (1 H, dd), 2.64-2.59 (1H, dd), 1, 14-1, 12 (3H, d) ppm. LRMS (electrospray): m / z [M + H] + 194.

Preparation fifl [3 - ((2R) -2-. {[[(1-fi) -1-phenyl-ethyl] -amino} -propyl) -phenyl] -acetic acid hydrochloride A solution of methyl [3- (2-oxopropyl) phenyl] acetate (Preparation 90) (45.3 g, 236 mmol), (R) -a-methyl benzylamine (27.6 mL, 214 mmol), sodium triacetoxyborohydride (68.1 g, 321 mmol) and acetic acid (14.7 ml, 257 mmol) in dichloromethane (1500 ml) was stirred at room temperature for 18 hours. The reaction mixture was quenched by the addition of saturated aqueous sodium bicarbonate (600 ml) and allowed to stir until effervescence ceased. The organic phase was separated and the aqueous phase was extracted with more dichloromethane (2 x 100 ml). The combined organic extracts were washed with brine (100 ml), dried (sodium sulfate), filtered through celite and reduced in vacuo. The oil was dissolved in methanol (200 ml), treated with 1 M hydrogen chloride in methanol (300 ml) and reduced in vacuo to give a 4: 1 mixture of diastereomers (mainly R, R) in the form of a hydrochloride salt. whitish Two successive crystallizations gave the title compound (27.3 g) as an uncolored crystalline solid. 1 H NMR (400MHz, CD3OD): d = 7.92-7.90 (1H, d), 7.75 (1H, s), 7.55-7.49 (5H, m), 7.45-7 , 42 (1H, dd), 7.35-7.33 (1H, d), 4.68-4.63 (1H, c), 3.90 (3H, s), 3.43-3.38 (1H, dd), 3.25-3.19 (1H, m), 2.71-2.65 (1H, dd), 1, 71-1.69 (3H, d), 1, 17-1, 16, (3H, d) ppm. Preparation 90 [methyl 3- (2-oxopropyl) phenyl] acetate Tributyltin methoxide (80.3 ml, 279 mmol), methyl 3-bromobenzoate (53.5 g, 249 mmol), isopropenyl acetate (39.4 ml, 358 mmol), palladium acetate (II) (2.6 g, 11.6 mmol) and tri-o-tolylphosphine (7.1 g, 23.2 mmol) in toluene (350 mL) at 100 ° C in a Nitrogen atmosphere for 18 hours. After cooling, the reaction was treated with an aqueous 4 M potassium fluoride solution (560 ml) and stirred for 2 hours. The resulting mixture was diluted with more toluene (200 ml) and filtered through celite by washing the filter with ethyl acetate. The organic phase was separated, dried (sodium sulfate) and reduced in vacuo. The residue was purified by flash column chromatography on silica gel eluting with ethyl acetate: pentane (10:90, changing to 20:80, by volume) to give the title compound (45.3 g) as a orange oil 1 H NMR (400MHz, CDCl 3): d = 7.95-7.93 (1H, d), 7.87 (1H, s), 7.43-7.37 (2H, m), 3.91 (3H , s), 3.75 (2H, s), 2.18 (3H, s) ppm. LRMS (electrospray): m / z [M + Naf 215, [M-H] "191.

Preparation 91 3- Methyl ester. { 2- [2- (3,5-bis-benzyloxy-phenyl) -2- (tert-butyl-dimethyl-silanyloxy) -ethylamino] -propl} -benzoic The compound of preparation 11 (7.10 g, 13.5 mmol) was added to a solution of the compound of preparation 88 (5.23 g, 27.0 mmol) in dichloromethane (50 ml) and the solvent was removed to the vacuum The mixture was heated to 95CC for 12 hours and cooled to room temperature. Diethyl ether (150 ml) was added and the reaction was stirred for 1 hour, the resulting white precipitate was removed by filtration and the filtrate was evaporated to yield a yellow oil. The residue was purified by column chromatography on silica gel eluting with dichloromethane: methanor.amoniaco 880 (100: 0: 0 then 95: 5: 0.5) to afford the title compound as a yellow oil, 4, 30 g. 1 H NMR (400MHz, CD 3 OD) d -0.23 (3H, s), -0.06 (3H, s), 0.78 (9H, s), 1, 06 (3H, d), 2.57 ( 1H, m), 2.66 (2H, m), 2.88 (2H, m), 3.83 (3H, s), 4.64 (1H, m), 4.85 (4H, s), 6.46 (2H, s), 6.49 (1H, m), 7.32 (12H, m), 7.78 (1H, s), 7.82 (1H, m).

LRMS: m / z APCl 640 [M + H +]. Preparation 99 3- Hydrochloride. { 2- [2- (3,5-bis-benzyloxy-phenyl) -2- (tert-butyl-dimethyl-silanyloxy) -ethylamino] -propyl} -benzoic The compound of preparation 91 (5.35 g, 8.37 mmol) was stirred in tetrahydrofuran (20 ml) and 1 M aqueous lithium hydroxide (18.4 ml, 18.4 mmol) was added in one portion. The reaction was stirred for 12 hours and then heated at 40 ° C for 12 hours. Additional 1M aqueous lithium hydroxide was added (36, 8 mL, 36.8 mmol) and tetrahydrofuran (100 mL) in one portion and the reaction was heated at 40 ° C for 12 hours, the reaction was cooled and more 1 M aqueous lithium hydroxide (36.8 mL) was added. 36.8 mmol). The reaction was heated at 60 ° C for 5 hours and cooled to room temperature, the tetrahydrofuran was removed under reduced pressure and dioxane (50 ml) was added. The reaction was heated at 60 ° C for 1 hour, cooled to room temperature and the solvent removed in vacuo. The residue was acidified to pH 1 with 1 M aqueous hydrochloric acid and extracted with dichloromethane: methanol (97: 3; v / v; 3 x 150 ml), the combined organic extracts were washed with brine (30 ml), dried (magnesium sulfate) and the solvent was removed under vacuum produce the title compound in the form of a yellow foam, 5.00 g. 1 H NMR (400MHz, CD 3 OD) d -0.13 (3H, s), 0.07 (3H, s), 0.86 (9H, s), 1, 24 (3H, d), 2.83 (1H , m), 3.19 (1H, m), 3.30 (2H, m), 3.59 (1H, m), 5.05 (1H, m), 5.11 (4H, s), 6 , 64 (3H, m), 7.30 (10H, m), 7.47 (2H, m), 7.92 (1H, s), 7.97 (1H, m). LRMS: m / z APCl 626 [M + H +]. Preparation 93 Acid 3-. { 2- [2- (tert-butyl-dimethyl-silanyloxy) -2- (3,5-dihydroxy-phenyl) -ethylamino] -propyl} -benzoic The compound of preparation 92 (4.97 g, 7.95 mmol) was dissolved in ethanol (300 mL) and ammonium formate (2.75 g, 60 mmol) and palladium dioxide (500 mg) were added in one portion. . The reaction was refluxed for 1 hour, cooled to room temture, filtered through Arbocel® and washed with methanol (500 ml). The filtrate was condensed in vacuo to yield the title compound as an off-white solid, 3.60 g. 1 H NMR (400MHz, CD3OD) d -0.06 (3H, s), 0.05 (3H, s), 0.86 (9H, s), 1, 23 (3H, d), 2.83 (1H, m), 3.12 (2H, m), 3.25 (1H, m), 3.51 (1H, m) , 4.90 (1H, m), 6.24 10 (1H, m), 6.35 (2H, s), 7.27 (2H, m), 7.83 (1H, m), 7.88 (1 H, m). LRMS: m / z APCl 446 [M + H +]. Preparations 100 to 104 and 115 to 124 were prepared from preparation 33 and the appropriate amine, using the method of preparation 34. These compounds have the general formula and they are presented in the table shown below. Preparations 96 to 99 were prepared from preparation 45 and the appropriate amine using the method of preparation 34. These compounds have the general formula and they are presented in the table shown below. Preparations 94, 95 and 105 to 114 were prepared from preparation 93 and the appropriate amine using the method of preparation 34. These compounds have the general formula and they are presented in the table shown below. 15 20 The compound was isolated in the form of a pale brown foam. 1 H NMR (400MHz, CD 3 OD) d -0.15 (3H, s), -0.01 (3H, s), 0.82 (9H, s), 1.05 (3H, d), 2.32 ( 3H, s), 2.63 (2H, m), 2.76 (1H, m), 2.85 106 (1H, m), 2.90 (3H, m), 3.57 (2H, t), 4.61 (1H, m), 6.17 (1H, m), 6.25 (2H, s) ), 6.81 (1H, m), 6.92 (1H, m), 7.13 (1H, m), 7.27 (1H, m), 7.36 (1H, m), 7.60 (2H, m). LRMS: m / z APCl 581 [M + H *], 579 [MH "] The compound was isolated as a pale brown foam: 1 H NMR (400MHz, CD3OD) d -0.15 (3H, s), -0.01 (3H, s), 0.85 (9H, s), 1.06 (3H, d), 107 2.63 (2H, m), 2.77 (1H, m), 2.85 (1H, m), 2.95 (1H, m), 3.13 (2H, t), 3.63 (2H, t), 4.61 (1H, m), 6.16 (1H, m), 6.24 (2H, s) , 7.28 (1H, m), 7.36 (2H, m), 7.51 (2H, m), 7.65 (3H, m). The compound was isolated in the form of a pale brown foam. 1 H NMR (400MHz, CD 3 OD) d -0.15 (3H, s), -0.01 (3H, s), 0.85 (9H, s), 1.05 (3H, d), 2.63 ( 2H, m), 2.75 (1H, m), 2.85 (2H, m), 3.41 108 (2H, t), 3.52 (2H, t), 4.61 (1H, m), 6.17 (1H, m), 6.25 (2H, s), 7.27 (H, m), 7.36 (3H, m), 7.48 (3H, m), 7.62 (1H, m), 7.75 (1H , m), 7.85 (1H, m), 8.26 (1H, m). LRMS: m / z APCl 599 [M + H *], 597 [M-H "]. 15 20 Preparation 125 2- (4-Methoxy-2,3-dimethyl-phenyl) -ethylamine A mixture of (4-methoxy-2,3-dimethyl-phenyl) -acetonitrile (200 mg, 1.14 mmol) and Raney® nickel (50 mg) in 2 M methanolic ammonia (10 ml) was stirred under a pressure of 413.57 kPa (60 psi) of hydrogen gas at room temture for 18 hours. TLC analysis showed that all of the starting material had not been consumed, so that more Raney® nickel (50 mg) in 2 M methanolic ammonia (10 ml) was added. The reaction mixture was stirred under a pressure of 413.57 kPa (60 psi) of hydrogen gas for a further 18 hours at room temture and then filtered through Arbocel®. The filtrate was concentrated in vacuo and the residue was purified by column chromatography on silica gel, eluting with dichloromethane: methanol: 0.88 ammonia, 100: 0: 0 to 90: 10: 1 to yield the title product in the form of a pale brown solid, 233 mg. 1 H NMR (400MHz, CDCl 3) d: 6.96 (1H, d), 6.66 (1H, d), 3.80 (3H, s), 2.96-2.84 (2H, m), 2 , 81-2.73 (2H, m), 2.22 (3H, s), 2.17 (3H, s), 1.63 (2H, s) ppm LRMS APCl m / z 180 [M + H] + Preparadón 126 2- (2,3-Dimetil-phenyl) -ethylamine A mixture of 2,3-dimethylphenylacetonitrile (J. Org Chem, 51 (26), 5157-60; 1986), (190 mg, 1.31 mmol) and Raney® nickel (100 mg) in ammonia 2M methanolic (5 ml) was stirred under a pressure of 344.64 kPa (50 psi) of hydrogen gas for 4 days. Then, the mixture was filtered through Arbocel® and concentrated in vacuo to yield the title compound as a solid, 130 mg. 1 H NMR (400MHz, CDCl 3) d: 7.02-6.94 (3H, m), 2.26-2.13 (10H, m) ppm LRMS ESI m / z 150 [M + H] + Preparation 197 2 - (2-Chloro-4-fluoro-phenyl) -ethylamine Sodium borohydride was added in portions (1.73 g, 45.51 mmol) to a solution of 2-chloro-4-fluorophenylacetonitrile (1.04 g, 6.15 mmol) and cobalt (II) chloride hexahydrate (2, 18 g, 9.22 mmol) in methanol (30 ml) and the mixture was stirred at room temperature for 3 hours. Then, the suspension was filtered through Celite, concentrated in vacuo and the residue was partitioned between 1 M hydrochloric acid (40 ml) and dichloromethane (40 ml). The aqueous phase was separated, basified to pH 11 with a 1 M ammonia solution and extracted with dichloromethane (2 x 40 ml). The combined organic solution was washed with brine (30 ml), dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography on silica gel, eluting with dichloromethane: methanol: 0.88 ammonia, 100: 0: 0 to 98: 2: 0.2, to produce the title compound as a yellow oil, 350 mg. 1 H NMR (400MHz, CDCl 3) d: 7.30 (1H, dd), 7.17 (1H, dd), 6.99 (1 H, m), 2.86 (4H, m) ppm LRMS APCl m / z 174 [M + H] + Preparation 128 2- (5-Chloro-2-methoxy-phenyl) -ethylamine Chlorotrimethylsilane (2 mL, 16 mmol) was added dropwise to lithium borohydride (2 M in tetrahydrofuran, 4 mL, 8 mmol). Then, a solution of 2-methoxy-5-chlorophenylacetonitrile (312 mg, 4 mmol) in tetrahydrofuran (2 ml) was added at 0CC and the mixture was allowed to stir for 24 hours while heating to room temperature. Then, the mixture was diluted with methanol (20 ml) and concentrated in vacuo. The residue was taken up in a 20% potassium hydroxide solution (20 ml), extracted with dichloromethane (3 x 20 ml) and the combined organic solution was dried over magnesium sulfate and concentrated in vacuo. The residue was purified by column chromatography using an Isolute® SCX-2 cartridge, eluting with methanol followed by 1M ammonia in methanol, to give an oily residue. The oil was triturated with diethyl ether to yield the title compound, 485 mg. 1 H NMR (400MHz, CDCl 3) d: 7.11-7.00 (2H, m), 6.75-6.65 (1H, m) 3.72 (3H, s), 2.90-2.80 (2H, m), 2.70-2.60 (2H, m) ppm Preparation 129 2- (5-Chloro-2-hydroxy) phenyl) -ethylamine The amine of preparation 128 (66 mg, 0.36 mmol) was dissolved in 48% aqueous HBr and heated to 80 ° C with stirring for 12 hours. The reaction was cooled to room temperature and the solvent was removed in vacuo to give a brown gum. This gum was dissolved in methanol (5 ml) and purified by ion exchange column to yield the title compound as a brown gum, 26 mg. 1 H NMR (400MHz, CDCl 3) d: 2.70 (2H, t), 2.90 (2H, t), 6.70 (1H, d), 6.98 (1H, m), 7.02 (1H , s) ppm LRMS APCl m / z 172 [M + H] + Preparation 130 2- (5-Fluoro-2-methyl-phenyl) -ethylamine This compound was prepared using the method of preparation 128 and the appropriate nitrile. 1 H NMR (400MHz, CDCl 3) d: 7.07 (1H, m), 6.83 (2H, m), 2.97 (2H, t), 2.78 (2H, m) 2.27 (3H, s) ppm LRMS APCl m / z 154 [M + H] + Preparation 131 (tere-butyl 3-iodobenzyl) carbamate A suspension of 3-iodobenzylamine hydrochloride (4.95 g, 18.4 mmol) in dichloromethane (100 ml) was treated with triethylamine (3.1 ml, 22 mmol) and di-t-butyl dicarbonate (4.40 g). g, 20 mmol) and the resulting solution was allowed to stir at room temperature under a nitrogen atmosphere for 1.5 hours. The reaction mixture was washed with 2M hydrochloric acid (30 ml), water (30 ml), dried (sodium sulfate) and the solvent removed in vacuo to give the title compound as a colorless solid (6, 43 g). 1HNMR (400MHz, CDCl 3) d: 1, 46 (s, 9H), 4.21-4.30 (m, 2H), 4.79-4.89 (s a, 1H), 7.06 (dd, 1H), 7.25 (d, 1H), 7.60 (d, 1H), 7.63 (s, 1H) ppm. MS (electrospray) m / z 332 [M-H] ", 356 [M + Na] + Preparation 132 tere-butyl [(4'-hydroxybiphenyl-3-yl) methyl] carbamate A solution of the iodide from preparation 131 (0.75 g, 2.25 mmol), 4-hydroxyphenylboronic acid (0.62 g, 4.50 mmol), 1,1-bis (diphenylphosphine) ferrocenyl palladium chloride ( 11) (0.11 g, 0.14 mmol), in N, N-dimethylformamide (14 ml) was treated with 2 M aqueous sodium carbonate (4 ml) and the resulting mixture was heated to 80 ° C under an atmosphere of nitrogen for 16 hours. The solvent was removed under reduced pressure and the residue was purified by column chromatography on silica gel eluting with ethyl acetate: pentane (1: 3) to give the title compound as a pale pink crystalline solid (0.73). g). 1HNMR (400MHz, CDCl 3) d: 1.47 (s, 9H), 4.33-4.41 (m), 4.87-4.94 (sa, 1H), 6.89 (d, 2H), 7.21 (d, 1H), 7.37 (dd, 1H), 7.43-7.45 (m, 4H) ppm. MS (electrospray) m / z 298 [M-H] ", 322 [M + Na] + Preparation 133 3- (aminomethyl) biphenyl-4-ol hydrochloride The phenol from Preparation 132 (0.73 g, 2.43 mmol) was treated with 4 M HCl in dioxane (6 mL, 24.3 mmol) and the resulting solution was allowed to stir at room temperature for 3 hours. The solvent was removed in vacuo to give the title compound as a colorless solid. 1 H NMR (400MHz, CD3OD) d: 4.17 (s, 2H), 6.87 (d, 2H), 7.34 (d, 1H), 7.45-7.50 (m, 3H), 7.61 (d, 1H), 7.65 (s, 1H) ppm. MS (electrospray) m / z 198 [M-H] ", 200 [M + H] + Preparation 134 2- (3-Chloro-2-hydroxy-phenyl) -ethylamine Prepared in accordance with the procedure described in DE1959898. Preparation 135 3 - [(2R) -2-Aminopropyl) phenyl] propanoate methyl Prepared according to the procedure used for preparation 22, using [3 - ((2 / *?) - 2- {[[(1 / *?) - 1-phenylethyl] amino} propyl) phenyl hydrochloride ] methyl propanoate (Preparation 136) to give the title compound as a brown oil. 1 H NMR (400MHz, CD3OD): d = 7.21-7.17 (1H, t), 7.03-7.01 (3H, m), 3.61 (3H, s), 3.11-3 , 03 (1H, m), 2.91-2.87 (2H, t), 2.64-2.54 (4H, m), 1.07-1.05 (3H, d) ppm.

LRMS (electrospray): m / z [M + Hf 222. Preparation 136 [3 - ((2R) -2- { [(1?) - 1-phenylethyl] amino} propyl) phenyl] propanoate hydrochloride of methyl Prepared according to the procedure used for preparation 23, using methyl 3- [3- (2-oxopropyl) phenyl] propanoate (Preparation 137) to give the title compound as a white crystalline solid. 1 H NMR (400MHz, CD 3 OD): d = 7.54-7.47 (5H, m), 7.23-7.19 (1H, t), 7.12-7.10 (1H, d), 6 , 92-6.91 (2H, d), 4.64-4.59 (1H, c), 3.61 (3H, s), 3.34-3.29 (1H, m), 3.20 -3.12 (1H, m), 2.89-2.85 (2H, t), 2.62-2.56 (3H, m), 1.71-1, 69 (3H, d), 1 18-1.16 (3H, d) ppm. LRMS (electrospray): m / z [M + H] + 326. Preparation 137 3- [3- (2-Oxopropyl) phenyl] propanoate methyl A suspension of methyl (2 £) -3- [3- (2-oxopropyl) phenyl] acrylate (5.00 g, Preparation 138) and 10% palladium on carbon (500 mg) in ethanol (50 ml) was stirred under a hydrogen atmosphere (413.57 kPa (60 psi)) at room temperature for 16 hours. The catalyst was removed by filtration through arbocel and the filtrate was concentrated in vacuo to give the title compound as a pale yellow oil which was used without further purification. 1 H NMR (400MHz, CD3OD): d = 7.27-7.23 (1H, c), 7.11-7.09 (1H, d), 7.05-7.04 (2H, d), 3.66 (5H, s), 2.96-2.92 (2H, t), 2.64-2.60 (2H, t), 2.14 (3H, s) ppm. LRMS (electrospray): m / z [M + Naf 243, [M-H "] 219. Preparation 138 (2 £) -3- [3- (2-oxopropyl) phenyl] methyl acrylate A solution of 3-bromophenylacetone (50.0 g, 235 mmol), methyl acrylate (40.4 g, 469 mmol), palladium (II) acetate (7.9 g, 35.2 mmol), tri-oAll tolylphosphine (21.4 g, 70.4 mmol) and triethylamine (82 ml) in acetonitrile (900 ml) was heated to reflux in a nitrogen atmosphere for a period of 16 hours. The reaction mixture was cooled to room temperature and the solvent was removed in vacuo. Purification by flash column chromatography eluting with pentane: ethyl acetate (90:10 changing to 70:30 by volume) gave the title compound as an orange oil (54.3 g). 1 H NMR (400MHz, CD3OD): d = 7.66-7.62 (1H, d), 7.41-7.39 (1H, d), 7.34-7.31 (2H, t), 7.20-7.18 (1H, d), 6.43-6.39 (1H, d), 3.77 (3H, s) , 3.70 (2H, s), 2.15 (3H, s) ppm. LRMS (electrospray): m / z [M + Na] +241, [MH] "217. Preparation 139 3- (3-. {2- [2- (3,5-bis-benzyloxy-) methyl ester phenyl) -2- (tert-butyl-dimethyl-silanyloxy) -ethylamino] -propyl.} - phenyl) -propionic The bromide from Preparation 11 (3.46 g, 6.56 mmol) and the amine from Preparation 135 (2.90 g, 13.1 mmol) were combined in dichloromethane (50 mL) and the solvent was removed in vacuo. . The resulting oil was heated at 90 ° C for 12 hours and cooled to room temperature, the orange oil was stirred in ether (200 ml) for 5 minutes and the ether layer was removed by decanting with caution. The remaining orange oil was stirred with ether (2 x 200 ml) twice more and the ether layers were combined and the solvent was removed in vacuo. The resulting orange oil was purified by flash column chromatography eluting with dichloromethane: methanol: ammonia (100: 0: 0 and then 96: 4: 0.4) to yield the title compound as a golden oil (3.40 g). 1H NMR (400MHz, CD3OD) d: -0.20 (3H, s), -0.05 (3H, s), 0.82 (9H, s), 1, 03 (3H, d), 2.52-2.65 (5H, m), 2.79-2.94 (4H, m), 3.60 (3H, s), 4.66 (1H, m), 5.04 (4H, m), 6.49 (2H, s), 6.53 (1H, m), 6.89-6.96 (2H, m), 6 , 99 (1H, m), 7.15 (1H, m), 7.23-7.44 (10H, m); LRMS APCl m / z 668 [M + H] + Preparation 140 3- (3 { 2- [2- (3,5-bis-benzyloxy-phenyl) -2- (tert-butyl-dimethyl) hydrochloride -synyloxy) -ethylamino] -propyl.}. -phenyl) -propionic The ester of preparation 139 (3.40 g, 5.10 mmol) in tetrahydrofuran (15 ml) was treated with lithium hydroxide (1 M, 11.2 ml, 11.21 mmol). Dioxane (50 ml) and water (10 ml) were added and the resulting solution was stirred for 20 hours. The solution was acidified to pH 1 with hydrochloric acid (1 N) and extracted with dichloromethane (3 x 150 ml). The organic extracts were washed with brine (50 ml) and dried (magnesium sulfate). Filtration and evaporation of the solvent left a white foam (3.5 g, 91%) 1 H NMR (400MHz, CD3OD) d: -0.13 (3H, s), 0.06 (3H, s), 0.86 (9H, s), 1.03 (3H, d), 2.58 (2H, t), 2.75 (1H, m), 2.88 (2H, t), 3.06 (1H, m) , 3.23 (1H, m), 3.34 10 (1H, m), 3.55 (1H, m), 5.04-5.16 (5H, m), 6.66 (3H, m) , 7.06 (1H, m), 7.12 (1H, s), 7.18 (1H, m), 7.23-7.47 (11H, m); LRMS APGI m / z 655 [M + H] + Preparation 141 3- (3- {2- [2- (tert-Butyldimethylsilanyloxy) -2- (3,5-dihydroxyphenyl) ethylamino] propyl} phenyl} propionic acid Prepared according to the procedure used for preparation 13, using 3- (3. {2- [2- (3,5-bis-benzyloxy-phenyl) -2- (tert-butyl-dimethyl-) hydrochloride. silanyloxy) -ethylamino] -propyl.} - phenyl) -propionic (Preparation 140) to give the title compound as a yellow solid. 1 H NMR (400MHz, CD 3 OD) d: -0.06 (3H, s), 0.08 (3H, s), 0.86 (9H, s), 1.22 (3H, d), 2.54 ( 2H, t), 2.74 (1H, m), 2.90 (2H, t), 3.15 (1H, m), 3.26 (1H, m), 3.45 (1H, m), 4.90 (1H, m), 6.26 (1H, m), 6.35 (2H, s), 7.02 (1H, m), 7.08 (1H, s), 7.16 (1H , m), 7.24 (1H, m); LRMS APCl m / z 474 [M + H] + Preparation 142 3- (3- { 2- [2- (tert-Butyld-methyl-silanyloxy) -2- (3,5-dihydroxyphenyl) ethylamino] propyl.}. phenyl) -? / - (2-chlorobenzyl) proponamide Prepared according to the procedure used for preparation 34, using preparation 141, 2-chlorobenzylamine and N, N-dimethylacetamide in place of N,? / - dimethylformamide. 1 H NMR (400MHz, CD3OD) d: -0.15 (3H, s), 0.01 (3H, s), 0.84 5 (9H, s), 1.03 (3H, d), 2.47. -2.58 (3H, m), 2.60-2.70 (2H, m), 2.80-2.95 (4H, m), 4.41 (2H, m), 4.59 (1H , m), 6.16 (1H, m), 6.24 (2H, s), 6.95 (2H, m), 7.02-7.08 (2H, m), 7.13-7, 25 (3H, m), 7.36 (1H, m); LRMS APCl m / z 598 [M + H] + Preparation 143 3- (3- { 2- [2- (tert-Butyldimethylsilanyloxy) -2- (3,5-dihydroxyphenyl) etimam or not] propyl.}. phenyl) - / V- (2,6-dichlorobenzyl) propionamide Prepared in accordance with the procedure used for preparation 34, using preparation 141, 2,6-dichlorobenzylamine and N, N-dimethylacetamide in place of? /,? / - dimethylformamide. 1 H NMR (400MHz, CD3OD) d: -0.15 (3H, s), 0.00 (3H, s), 0.85 (9H, s), 1, 03 (3H, d), 2.44-2.57 (3H, m), 2.60-2.68 (2H, m), 2.80-2.90 (4H , m), 0 4.55-4.65 (3H, m), 6.16 (1H, m), 6.24 (2H, s), 6.91 (1H, m), 6.94 (1H , m), 7.01 (1H, m), 7.12 (1H, m), 7.26 (1H, m), 7.37-7.41 (2H, m); LRMS APCl m / z 631 [M + H] + Preparation 144 3- (3- { 2- [2- (tert-Butyldimethylsilanyloxy) -2- (3,5-dihydroxyphenyl) ethylami-no] propyl} phenyl) -1 - (3,4-dihydro- 1 H-isoquinolin-2-yl) -propan-1 -one Prepared according to the procedure used for preparation 34, using preparation 141, 1, 2,3,4-tetrahydroisoquinoline and V,? / - dimethylacetamide in place of? /, N-dimethylformamide. 1 H NMR (400MHz, CD 3 OD) d: -0.15 (3H, s), -0.01 (3H, s), 0.85 (9H, s), 0.99 (3H, m), 2.42. -2.64 (3H, m), 2.68-2.96 (8H, m), 3.63-3.76 (2H, m), 4.55-4.67 (3H, m), 6 , 16 (1H, m), 6.23 (2H, s), 6.81-7.21 (8H, m); LRMS APCl m / z 590 [M + H] + Preparation 145 2- (3- { 2- [2- (tert-Butyldimethylalanyloxy) -2- (3,5-dihydroxyphenyl) ethylamide no] propyl.}. phenyl) -? / - (2-chloro-4-fluorobenzyl) acetamide Prepared according to the procedure used for preparation 142, using the acid of preparation 33 and 2-chloro-4-fluorobenzylamine. 1 H NMR (400MHz, CD 3 OD) d: -0.02 (3H, d), 0.00 (3H, s), 0.84 (9H, s), 1.04 (3H, d), 2.54- 2.70 (3H, m), 2.86-2.93 (2H, m), 3.53 (2H, s), 4.41 (1H, s), 4.46 (1H, s), 4 , 60-4.63 (1H, m), 6.14-6.15 (1H, m), 6.22 (2H, d), 6.97-7.50 (7H, m), 7.64 -7.69 (1H, m); LRMS APCl m / z 601 [M + H +]. Prepare 14fi? / - (4-Bromobenzyl) -2- (3- { 2- [2- (tert-Butyldimethylsilanyloxy) -2- (3,5-dihydroxyphenyl) ethylamino] -2-methylpropyl. phenyl) acetamide Prepared according to the procedure used for preparations 34, using the acid of preparation 33 and 4-bromobenzylamine. 1 H NMR (400MHz, CD3OD) d: -0.23 (s, 3H), -0.04 (s, 3H), 0. 82 (s, 9H), 1.07 (d, 6H), 2.63-2.77 (m, 3H), 2.84 (t, 1 H), 3.56 (s, 2H), 4.31 (s, 2H), 4.57-4.63 (m, 1H), 6.18 (t, 1H), 6.36 (s, 2H), 7.08 (t, 2H), 7.12- 7.18 (m, 3H), 7.21 (t, 1H), 7.42 (d, 2H); LRMS ESI m / z 643 [M + H] +.

Preparation 147 2- (3- { 2- [2- (tert-Butyldimethylsilanyloxy) -2- (3,5-dihydroxyphenyl) ethylamino] -2-methylpropyl}. Phenyl) -? / - (3, 4-dimethylphenyl) acetamide Prepared according to the procedure used for preparations 34, using the acid of preparation 33 and 3,4-dimethylaniline. 1 H NMR (400MHz, CD 3 OD) d: -0.17 (s, 3H), -0.03 (s, 3H), 0.81 (s, 9H), 1, 07 (d, 5 6H), 2, 22 (d, 6H), 2.61-2.77 (m, 3H), 2.83 (t, 1H), 3.61 (s, 2H), 4.57-4.61 (m, 1H) , 6.18 (s, 1H), 6.29 (s, 2H), 7.06 (t, 2H), 7.18 (s, 1H), 7.21-7.25 (m, 3H), 7.31 (s, 1H); LRMS ESI m / z 643 [M + H] +. Preparation 148 2- (3- { 2- [2- (tert-Buty'ldimethylsilanyloxy) -2- (3,5-dihydroxyphenyl) ethylami-no] propyl} phenyl) - / V- (2,3 -dimethylbenzyl) acetamide Prepared according to the procedure used for preparations 34, using the acid of preparation 45 and 2.3- dimethylbenzylamine and? /,? / - dimethylacetamide instead of? /,? / - dimethylformamide. 1 H NMR (400MHz, CD 3 OD) d: -0.17 (3H, s), -0.04 (3H, s), 0.80 (9H, s), 0.97 (3H, d), 2.09 (3H, s), 2.21 (2.46-2.51 (1H, dd), 2.56-2.65 (2H, m), 2.76-2.84 (2H, m), 3 , 45 (2H, s), 4.32 (2H, s), 4.53 (1H, dd), 5.44 (2H, s), 6.09 (1H, t), 6.17 20 (1H , 1), 6.18 (1H, s), 6.93-7.17 (7H, m); LRMS APCl m / z 578 Preparation 149 2- (3- { 2- [2- (tert-Butyldimethylsilanyloxy) -2- (3,5-dihydroxyphenyl) ethylamino] propyl} phenyl) -? / - (4-fluorobenzyl) acetamide Prepared according to the procedure used for preparations 34, using the acid of preparation 45 and 4-fluorobenzylamine and? /,? / - dimethylacetamide in place of? /,? / - dimethylformamide. 1 H NMR (400MHz, CD 3 OD) d: -0.17 (3H, s), -0.04 (3H, s), 0.80 (9H, s), 0.98 (3H, d), 2.47. (1H, dd), 2.55-2.64 (H, m), 2.77-2.84 (2H, m), 3.46 (2H, s), 4.28 (2H, s), 4.53 (1H, dd), 6.09-6.11 (1H, m), 6.17 (1H, s), 6.18 (1H, s), 6.91-7.02 (4H, m), 7.05-7.08 (1H, m), 7.13 (1H, t), 7.17-7.23 (2H, m); LRMS APCl m / z 567 [M + H] +.

Preparation 150 2- (3- { 2- [2- (tert-Butyldimethylsilanyloxy) -2- (3,5-dihydroxyphenyl) ethylamino] propyl} phenyl) -1 - (4-pyridin-2- il-piperazin-1-yl) ethanone Prepared according to the procedure used for preparations 34, using the acid of preparation 45 and 1-pyridin-2-ylpiperazine and? /, / V-dimethylacetamide in place of? /,? / - dimethylformamide. 1 H NMR (400MHz, CD 3 OD) d: -0.12 (3H, s), 0.00 (3H, s), 0.80 (9H, s), 1.12 (3H, 5 d), 2.66 (1H, dd), 2.88-2.93 (2H, m), 3.04-3.10 (1H, m), 3.15 (1H, dd), 3.32-3.43 ( 4H, m), 3.60-3.66 (4H, m), 3.73-3.79 (2H, m), 4.81-4.85 (1H, m), 6.18 (1H , t), 6.25 (1 H, s), 6.26 (1H, s), 6.60-6.63 (1H, m), 6.72 (1H, d), 7.04-7 , 07 (2H, m), 7.12 (1H, d), 7.23 (1H, t), 7.46 (1H, dt), 8.00 (1H, d); LRMS APCl m / z 606 [M + H] +. Preparation 151 2- (3- { 2- [2- (tert-Butyldimethylsilanedioxy) -2- (3,5-dihydroxyphenyl) ethylami-no] -2-methylpropyl.} Phenyl) -? / - ( 2-phenylpropyl) acetamide The title compound was prepared from the compound of preparation 33 and the appropriate amine using the method described for preparation 34 and was isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d -0.20 (3H, s), -0.07 (3H, s), 0.74 (9H, s), 1.02 (3H, d), 1.09 ( 3H, d), 2.62 (1H, dd), 2.79 (1H, dd), 2.88-2.97 (2H, m), 3.04 (1H, dd), 3.16-3 , 24 (1H, m), 3.27-3.88 (2H, m), 3.41 (2H, s), 4.74 (1H, dd), 6.19 (1H, t), 6, 27 (1H, s), 6.28 (1H, s), 7.01-7.07 (2H, m), 7.13-7.27 (4H, m). LRMS APCl m / z 578 [M + H +]. Fjgmpln 1? / - Benzyl-2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetamide To a solution of the acid of Preparation 9 (50 mg, 0.10 mmol) and benzylamine (14 mg, 0.13 mmol) in? /,? / - dimethylformamide (1 mL) was added O- hexafluorophosphate ( 1H-benzotriazol-1-yl) -N, N, N ', N * -tetramethyluronium (50 mg, 0.13 mmol) in? /,? / - dimethylformamide (3 ml) and the reaction was stirred for 12 hours. The solvent was removed in vacuo to give the crude residue. Purification by column chromatography on silica gel using dichloromethane: methanol: 0.88 ammonia (97.5: 2.5: 0.25-90: 10: 1) gave the product desired, 17 mg (37%). 1 H NMR (400 MHz, CD 3 OD) d 1, 02 (3 H, s), 1.04 (3 H, s), 2.84-2.64 (4 H, m), 3.52 (2 H, s), 4 , 35 (2H, s), 4.53-4.57 (1H, c), 6.18 (1H, s), 6.33 (2H, s), 7.02-7.04 (2H, d), 7.12-7.28 (7H, m). LRMS: m / z APCI + 449 [MH +]. Fjp > mplns 2-1 A solution of the acid from preparation 9 (30 μmol) in N, N-dimethylformamide (100 μl) was added to the appropriate amine (HNRARB) (30 μmol) in α /, / / - dimethylformamide (100 μl) and the mixture of reaction was sealed and stirred. A solution of O-benzotriazole-1-yl-NNN'.N'-tetramethyluronium hexafluorophosphate (11.38 mg, 30 μmol) in N, N-dimethylformamide (200 μl) was added, the reaction mixture was sealed. , it was stirred and left to stand at room temperature for 4 days. The reaction mixture was purified directly by HPLC using a Feno-menex Luna C18 column (150 x 10mm, 10 μm), with a flow rate of 8 ml / min and detection at 225 nm, using the following gradient system. A- 0.05% aqueous diethylamine B-acetonitrile Each product was analyzed using a Fenomenex Luna C18 column (30 x 4.6 mm, 5 μm) with a flow rate of 2.5 ml / min using the gradient described in the table below. A- 6.5 mM 5% ammonium acetate in water: acetonitrile (95: 5) B- acetonitrile A = 3-amino-5-ethyl-1 H-pyrazole prepared as described in WO 03/048133 Fjsmpln 1? ? / - [2- (4-Chloro-phenyl) -ethyl] -3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -benzamide Ammonium fluoride (1.08 g, 29.2 mmol) was added in one portion to a stirred solution of the compound of preparation 15 (1.56 g, 2.61 mmol) in methanol (25 mL) and water (18 mL). ) at room temperature. The reaction was heated at 40 ° C for 48 hours, cooled to room temperature and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (100: 0: 0 then 95: 5: 0.5 and then 90: 0: 1) to produce the title compound in the form of a brown solid, 885 mg. 1 H NMR (400MHz, CD 3 OD) d 1.10 (3H, s), 1.16 (3H, s), 2.75 (6H, m), 3.62 (2H, 15 m), 4.66 (1H , dd), 6.23 (1H, m), 6.40 (1H, s), 6.41 (1H, s), 7.33 (6H, m), 7.67 (2H, m). LRMS: m / z APCl 484 [M + H +]. Example 13 / V-Adamantan-1-yl-2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide Ammonium fluoride (100 mg, 2.70 mmol) was added in one portion to a stirred solution of the compound of Preparation 30 (160 mg, 0.27 mmol) in methanol (2 mL) and water (1 mL) at room temperature . The reaction was heated at 40 ° C for 12 hours, cooled to room temperature and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (93: 7: 0.7) to give the title compound as a white foam, 78 mg. 1 H NMR (400MHz, CD3OD) d 1.07 (3H, d), 1.68 (6H, s), 2.01 (9H, m), 2.60 (4H, m), 2.91 (1H, m), 3.40 (2H, s), 4.50 (1H, m), 6.13 (1H, m), 6.23 (2H, s), 6.99 (1H, d), 7, 08 (1H, s), 7.10 (1H, d), 7.18 (1H, t). LRMS: m / z electrospray 479 [M + H +], 477 [M-H] '. FjemplQ 14 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -? / - [2- (3-Fluoro-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of Preparation 36 using the method described for Example 12 and isolated as a white solid. 1 H NMR (400MHz, CD3OD) d 1.11 (3H, s), 1.15 (3H, s), 2.74-2.82 (2H, m), 2.90-3.00 (4H, m ), 3.62-3.66 (2H, m), 4.61-4.66 (1H, m), 6.23-6.24 (1H, m), 6.39 (1H, s) , 6.40 (1H, s), 6.94-6.98 (1H, m), 7.03-7.07 (1H, m), 7.10-7.12 (1H, m), 7 , 29-7.43 (3H, m), 7.65-7.69 (2H, m). LRMS: m / z APCl 467 [M + H +]. Fj mpln 15 N- [2- (2-Chloro-phenyl) -ethyl] -3-. { 2- [2- (3,5-D-Hydroxy-phenyl) -2-hydroxyethylamino] -2-methyl-propyl} -benzamide The title compound was prepared from the compound of preparation 37 using the method described for example 12 and isolated as a white solid. 1 H NMR (400MHz, CD 3 OD) d 1.10 (3H, s), 1.15 (3H, s), 2.76-2.84 (2H, m), 2.88-2.96 (2H, m) ), 3.10-3.14 (2H, m), 3.66-3.70 (2H, m), 4.61-4.64 (1H, m), 6.22-6.24 (1H , m), 6.39 (1H, s), 6.40 (1H, s), 7.21-7.28 (2H, m), 7.35-7.42 (4H, m), 7, 66-7.69 (2H, m). LRMS: m / z APCl 483 [M + H +]. Example 16 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -? / - [2- (2,3-dimethyl-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of Preparation 38 using the method described for Example 12 and isolated as a white solid. 1 H NMR (400MHz, CD3OD) d 1, 14 (3H, s), 1, 19 (3H, s), 2.30 (3H, s), 2.31 (3H, s), 2.80-3, 02 (6H, m), 3.56-3.59 (2H, m), 4.63-4.67 (1H, m), 6.24-6.25 (1H, m), 6.40 ( 1H, s), 6.41 (1H, s), 6.99-7.07 (3H, m), 7.38-7.45 (2H, m), 7.68-7.72 (2H, m). LRMS: m / z APCl 477 [M + H +]. Example 17? / - [2- (2-Chloro-4-fluoro-phenyl) -ethyl] -3-. { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -benzamide The title compound was prepared from the compound of preparation 39 using the method described for example 12 and isolated as a white solid. 1 H NMR (400MHz, CD3OD) d 1.09 (3H, s), 1.15 (3H, s), 2.75- 2.83 (2H, m), 2.88-2.96 (2H, m), 3.08-3.11 (2H, m), 3.64-3.68 (2H, m), 4, 61-4.64 (1H, m), 6.22-6.23 (1H, m), 6.39 (1H, s), 6.40 (1H, s), 7.01-7.06 ( 1H, m), 7.21-7.24 (1H, m), 7.35-7.42 (3H, m), 7.65-7.68 (2H, m). LRMS: m / z APCl 501 [M + H +]. Example 18 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -? / - [2- (4-methoxy-2,3-dimethyl-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of preparation 40 using the method described for example 12 and isolated as a white solid. 1 H NMR (400MHz, CD3OD) d 1.12 (3H, s), 1, 18 (3H, s), 2.16 (3H, s), 2.30 (3H, s), 2.77-3, 00 (6H, m), 3.52-3.56 (2H, m), 3.80 (3H, s), 4.62-4.65 (1H, m), 6.23-6.24 ( 1H, m), 6.40 (1H, s), 6.41 (1H, s), 6.72-6.74 (1H, d), 7.01-7.03 (1H, d), 7 , 37-7.44 (2H, m), 7.67 (1H, s), 7.70-7.72 (1H, m). LRMS: m / z APCl 507 [M + H +]. Example 19? - (3,4-Dichloro-benzyl) -2- (3. {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl}-phenyl) -acetamide The title compound was prepared from the compound of preparation 34 using the method described for Example 12 and isolated as a white foam. H NMR (400MHz, CD3OD) d 1.02 (3H, s), 1, 04 (3H, s), 2.74 (4H, m), 3.56 (2H, s), 4.32 (2H, s), 4.54 (1H, m), 6.17 (1H, s), 6.36 (2H, s), 7.03 (1H, d), 7.15 (3H, m), 7, 22 (1H, t), 7.36 (1H, d), 7.43 (1H, d). LRMS: m / z electrospray 517 [M + H +]. Fjempln 20? / - (3,4-Dichloro-benzyl) -3-. { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -benzamide The title compound was prepared from the compound of preparation 41 using the method described for example 12 and isolated as a white solid. 1 H NMR (400MHz, CD3OD) d 1.16 (3H, s), 1.20 (3H, s), 2.83-3.01 (4H, m), 4.59 (2H, s), 4, 64-4.67 (1H, m), 6.23 (1H, m), 6.38 (1H, s), 6.39 (1H, s), 7.31-7.34 (1H, m) ), 7.41-7.55 (4H, s), 7.76-7.80 (2H, s). LRMS: m / z APCl 503 [M + H +].

Example 21? / - (4-Chloro-benzyl) -3-. { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -benzamide The title compound was prepared from the compound of preparation 42 using the method described for Example 12 and isolated as a white solid. 1 H NMR (400MHz, CD 3 OD) d 1.10 (3H, s), 1.15 (3H, s), 2.76-2.82 (2H, m), 2.90-2.96 (2H, m ), 4.59 (2H, s), 4.60-4.63 (1H, m), 6.23 (1H, m), 6.37 (1H, s), 6.38 (1H, s) , 7.34-7.45 (6H, m), 7.74-7.77 (2H, m). LRMS: m / z APCl 469 [M + H +]. Fjampln 22? / - Adamantan-1-il-3-. { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -benzamide The title compound was prepared from the compound of preparation 43 using the method described for example 12 and isolated as a white solid. 1 H NMR (400MHz, CD3OD) d 1.27 (3H, s), 1.28 (3H, s), 1.79- 1.81 (6H, m), 2.14 (3H, m), 2.21-2.22 (6H, m), 2.95-3.09 (4H, m), 4.71-4, 74 (1H, m), 6.26 (1H, m), 6.42 (1H, s), 6.42 (1H, s), 7.40-7.46 (2H, m), 7.65 (1H, s), 7.68-7.70 (1H, m). LRMS: m / z APCl 480 [M + H +]. Example 23? / - (4-Chloro-benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl .}.-phenyl) -acetamide The title compound was prepared from the compound of preparation 46 using the method described for example 12 and isolated as a white foam. 1 H NMR (400MHz, CD3OD) d 1.01 (3H, s), 1.04 (3H, s), 2.74 (4H, m), 3.53 (2H, s), 4.34 (2H, s), 4.54 (1H, m), 6.18 (1H, s), 6.34 (2H, s), 7.03 (1H, d), 7.11 (1H, s), 7, 20 (6H, m). LRMS: m / z electrospray 483 [M + H +]. Example 24? / - (4-Trifluoromethoxybenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -2-methyl-propyl}. phenyl) -acetamide The title compound was prepared from the compound of preparation 47 using the method described for example 12 and isolated as a white foam. 1 H NMR (400MHz, CD3OD) d 1.01 (3H, s), 1.03 (3H, s), 2.74 (4H, m), 3.53 (2H, s), 4.37 (2H, s), 4.54 (1 H, m), 6.18 (1H, s), 6.34 (2H, s), 7.03 (1H, d), 7.20 (7H, m). LRMS: m / z electrospray 533 [M + H +]. Example 25 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - pyridin-2 -ylmethyl-acetamide The title compound was prepared from the compound of preparation 48 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400MHz, CD3OD) d 1.01 (3H, s), 1.03 (3H, s), 2.74 (4H, m), 3.59 (2H, s), 4.45 (2H, s), 4.54 (1H, m), 6.16 (1H, s), 6.35 (2H, s), 7.05 (1H, d), 7.20 (5H, m), 7, 72 (1H, t), 8.42 (1H, d). LRMS: m / z electrospray 450 [M + H +].

Fjfimpln 26? / - (3,4-Dichloro-benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -propyl}. phenyl) -acetamide The title compound was prepared from the compound of Preparation 49 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400MHz, CD3OD) d 1.01 (3H, d), 2.58 (1H, m), 2.64 (2H, m), 2.78 (1 H, m), 2.90 (1 H, m), 3.56 (2H, s), 4.37 (2H, s), 4.54 (1H, m), 6.18 (1H, s), 6.25 (2H, s), 7.03 (5H, m), 7.38 (2H, m). LRMS: m / z electrospray 503 [M + H +]. Example 27? / - (Benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -phenyl) -acetamide The title compound was prepared from the compound of preparation 50 using the method described for example 12 and isolated as a brown foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 06 (3 H, d), 2.57 (1 H, m), 2.68 (2 H, m), 2.81 (1 H, m), 2.90 (1 H, m), 3.53 (2H, s), 4.35 (2H, s), 4.52 (1H, m), 6.16 (1H, m), 6.25 (2H, s), 7, 01 (1H, m), 7.08 (1H, s), 7.13 (1H, m), 7.20 (6H, m). LRMS: m / z APCl 435 [M + H *], 433 [M-H]. Example 28? / - Cyclohexylmethyl-2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 51 using the method described for example 12 and isolated as a brown foam. 1 H NMR (400MHz, CD3OD) d 0.88 (2H, m), 1, 06 (3H, d), 1.18 (3H, m), 1.42 (1H, m), 1.68 (5H, m), 2.58 (1H, m), 2.70 (2H, m), 2.81 (1H, m) , 2.92 (1 H, m), 2.99 (2H, d), 3.46 (2H, s), 4.53 (1H, m), 6.15 (1H, m), 6.25 (2H, s), 7.00 (1H, m), 7.08 (2H, m), 7.19 (1H, m). LRMS: m / z APCl 441 [M + H +], 439 [MH "] Example 29 1- (3,4-Dihydro-1H-isoquinolin-2-yl) -2- (3-. {2- 2- [ 2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -ethanone The title compound was prepared from the compound of Preparation 52 using the method described for Example 12 and isolated as a brown foam. 1 H NMR (400MHz, CD 3 OD) d 1.00 (3H, m), 2.57 (7H, m), 3.70 (1H, m), 3.80 (3H, m), 4.50 (1H, m), 4.68 (2H, d), 6.16 (1H, m), 6.26 (2H, s), 7.01 (7H, m). LRMS: m / z APCl 461 [M + H +], 459 [MH "] Example 30? / - Benzyl-2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2 -hydroxy-ethylamino] -propyl.}. -phenyl) -? / - methyl-acetamide The title compound was prepared from the compound of Preparation 53 using the method described for Example 12 and isolated as a brown foam. 1 H NMR (400MHz, CD3OD) d 1.05 (3H, d), 2.62 (3H, m), 2.88 (5H, m), 3.78 (2H, m), 4.50 (1H, m), 4.58 (2H, m), 6.16 (1H, m), 6.26 (2H, s) , 7.01 (2H, m), 7.07 (2H, m), 7.20 (5H, m).

LRMS: m / z APCl 449 [M + H +], 447 [MH "] Example 31 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.}. -phenyl) -? / - (2-hydroxy-benzyl) -acetamide The title compound was prepared from the compound of Preparation 54 using the method described for Example 12 and isolated as a brown foam. 1 H NMR (400MHz, CD 3 OD) d 1, 05 (3H, d), 2.56 (1H, m), 2.68 (2H, m), 2.81 (2H, m), 3.52 (2H, s), 4.34 (2H, s), 4.53 (1H, m), 6.16 (1H, m), 6.25 (2H, s), 6.76 (2H, m), 7, 00 (1H, m), 7.08 (4H, m), 7.18 (1H, m). LRMS: m / z APCl 451 [M + H +], 449 [MH "] Example 32? / - (4-Cyano-benzyl) -2- (3-. {2- 2- (3,5- dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 55 using the method described for Example 12 and isolated in shape of a white solid. 1 H NMR (400 MHz, CD 3 OD) d 1, 13 (3 H, s), 1, 15 (3 H, s), 2.85 (4 H, m), 3.61 (2 H, s), 4.47 (2 H, s), 4.62 (1H, m), 6.23 (1H, m), 6.38 (2H, s), 7.11 (1H, d), 7.21 (2H, s), 7 , 28 (1 H, m), 7.42 (2H, d), 7.67 (2H, d). LRMS: m / z electrospray 474 [M + H +], 472 [MH "] Example 33 - (2,4-Dichloro-benzyl) -2- (3- { 2- [2- (3,5- dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -acetamide The title compound was prepared from the compound of Preparation 56 using the method described for Example 12 and isolated as a white solid. 1 H NMR (400 MHz, CD 3 OD) d 1.12 (3 H, s), 1, 13 (3 H, s), 2.85 (4 H, m), 3.60 (2 H, s), 4.46 (2 H, s), 4.62 (1 H, m), 6.23 (1H, m), 6.38 (2H, s), 7.11 (1H, d), 7.20 (2H, m), 7.28 (3H, m), 7.47 (1H, s). LRMS: m / z electrospray 517 [M + H +], 515 [MH "]. Fjempln 34? / - (Benzyl) -2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylammonyl] -2-methyl-propyl.} - phenyl) -acetamide Triethylamine trihydrofluoride (42 μL, 0.25 mmol) was added in one portion to a stirred solution of the compound of Preparation 57 (130 mg, 0.23 mmol) in methanol (4 mL) at room temperature. The reaction was stirred for 12 hours and then the pH was adjusted to pH 7 using trifluoroacetic acid. The solvent was removed in vacuo and the residue was purified by column chromatography on silica gel eluting with dichloromethane: methanol: 880 ammonia (95: 5: 0.5 and then 90: 10: 1) to yield the title compound. title in the form of a white foam, 80 mg. 1 H NMR (400MHz, CD 3 OD) d 1.09 (3H, s), 1.10 (3H, s), 2.79 (4H, m), 3.53 (2H, s), 4.37 (2H, s), 4.55 (1H, m), 6.18 (1H, t), 6.33 (2H, s), 7.04 (1H, d), 7.13 (1H, s), 7 , 16 (1H, d), 7.25 (6H, m). LRMS: m / z electrospray 449 [M + H +]. Example 35? / - (2-Chlorobenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} - phenol) -acetamide The title compound was prepared from the compound of Preparation 58 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1.06 (3H, s), 1, 08 (3H, s), 2.70 (3H, m), 2.83 (1 H, m), 3.57 (2H, s), 4.43 (2H, s), 4.56 (1H, m), 6.18 (1H, s), 6 , 34 (2H, s), 7.04 (1H.10 d), 7.18 (6H, m), 7.17 (1H, d). LRMS: m / z electrospray 483 [M + H +]. Fjempln 36? / - (3-Methoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -acetamida The title compound was prepared from the compound of Preparation 59 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1.06 (3H, s), 1, 08 (3H, s), 2.72 (4H, m), 3.53 (2H, s), 3.68 (3H, s), 4.33 (2H, s), 4.56 (1H, m), 6.18 (1H, m), 6.32 (2H, s), 6.78 (2H, m), 7 , 03 (1 H, d), 7.18 (5H, m). LRMS: m / z electrospray 479 [M + H +].

? / - (Cyclohexylmethyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy "ethylamino] -2-methyl-propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 60 using the method described for example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 0.91 (2H, m), 1, 06 (3H, s), 1, 08 (3H, s), 1, 18 (3H, m), 1, 44 (1H, m), 1.70 (5H, m), 2.70 (3H, m), 2.84 (1H, m), 3.02 (2H, d), 3.46 (2H, s), 4, 58 (1H, m), 6.17 (1H, t), 6.34 (2H, s), 7.07 (1H, d), 7.17 (2H, d), 7.22 (1H, t). LRMS: m / z APCl 455 [M + H +]. Fjftmpln 38 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - phenethyl -acetamide The title compound was prepared from the compound of preparation 61 using the method described for Example 34 and isolated as a white foam. H NMR (400MHz, CD3OD) d 1, 07 (3H, s), 1, 08 (3H, s), 2.73 (6H, m), 3.42 (2H, m), 3.47 (2H, s), 4.55 (1H, m), 6.17 (1H, s), 6.33 (2H, s), 7.15 (8H, m). LRMS: m / z electrospray 463 [M + H +], 461 [M-H "].

Fjfimpln 39 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (4- chlorphenethyl) -acetamide The title compound was prepared from the compound of preparation 62 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1, 07 (3H, s), 1.08 (3H, s), 2.73 (6H, m), 3.43 (2H, m), 3.42 (2H, s), 4.55 (1H, m), 6.17 (1H, s), 6.36 (2H, s), 7.08 (5H, m), 7.21 (3H, m). LRMS: m / z electrospray 497 [M + H +], 495 [MH "]. Fjampln 40 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.}. -phenyl) -? / - (4-phenylphenethyl) -acetamide The title compound was prepared from the compound of preparation 63 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1.04 (3H, s), 1, 05 (3H, s), 2.73 (6H, m), 3.43 (4H, m), 4.55 (1H, m), 6.18 (1H, m), 6.33 (2H, s), 7.08 (3H, m), 7.21 (3H, m), 7.31 (1H, t), 7, 42 (2H, m), 7.51 (2H, d), 7.56 (2H, d). LRMS: m / z electrospray 540 [M + H +]. Example 41 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (4 ' -hydroxy-biphenyl-3-ylmethyl) -acetamide The title compound was prepared from the compound of preparation 64 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1.07 (3H, s), 1, 08 (3H, s), 2.73 (2H, m), 2.85 (2H, m), 3.57 (2H, s), 4.42 (2H, s), 4.58 (1 H, m), 6.19 (1H, m), 6.33 (2H, s), 6.83 (2H, d), 7 , 07 (1H, d), 7.13 (2H, d), 7.23 (2H, m), 7.38 (5H, m). LRMS: m / z electrospray 541 [M + H +], 539 [MH "] Example 42? / - Cycloheptyl-2- (3-. {2- [2- (3,5-dihydroxy-phenyl) -2 -hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 65 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1, 07 (3H, s), 1, 08 (3H, s), 1, 58 (10H, m), 1, 86 (2H, m), 2.73 (4H, m), 3.44 (2H, s), 3.80 (1 H, m), 4.58 (1H, m), 6.18 (1 H, m), 6.32 (2H, s), 7.05 (1H, d), 7.15 (2H, d), 7.23 (1H, t). LRMS: m / z electrospray 455 [M + H +], 453 [MH "]. Example 43 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.}. -phenyl) -? / - phenethyl-acetamide The title compound was prepared from the compound of Preparation 66 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1.05 (3H, d), 2.78 (7H, m), 3.40 (4H, m), 4.52 (1H, m), 6.13 (1H, m), 6.24 (2H, s), 7.08 (9H, m). LRMS: m / z APCl 447 [MH "] Example 44 2- (3-. {2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl ) -? / - (2-methylsulfanyl-benzyl) -acetamide The title compound was prepared from the compound of preparation 67 using the method described for example 12 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 05 (3 H, d), 2.44 (3 H, s), 2.56 (1 H, m), 2.75 (4 H, m), 3.53 (2 H) , s), 4.44 (2H, s), 4.52 (1H, m), 6.13 (1H, m), 6.24 (2H, s), 7.10 (8H, m). Fjempln 45? / - (2,6-Dichloro-benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl}. phenyl) -acetamide The title compound was prepared from the compound of Preparation 68 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400MHz, CD3OD) d 1.05 (3H, d), 2.54 (1H, m), 2.78. (5H, m), 3.48 (2H, s), 4.52 (1H, m), 4.66 (2H, s), 6.15 (1H, m), 6.25 (2H, s) , 7.00 (1H, m), 7.08 (2H, m), 7.18 (1H, m), 7.27 (1H, m), 7.38 (2H, m).

LRMS: m / z APCl 503 [M + H]. Example 46 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - indan-2- il-acetamide The title compound was prepared from the compound of preparation 69 using the method described for example 12 and isolated as a white foam. 1 H NMR (400MHz, CD3OD) d 1.05 (3H, d), 2.58 (1H, m), 2.78 (6H, m), 3.22 (2H, m), 3.45 (2H, s), 4.56 (2H, m), 6.15 (1H, m), 6.25 (2H, s) ), 7.00 (8H, m). LRMS: m / z APCl 461 [M + H +]. Fjfimpln 47? / - (2-Chloro-6-fluorobenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -propyl} - phenyl) -acetamide The title compound was prepared from the compound of preparation 70 using the method described for example 12 and isolated in shape of a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 05 (3 H, d), 2.54 (1 H, m), 2.71 (2 H, m), 2.83 (2 H, m), 3.48 (2 H) , s), 4.57 (3H, m), 6.15 (1 H, s), 6.25 (2H, s), 7.27 (7H, m). LRMS: m / z APCl 487 [M + H +], 485 [MH "] Example 49? / - (4-Chlorobenzyl) -2- (3- { 2- [2- (3,5-dihydroxy) phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 72 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400MHz, CD3OD) d 1.05 (3H, d), 2.58 (1H, m), 2.71 (2H, m), 2.83 (1H, m), 2.90 (1H, m), 3.48 (2H, s), 4.38 (2H, s), 4.57 (1H, m) , 6.16 (1H, s), 6.25 (2H, s), 7.02 (1H, d), 7.09 (1H, s), 7.11 (1H, m), 7.20 ( 3H, m), 7.28 (2H, m). LRMS: m / z APCl 469 [M + H +], 467 [M-H]. Fj mplo fi? / - (2,5-Dichloro-benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl -propyl.}. -phenyl) -acetamide The title compound was prepared from the compound of preparation 73 using the method described for example 12 and isolated as a white solid. 1 H NMR (400 MHz, CD 3 OD) d 1.12 (3 H, s), 1, 13 (3 H, s), 2.85 (4 H, m), 3.62 (2 H, s), 4.46 (2 H, s), 4.62 (1H, m), 6.23 (1H, m), 6.38 (2H, s), 7.20 (6H, m), 7.39 (1H, d). LRMS: m / z electrospray 517 [M + H +], 515 [MH "] Example 51? / - (3,5-Dichloro-benzyl) -2- (3- { 2- [2- (3, 5-dihydroxy-phenyl) -2-hydroxyl-ethylamino] -2-methyl-propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 74 using the method described for example 12 and isolated as a white solid. 1 H NMR (400MHz, CD3OD) d 1.11 (3H, s), 1.13 (3H, s), 2.85 (4H, m), 3.59 (2H, s), 4.37 (2H, s), 4.62 (1H, m), 6.23 (1H, m), 6.38 (2H, s), 7, 01 (1H, m), 7.12 (1H, m), 7.17 (3H, m), 7.28 (1H, d), 7.32 (1H, m). LRMS: m / z electrospray 517 [M + H +], 515 [MH "] Example 52? / - (2,6-Dichloro-benzyl) -2- (3- { 2- [2- (3, 5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 75 using the method described for example 12 and isolated as a white solid. 1 H NMR (400MHz, CD 3 OD) d 1.10 (3H, s), 1, 11 (3H, s), 2.82 (4H, m), 3.54 (2H, s), 4.60 (1H, m), 4.71 (2H, s), 6.22 (1H, m), 6.38 (2H, s), 7.07 (1H, m), 7.18 (2H, m), 7, 26 (1H, m), 7.31 (1H, m), 7.43 (1H, s), 7.45 (1H, m). LRMS: m / z electrospray 520 [M + H +], 518 [MH "] Example 53? / - Biphenyl-2-ylmethyl-2- (3- { 2- [2- (3,5-dihydroxy) phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 76 using the method described for example 12 and isolated as a white solid. 1 H NMR (400MHz, CD30D) d 1, 14 (3H, s), 1, 15 (3H, s), 2.82 (2H, m), 2.93 (2H, m), 3.52 (2H, s), 4.32 (2H, s), 4.62 (1 H, m), 6.23 (1 H, m), 6.38 (2H, s), 7.11 (13H, m). LRMS: m / z electrospray 527 [M + H +], 525 [MH "] Example 54? / - (2-Chlorobenzyl) -2- (3- { 2- [2- (3,5-dihydroxy) phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 77 using the method described for example 12 and isolated as a white foam. _ 1 H NMR (400MHz, CD 3 OD) d 1, 05 (3H, d), 2.56 (1H, m), 2.80 (4H, m), 3.55 (2H, s), 4.45 (2H , s), 4.52 (1H, m), 6.14 (1H, m), 6.25 (2H, s), 7.19 (8H, m). LRMS: m / z APCl 469 [M + H +]. Example 55? / - (3-Methoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy- ethylamino] -propyl} phenyl) -acetamide The title compound was prepared from the compound of preparation 78 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400MHz, CDsOD) d 1, 05 (3H, d), 2.60 (5H, m), 3.51 (2H, s), 3.69 (3H, s), 4.32 (2H, s), 4.51 (1H, m), 6.15 (1H, m), 6.25 (2H, s), 6.75 (3H, m), 7.02 (1H, m), 7 , 21 (4H, m). LRMS: m / z APCl 465 [M + H +]. Example 56? / - (3-Trifluoromethylbenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) - acetamide The title compound was prepared from the compound of preparation 79 using the method described for Example 12 and isolated as a pale brown foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 05 (3 H, d), 2.57 (1 H, m), 2.66 (2 H, m), 2.80 (1 H, m), 2.90 (1 H , m), 3.55 (2H, s), 4.43 (2H, s), 4.51 (1H, m), 6.16 (1 H, m), 6.25 (2H, s), 7.03 (1H, m), 7.07 (1H, s), 7.14 (1H, m), 7.21 ( 1H, m), 7.47 (2H, m), 7.53 (2H, m). LRMS: m / z APCl 503 [M + H +], 501 [MH "] Example 57? / - (3,4-Difluorobenzyl) -2- (3- { 2- [2- (3,5- dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 80 using the method described for Example 12 and isolated as a pale brown foam. 1 H NMR (400 MHz, CD 3 OD) d 1.05 (3 H, d), 2.58 (1 H, m), 2.66 (2 H, m), 2.80 (1 H, m), 2.90 (1 H , m), 3.53 (2H, s), 4.30 (2H, s), 4.52 (1H, m), 6.16 (1H, m), 6.24 (2H, s), 7 , 01 (2H, m), 7.15 (5H, m). LRMS: m / z APCl 471 [M + H +], 469 [MH "] Example 58? / - (2-Methoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy) phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 81 using the method described for Example 12 and isolated as a pale brown foam. 1 H NMR (400MHz, CD 3 OD) d 1.05 (3H, d), 2.57 (1H, m), 2.68 (2H, m), 2.80 (1H, m), 2.87 (1H, m), 3.53 (2H, s), 3.78 (3H, s), 4.35 (2H, s), 4.52 (1H, m), 6.16 (1H, m), 6 , 23 (2H, s), 6.84 (1 H, m), 6.91 (1H, m), 7.01 (1 H, m), 7.07 (1H, s), 7.15 ( 2H, m), 7.21 (2H, m). LRMS: m / z APCl 465 [M + H +], 463 [MH "] Example 59? / - (3,4-Dimethylbenzyl) -2- (3- { 2- [2- (3,5- dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 82 using the method described for example 12 and isolated as a pale brown foam. 1 H NMR (400MHz, CD 3 OD) d 1, 04 (3H, d), 2.19 (3H, s), 2.19 (3H, s), 2.57 (1H, m), 2.66 (2H, m), 2.78 (1H, m), 2.88 (1H, m), 3.49 (2H, s), 4.26 (2H, s), 4.49 (1H, m), 6 , 16 (1H, m), 6.24 (2H, s), 6.93 (1H, m), 6.97 (1H, s), 7.01 (2H, m), 7.06 (1H, s), 7.13 (1H, m), 7.19 (1H, m). LRMS: m / z APCl 463 [M + H +], 461 [M-H "].

Fjfimplo 60? - (3,4-Dimethoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) - Acetamida The title compound was prepared from the compound of Preparation 83 using the method described for Example 12 and isolated as a pale brown foam. 1 H NMR (400 MHz, CD 3 OD) d 1.04 (3 H, d), 2.57 (1 H, m), 2.66 (2 H, m), 2.79 (1 H, m), 2.88 (1 H , m), 3.50 (2H, s), 3.72 (3H, s), 3.78 (3H, s), 4.28 (2H, s), 4.50 (1H, m), 6 , 16 (1H, m), 6.24 (2H, s), 6.78 (2H, m), 6.85 (1H, m), 7.01 (1H, m), 7.07 (1H , s), 7.14 (1H, m), 7.19 (1H, m). LRMS: m / z APCl 495 [M + H +], 493 [MH "] Example 61? / - (2-Ethoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy) phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 84 using the method described for example 12 and isolated as a pale brown foam. 1 H NMR (400MHz, CD 3 OD) d 1.04 (3H, d), 1.35 (3H, t), 2.57 (1H, m), 2.68 (2H, m), 2.80 (1H, m), 2.88 (1H, m), 3.53 (2H, s), 4.00 (2H, c), 4.36 (2H, s), 4.50 (1H, m), 6, 15 (1H, m), 6.25 (2H, s), 6.83 (1H, m), 6.88 (1H, m), 7.01 (1H, m), 7.07 (1H, s) ), 7.15 (2H, m), 7.19 (2H, m). LRMS: m / z APCl 479 [M + H +], 477 [MH "]. Example 62? / - [2- (2-Chloro-phenyl) -ethyl] -2- (3-. {2- 2- [2 - (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 85 using the method described for example 12 and isolated as a pale brown foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 06 (3 H, d), 2.58 (1 H, m), 2.67 (2 H, m), 2.81 (1 H, m), 2.88 (3 H, m), 3.43 (4H, m), 4.53 (1H, m), 6.16 (1H, m), 6.24 (2H, s), 7.04 (3H, m), 7, 20 (6H, m). LRMS: m / z APCl 483 [M + H *], 481 [M-H "].

Example 63 4-. { [2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetylamino] -methyl} -benzamide The title compound was prepared from the compound of Preparation 86 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1.04 (3 H, d), 2.57 (1 H, m), 2.68 (2 H, m), 2.80 (1 H, m), 2.87 (1 H , m), 3.58 (2H, s), 4.38 (2H, s), 4.51 (1H, m), 6.17 (1H, m), 6.25 (2H, s), 7 , 01 (1H, d), 7.07 (2H, m), 7.20 (1H, m), 7.29 (2H, d), 7.80 (2H, d). LRMS: m / z APCl 478 [M + H +], 476 [MH "] Example 64 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.}. -phenyl) -? / - indan-1-yl-acetamide The title compound was prepared from the compound of preparation 87 using the method described for example 12 and isolated as a pale brown foam. H NMR (400MHz, CD3OD) d 1.05 (3H, d), 1.81 (1H, m), 2.46 (1H, m), 2.57 (1H, m), 2.72 (2H , m), 2.87 (4H, m), 3.52 (2H, m), 4.53 OH, m), 5.36 (1H, m), 6.16 (1H, m), 6 , 25 (2H, s), 7.01 (1H, m), 7.14 (7H, m). LRMS: m / z APCl 461 [M + H *], 459 [M-H1. Example 65 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (3-Fluoro-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of preparation 94 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400MHz, CD3OD) d 1.06 (3H, d), 2.80 (7H, m), 3.59 (2H, m), 4.55 (1H, m), 6.15 (1H , m), 6.26 (2H, s), 7.01 (3H, m), 7.30 (3H, m), 7.58 (2H, m). LRMS: m / z APCl 453 [M + H +].

Example 66 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2-Chloro-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of preparation 95 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 05 (3 H, d), 2.81 (5 H, m), 3.07 (2 H, t), 3.63 (2 H, t), 4.53 (1 H , m), 6.15 (1 H, m), 6.26 (2H, s), 7.20 (6H, m), 7.55 (2H, m). LRMS: m / z APCl 469 [M + H +]. EXAMPLE 67 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) - V -naphthalene-1-methylmethyl-acetamide The title compound was prepared from the compound of preparation 96 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400MHz, CD3OD) d 0.98 (3H, d), 2.47 (1H, m), 2.54 (2H, m), 2.78 (2H, m), 3.54 (2H, s), 4.51 (1H, m), 4.80 (2H, s), 6.17 (1H, s), 6.25 (2H, s), 6.98 (2H, m), 7, 07 (2H, m), 7.40 (4H, m), 7.78 (1H, d), 7.84 (1H, d), 7.90 (1H, d). LRMS: m / z APCl 485 [M + H +], 483 [MH "]. Example 68 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.}. -phenyl) - / V- (2-fluoro-5-trifluoromethyl-benzyl) -acetamide The title compound was prepared from the compound of preparation 97 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1.03 (3H, d), 2.47 (1H, m), 2.63 (2H, m), 2.78 (1H, m), 2.89 (1H, m), 3.54 (2H, s), 4.46 (2H, s), 4.58 (1H, m), 6.17 (1H, s), 6.22 (2H, s), 7, 01 (1H, d), 7.08 (2H, m), 7.20 (2H, m), 7.58 (2H, m). LRMS: m / z APCl 521 [M + H +], 519 [M-H].

Example 69 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.}. -phenyl) -? / - (3-chlorobenzyl) -i "" - »tam¡ria The title compound was prepared from the compound of preparation 98 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1.03 (3 H, d), 2.58 (1 H, m), 2.63 (2 H, m), 2.78 (1 H, m), 2.85 (1 H , m), 3.57 (2H, s), 4.38 (2H, s), 4.52 (1H, m), 6.17 (1H, s), 6.26 (2H, s), 7 , 01 (1H, d), 7.08 (1H, s), 7.20 (6H, m). LRMS: m / z APCl 469 [M + H +], 467 [MH "] Example 70 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.}. -phenyl) -? / - (4-fluoro-3-trifluoromethyl-benzyl) -acetamide The title compound was prepared from the compound of preparation 99 using the method described for example 12 and isolated in shape of a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1.03 (3 H, d), 2.58 (1 H, m), 2.63 (2 H, m), 2.78 (1 H, m), 2.89 (1 H, m), 3.52 (2H, s), 4.38 (2H, s), 4.52 (1H, m), 6.17 (1 H, s), 6.26 (2H, s) , 7.03 (1H, d), 7.08 (2H, m), 7.20 (2H, m), 7.51 (2H, m). LRMS: m / z APCl 521 [M + H +], 519 [MH "]. Example 71 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamide no] -2-methyl-propyl.}. -phenyl) -? / - (2-methylsulfanyl-benzyl) -acetamide The title compound was prepared from the compound of preparation 100 using the method described for example 12 and isolated as a white solid. 1 H NMR (400MHz, CD3OD) d 1.11 (3H, s), 1.12 (3H, s), 2.48 (3H, s), 2.85 (4H, m), 3.59 (2H, s), 4.47 (2H, s), 4.61 (1H, m), 6.23 (1H, m), 6.38 (2H, s), 7.07 (2H, m), 7, 26 (6H, m). LRMS: m / z electrospray 497 [M + H +], 494 [MH "]. Example 72 4- { [2- (3- { 2- [2- (3,5-D-hydroxy-phenyl ) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -acetylamino] -methyl.}. -benzamide The title compound was prepared from the compound of preparation 101 using the method described for example 12 and isolated as a white solid. 1 H NMR (400MHz, CD3OD) d 1.11 (3H, s), 1.12 (3H, s), 2.85 (4H, m), 3.60 (2H, s), 4.46 (2H, s), 4.61 (1H, m), 6.23 (1H, m), 6.38 (2H, s), 7.10 (1H, d), 7.22 (2H, m), 7, 28 (1H, m), 7.34 (2H, d), 7.82 (2H, d). LRMS: m / z electrospray 493 [M + H + J, 491 [MH "]. EXAMPLE 73 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino ] -2-methyl-propyl.}. -phenyl) -? / - (4-sulfamoyl-benzyl) -acetamide The title compound was prepared from the compound of preparation 102 using the method described for example 12 and isolated as a white solid. 1 H NMR (400 MHz, CD 3 OD) d 1, 12 (3 H, s), 1, 13 (3 H, s), 2.85 (4 H, m), 3.60 (2 H, s), 4.47 (2 H, s), 4.61 (1H, m), 6.23 (1H, m), 6.38 (2H, s), 7.10 (1 H, d), 7.22 (2H, m), 7.28 (1H, m), 7.40 (2H, d), 7.84 (2H, d). LRMS: m / z electrospray 529 [M + H +], 527 [MH "] Example 74. 4- [{[2- (3- { 2- [2- (3,5-dihydroxy)] methyl ester -phenyl) -2-hydroxy-ethylamino] -2-methylpropyl.} - phenyl) -acetylamino] -methyl.} - benzoic acid The title compound was prepared from the compound of Preparation 103 using the method described for Example 12 and isolated as a white solid. 1 H NMR (400MHz, CD 3 OD) d 1.08 (3H, s), 1, 10 (3H, s), 2.85 (4H, m), 3.60 (2H, s), 3.92 (3H, s), 4.47 (2H, s), 4.61 (1H, m), 6.22 (1H, m), 6.38 (2H, s), 7.09 (1H, d), 7.20 (2H, m), 7.28 (1 H, m), 7.37 (2H, d), 7.95 (2H, d). LRMS: m / z electrospray 508 [M + H +], 506 [MH "]. Example 75? / - (1-Benzyl-piperidin-4-yl) -2- (3- { 2- [2- ( 3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -acetamide The title compound was prepared from the compound of preparation 104 using the method described for example 12 and isolated as a white solid. 1 H NMR (400 MHz, CD 3 OD) d 1, 12 (3 H, s), 1, 13 (3 H, s), 1.55 (2 H, m), 1.87 (2 H, m), 2.15 (2 H, m), 2.80 (6H, m), 3.50 (2H, s), 3.55 (2H, s), 3.68 (1H, m), 4.61 (1H, m), 6 , 22 (1 H, m), 6.37 (2 H, s), 7.08 (1 H, d), 7.18 (2 H, m), 7.26 (2 H, m), 7.35 ( 2H, s), 7.36 (2H, s). LRMS: m / z electrospray 533 [M + H +], 531 [MH "] Example 76 3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2-phenethyl] -benzamide The title compound was prepared from the compound of preparation 105 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1.06 (3 H, d), 2.62 (1 H, m), 2.75 (1 H, m), 2.80 (2 H, m), 2.94 (3 H , m), 3.58 (2H, t), 4.56 (1H, m), 6.16 (1H, m), 6.27 (2H, s), 7.18 (1H, m), 7 , 26 (6H, m), 7.57 (1H, s), 7.59 (1H, m). LRMS: m / z APCl 435 [M + H +], 433 [M-H "].

Example 77 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (5-fluoro-2-methyl-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of preparation 106 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 06 (3 H, d), 2.33 (3 H, s), 2.62 (1 H, m), 2.76 (1 H, m), 2.80 (2 H, m), '2.94 (3H, m), 3.58 (2H, t), 4.55 (1H, m), 6.17 (1H, m), 6.26 (2H, s), 6 , 82 (1H, m), 6.93 (1H, m), 7.12 (1H, m), 7.35 (2H, m), 7.57 (1 H, s), 7.61 (1 H, m). LRMS: m / z APCl 467 [M + H +], 465 [MH "]. Example 78 3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? ('- [2- (2-trifluoromethyl-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of preparation 107 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 06 (3 H, d), 2.62 (1 H, m), 2.75 (1 H, m), 2.82 (2 H, m), 2.98 ( 1 H, m), 3.12 (2H, t), 3.62 (2H, t), 4.56 (1H, m), 6.17 (1 H, m), 6.26 (2H, s) ), 7.35 (3H, m), 7.50 (2H, m), 7.61 (3H, m). LRMS: m / z APCl 503 [M + H +], 501 [MH "] Example 79 3- {2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - (2-naphthalen-1-yl-ethyl) -benzamide The title compound was prepared from the compound of preparation 108 using the method described for example 12 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1, 05 (3H, d), 2.60 (1H, m), 2.75 (3H, m), 2.96 (1H, m), 3.40 (2H , t), 3.70 (2H, t), 4.57 (1H, m), 6.17 (1H, m), 6.28 (2H, s), 7.35 (5H, m), 7.48 (3H, m), 7.59 (1H, m), 7.75 (1H, m), 7.84 (1H, m), 8.23 (1H, m). LRMS: m / z APCl 485 [M + H +], 483 [M-H "].

Example fifi 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2,4,5-Trimethyl-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of preparation 109 using the method described for example 12 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 05 (3 H, d), 2.17 (3 H, s), 2.17 (6 H, s), 2.27 (3 H, s), 2.62 (1 H, m), 2.75 (1H, m), 2.81 (4H, m), 2.98 (1H, m), 3.50 (2H, t), 4.55 (1H, m), 6, 17 (1 H, m), 6.26 (2H, s), 6.88 (1 H, s), 6.91 (1 H, s), 7.35 (2H, m), 10 7.38 (1 H, s), 7.40 (1 H, m). LRMS: m / z APCl 477 [M + H +], 475 [MH "] .Example 81 3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2,3-dimethyl-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of preparation 110 using the method described for Example 12 and isolated in shape of a white foam. 1 H NMR (400MHz, CD 3 OD) d 1, 05 (3H, d), 2.26 (3H, s), 2.26 (3H, s), 2.62 (1H, m), 2.75 (1H, m), 2.81 (2H, m), 2.95 (3H, m), 3.54 (2H, t), 4.56 (1H, m), 6.17 (1H, m), 6, 26 (2H, s), 6.98 (3H, m), 7.35 (2H, m), 7.38 (1H, s), 7.41 (1H, m). LRMS: m / z APCl 463 [M + H +], 461 [MH "] .Example 82 3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -prop L.} -? V- [2- (2-hydroxy-3-chloro-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of preparation 111 using the method described for example 12 and isolated as a white foam. 1 H NMR (400MHz, CD3OD) d 1.06 (3H, d), 2.62 (1H, m), 2.75. (1 H, m), 2.81 (2H, m), 2.95 (3H, m), 3.60 (2H, t), 4.56 (1H, m), 6.17 (1H, m ), 6.26 (2H, s), 6.74 (1H, m), 7.06 (1H, m), 7.17 (1H, m), 7.35 (2H, m), 7.57 ( 1H, s), 7.60 (1H, m). LRMS: m / z APCl 485 [M + H +], 483 [MH "] .Example 83 3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (4- chloro-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of preparation 112 using the method described for example 12 and isolated as a white foam. 1 H NMR (400MHz, CDsOD) d 1, 05 (3H, d), 2.62 (1H, m), 2.75 (1 H, m), 2.81 (2H, m), 2.95 (3H , m), 3.58 (2H, t), 4.56 (1 H, m), 6.17 (1H, m), 6.26 (2H, s), 7.30 (6H, m), 7.58 (2H, m). LRMS: m / z APCl 469 [M + H +], 467 [MH "] Example 84 3- {2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2-hydroxy-5-chloro-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of preparation 113 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 06 (3 H, d), 2.63 (1 H, m), 2.77 (1 H, m), 2.86 (4 H, m), 3.00 (1 H, m), 3.58 (2H, t), 4.57 (1 H, m), 6.17 (1H, m), 6.26 (2H, s), 10 6.78 (1H, m), 7.00 (1H, m), 7.09 (1H, m), 7.30 (2H, m), 7, 57 (1 H, s), 7.59 (1H, m). LRMS: m / z APCl 485 [M + H +], 483 [M-H. Example 85 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2-Chloro-4-fluoro-phenyl) -ethyl] -benzamide The title compound was prepared from the compound of preparation 114 using the method described for Example 12 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1.05 (3 H, d), 2.62 (1 H, m), 2.75 (1 H, m), 2.83 (2 H, m), 3.00 (1 H , m), 3.05 (2H, t), 3.62 (2H, t), 4.56 (1H, m), 6.17 (1H, m), 6.26 (2H, s), 6 , 99 (1H, m), 7.19 (1H, m), 7.35 (3H, m), 7.60 (2H, m). LRMS: m / z APCl 487 [M + H +], 485 [MH "] Example 86 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.}. -phenyl) -? / - (2-methyl-benzyl) -acetamide The title compound was prepared from the compound of preparation 115 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 04 (3 H, s), 1, 05 (3 H, s), 2.22 (3 H, s), 2.73 (3 H, m), 2.83 (1 H , m), 3.56 (2H, s), 4.37 (2H, s), 4.55 (1 H, m), 6.18 (1 H, m), 6.36 (2H, s) , 7.04 (1 H, d), 7.10 (6H, m), 7.21 (1 H, t). LRMS: m / z electrospray 465 [M + H +], 462 [MH "]. Example 87 2- (3- { 2- [2- (3,5-D-hydroxy-phenyl) -2-hydroxy- ethylamino] -2-methyl-propyl.}. -phenyl) - V- (3-methyl-benzyl) -acetamide The title compound was prepared from the compound of preparation 116 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 04 (3 H, s), 1, 05 (3 H, s), 2.23 (3 H, s), 2.73 (3 H, m), 2.83 (1 H , m), 3.56 (2H, s), 4.31 (2H, s), 4.55 (1H, m), 6.18 (1H, m), 6.36 (2H, s) , 7.04 (4H, m), 7.15 (3H, m), 7.21 (1H, t). LRMS: m / z electrospray 465 [M + H +], 462 [MH "] Example 88 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (4-methyl-benzyl) -acetamide The title compound was prepared from the compound of preparation 117 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1.04 (3H, s), 1, 05 (3H, s), 2.27 (3H, s), 2.73 (3H, m), 2.83 (1H, m), 3.56 (2H, s), 4.28 (2H, s), 4.55 (1 H, m), 6.18 (1 H, m), 6.36 10 (2H, s) , 7.04 (1H, d), 7.10 (5H, m), 7.17 (1H, d), 7.22 (1H, m). LRMS: m / z electrospray 465 [M + H +], 462 [MH "J Example 89 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] - 2-methyl-propyl.}. -phenyl) -? / - (2-methoxy-benzyl) -acetamide The title compound was prepared from the compound of preparation 118 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1.04 (3H, s), 1.05 (3H, s), 2.68 (2H, t), 2.77 (1H, m), 2.83 (1H, m), 3.56 (2H, s), 3.79 (3H, s), 4.37 (2H, s), 4.55 (1 H, m), 6.18 (1H, m), 6.37 (2H, s), 6.82 (1H, m), 6.92 (1H, d), 7.03 (1H, d) ), 7.12 (3H, m), 7.22 (2H, m). LRMS: m / z electrospray 480 [M + H +], 478 [MH "]. Example 90 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-eti lamino] -2-methyl-propyl.}. -phenyl) -? / - (4-methoxy-benzyl) -acetamide The title compound was prepared from the compound of preparation 119 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1.04 (3H, s), 1, 05 (3H, s), 2.68 (3H, m), 2.83 (1H, m), 3.56 (2H, s), 3.77 (3H, s), 4.27 (2H, s), 4.55 (1H, m), 6.18 (1H, m), 6.36 (2H, s), 6, 92 (2H, d), 7.04 (2H, d), 7.17 (4H, m), 7.21 (1H, m). LRMS: m / z electrospray 481 [M + H +], 478 [MH "] Example 91 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.}. -phenyl) - / V- (2,3-dimethyl-benzyl) -acetamide The title compound was prepared from the compound of preparation 120 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 04 (3 H, s), 1, 05 (3 H, s), 2.15 (3 H, s), 2.24 (3 H, s), 2.68 (3 H, m), 2.83 (1H, m), 3.53 (2H, s), 4.37 (2H, s), 4.55 (1H, m), 6.18 (1H, m), 6 , 36 (2H, s), 7.02 (1H, d), 7.08 (3H, m), 7.11 (1H, m), 7.17 (1H, d), 7.21 (1H, m). LRMS: m / z electrospray 478 [M + H +], 476 [MH "]. Example 92 2- (3- { 2- [2- (3,5-D-hydroxy-phenyl) -2-hydroxy- ethylamino] -2-methyl-propyl.}. -phenyl) - / V- (3,4-dimethyl-benzyl) -acetamide The title compound was prepared from the compound of preparation 121 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1.04 (3H, s), 1.05 (3H, s), 2.19 (3H, s), 2.19 (3H, s), 2.68 (3H, m), 2.83 (1H, m), 3.54 (2H, s), 4.27 (2H, s), 4.55 (1H, m), 6.18 10 (1H, m), 6.36 (2H, s), 6.96 (1H, d), 6.97 (1H, s), 7.06 (2H, m), 7.11 (1H, m), 7.18 (1H, m), 7.21 (1H, m). LRMS: m / z electrospray 477 [M + H +], 475 [M-H.

Example 93 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (2- chloro-6-methyl-benzyl) -acetamide The title compound was prepared from the compound of preparation 122 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 04 (3 H, s), 1.05 (3 H, s), 2.37 (3 H, s), 2.68 (3 H, m), 2.83 (1 H, m), 3.47 (2H, s), 4.53 (2H, s), 4.55 (1H, m), 6.18 (1H, m), 6.36 (2H, s), 7, 04 (1H, d), 7.09 (1H, m), 7.18 (4H, m), 7.21 (1H, m). LRMS: m / z electrospray 497 [M + H +]. Example 94 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (3- chloro-4-methyl-benzyl) -acetamide The title compound was prepared from the compound of Preparation 123 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400 MHz, CD 3 OD) d 1, 04 (3 H, s), 1.05 (3 H, s), 2.31 (3 H, s), 2.68 (3 H, m), 2.83 (1 H, m), 3.56 (2H, s), 4.28 (2H, s), 4.53 (1H, m), 6.18 (1H, m), 6.36 (2H, s), 7 , 04 (1 H, d), 7.11 (1H, s), 7.18 (1 H, m), 7.21 (4H, m). LRMS: m / z electrospray 497 [M + H +]. EXAMPLE 95 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] -2-methylpropyl.} Phenyl) -? / - [2- (6-methoxynaphthalene-2- il) ethyl] acetamide The title compound was prepared from the compound of preparation 124 using the method described for Example 34 and isolated as a white foam. 1 H NMR (400MHz, CD 3 OD) d 1, 07 (3H, s), 1.07 (3H, s), 2.63 (2H, m), 2.81 (2H, m), 3.44 (2H, s), 3.51 (2H, m), 3.64 (2H, s), 3.87 (3H, s), 4.58 (1H, m), 6.18 (1H, m), 6.36 (2H, s), 7.04 (6H, m), 7.24 (1H, d), 7.47 (1H, s), 7.63 (2H, m). LRMS: m / z electrospray 543 [M + H +]. Example 96? / - (2-Chlorobenzyl) -3- (3- {2- [2- (3,5-dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) propionamide Prepared according to the procedure used for example 12, using preparation 142. 1 H NMR (400MHz, CD3OD) d 1, 04 (3H, d), 2.50-2.72 (3H, m), 2.65-2.75 (2H, m), 2.76-2.85 (1H, m), 2.86-2.95 (3H, m), 4.40 (2H, s), 4 53 (1 H, m), 6.16 (1H, m), 6.26 (2H, s), 6.94-7.08 (4H, m), 7.13-7.24 (3H, m) 7.35 (1 H, m); LRMS APCl m / z 483 [M + H] + Example 97? / - (2,6-Dichlorobenzyl) -3- (3- { 2- [2- (3,5-dihydroxyphenyl) -2-hydroxyethyla- mino] propyl.}. phenyl) propionamide Prepared according to the procedure used for example 12, using preparation 143. 1 H NMR (400MHz, CD3OD) d: 1, 04 (3H, d), 2.42-2.58 (3H, m), 2, 62-2.75 (2H, m), 2.76-2.95 (4H, m), 4.53 (1H, m), 4.62 (2H, s), 6.16 (1H, m), 6.25 (2H, s), 6.92 (1 H, m), 6.96 (1 H, s), 7.01 (1H, m), 7.13 (1 H, t) , 7.26 (1 H, t), 7.38 (2H, m); LRMS APCl m / z 517 [M + H +] Example 98 1- (3,4-Dihydro-1H-isoquinolin-2-yl) -3- (3- { 2- [2- (3,5-d.hydroxyphenyl) -2-hydroxyethylamino] propyl. phenyl) propan-1-one Prepared according to the procedure used for example 12, using preparation 144. 1 H NMR (400MHz, CD3OD) d: 1.03 (3H, d), 2.65-2.95 (11H, m) "3 , 62-3.75 (2H, m), 4.46-4.68 (3H, m), 6.16 (1H, m), 6.24 (2H, s), 6.84-7.19 (8H, m); LRMS APCl m / z 475 [M + H] + Example 99? / - (2-Chloro-4-fluorobenzyl) -2- (3- { 2- [2- (3,5-dihydroxyphenyl) -2- hydroxyethylamino] propyl.} phenyl) acetamide The title compound was prepared from the compound of preparation 145 using the method described for example 34. 1 H NMR (400MHz, CD3OD) d 1.00 (3H, d), 2.60-2.65 (1H, m), 2.64-2.68 (2H, m), 2.83-2.93 (1H, m), 3.48 (2H, s), 4.86 (2H, s), 4.47 -4.50 (1H, m), 6.11 (1H, s), 6.21 (2H, m), 6.99-7.83 (7H, m).

LRMS: m / z APCl 687 [M + H]. Example mn? / - (4-Bromobenzyl) -2- (3- {2- [2- (3,5-dihydroxyphenyl) -2-hydroxyethylamino] -2-methylpropyl} phenyl) acetamide The title compound was prepared from the compound of preparation 146 using the method described for Example 34. 1 H NMR (400MHz, CD3OD) d: 1, 07 (d, 6H), 2.63-2.78 (m , 3H), 2.84 (t, 1H), 3.57 5 (s, 2H), 4.31 (s, 2H), 4.53-4.57 (m, 1H), 6.18 (s) , 1H), 6.37 (s, 2H), 7.05 (d, 1H), 7.16 (t, 4H), 7.22 (t, 1H), 7.42 (d, 2H); LRMS APCl m / z 529 [M + H] +. Example 101 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] -2-methylpropyl.} Phenyl) -? / - (3,4-dimethylphenyl) acetamide The title compound was prepared from the compound of preparation 147 using the method described for example 34. 1 H NMR (400MHz, CD3OD) d: 1, 05 (d, 6H), 2.22 (d, 6H), 2,66- 2.78 (m, 3H), 2.83 (t, 1H), 3.62 (s, 2H), 4.56-4.59 (m, 1 H), 6.18 (s, 1 H) , 6.32 (s, 2H), 7.04 (t, 2H), 7.18-7.24 (m, 4H), 7.31 (s, 1H); LRMS APCl m / z 463 [M + H] +. Example 102 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) - / V- (2,3-dimethylbenzyl) acetamide The title compound was prepared from the compound of preparation 148 using the method described for example 12. 1 H NMR (400MHz, CD3OD) d: 0.99 (3H, s), 2.20 (3H, s), 2.48 (1H, dd), 2.61-2.67 (2H, m), 2.72 (1H, dd), 2.80 (1H, dt), 3.45 (2H, s), 4 , 31 (2H, s), 4.44 (1H, dd), 6.09 (1 H, t), 6.19 (1 H, s), 6.20 (1H, s), 6.92- 7.17 (7H, m); LRMS APCl m / z 462 [M + H] +. EXAMPLE 103 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) -? / - (4-fluorobenz-acetamide) The title compound was prepared from the compound of Preparation 149 using the method described for example 12. 1 H NMR (400MHz, CD 3 OD) d: 0.99 (3H, d), 2.49 (1H, dd), 2.60-2.66 (2H, m) , 2.74 (1H, dd), 2.82-2.89 (1 H, m), 3.46 (2H, s), 4.27 (2H, s), 4.46 (1 H, dd ), 6.12 (1H, t), 6.21 (1H, s), 6.22 (1 H, s), 6.91-6.98 (3H, m), 7.02-7.07 (2H, m), 7.03-7.21 (3H, m); LRMS APCl m / z 451 [M + H] +. Example 104 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) -1- (4-pyridin-2-ylpiperazin-1-yl) ethanone The title compound was prepared from the compound of preparation 150 using the method described for example 12. 1 H NMR (400MHz, CD3OD) d: 1.05 (3H, d), 2.59 (1H, dd), 2.78-2.93 (3H, m), 3.08-3.15 (1H, m), 3.31 (2H, t), 3.41 (2H, t), 3.59 (2H, t), 3.66 (2H, t), 3.77 (2H, s), 4.55 (1H, dd), 6.13 (1H, t), 6.25 (1H, s), 6, 26 (1 H, s), 6.62-6.65 (1 H, m), 6.73 (1 H, d), 7.02-7.11 (3H, m), 7.20 (1 H, t), 7.48 (1H, dt), 8.01 (1H, da); LRMS APCl m / z 491 [M + H] +. Example 105 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] -2-methylpropyl.} Phenyl) -? / - (2-phenylpropyl) acetamide The title compound was prepared from the compound of preparation 151 using the method described for example 12. 1 H NMR (400MHZ, CD3OD) d: 0.92 (3H, D), 1, 06 (3H, D), 2.40 (1H, DD), 2.53-2.59 (2H, M), 2.66 (1H, DD), 2.74-2.83 (2H, M), 3.14-3.24 (2H , M), 3.27 (2H, S), 4.38 (1H, DD), 6.02 (1H, T), 6.13 (1H, S), 6.13 (1H, S), 6, 83-6.90 (2H, M), 6.98-20.07 (4H, M), 7.08-7.13 92H, M); LRMS APCl M / Z 463 [M + Hf. The ability of the compounds of formula (1) to act as potent β2 agonists thereby mediating smooth muscle relaxation can be determined by measuring the effect of beta 2 -adrenergic receptor stimulation on contraction of stimulated guinea pig trachea strips by electric field. COBAYA TRACHEAL Male Dunkin-Hartley guinea pigs (475-525 g) are sacrificed by asphyxiation with CO2, exsanguinated through the femoral artery and the trachea is isolated. Four preparations are obtained from each animal, starting the dissection immediately below the larynx and taking 2.5 cm in length from the trachea. The trachea piece is opened by cutting the cartilage opposite the trachealis muscle, and then cross sections are cut with a width of 3-4 rings of cartilage. The resultant strip preparations are suspended in 5 ml organ baths using cotton threads tied through the upper and lower cartilage bands. The strips are equilibrated, de-stressed for 20 minutes in a modified Krebs Ringer's buffer (Sigma K0507) containing 3 μM Indometacin (Sigma 17378), 10 μM Guanetidin (Sigma G8520) and 10 μM Atenolol (Sigma A7655), heated to 37 ° C and gasified with 95% 02/5% CO2, before applying an initial tension of 1 g. The preparations are allowed to equilibrate for an additional 30-45 minutes, during which time they are re-tensed (up to 1 g) twice at 15 minute intervals. Changes in voltage are recorded and controlled by conventional isometric transducers coupled to a data collection system (custom designed in Pfizer). After equilibration of tension, the tissues are subjected to electric field stimulation (EFS) using the following parameters: series of 10 s every 2 minutes, pulse width 0.1 ms, 10 Hz and maximum voltage (25 volts) continuously to throughout the whole experiment. The SAI of postganglionic cholinergic nerves in the trachea produces monophasic smooth muscle contractions and contraction height is recorded. Organ baths are constantly perfused with the Krebs Ringer buffer described above by means of a peristaltic pump system (pump flow rate 7.5 ml / minute) throughout the experiment, with the exception of when added a beta-2 agonist according to the present invention, then the pump is stopped during the time of the cumulative dosing to the bath and starts again after reaching a maximum response for the washing period. EXPERIMENTAL PROTOCOL TO EVALUATE THE POWER AND EFFICACY After equilibration to the SAI, the peristaltic pump is stopped and the preparations are "primed" with a single dose of 300 nM isoprenaline (Sigma 15627) to establish a maximum response in terms of inhibition of the contractile response to EFS. The isoprenaline is then removed by washing for a period of 40 minutes. After priming and recovery of the wash, a standard curve for isoprenaline is made in all tissues (Isoprenaline Curve 1) by means of the cumulative addition of a bolus to the bath using semilogarithmic increases in concentration. The concentration range used is 1e "9 a 1e / 3e" 6 M. At the end of the isoprenaline curve, the preparations are washed again for 40 minutes before starting a second curve, either for isoprenaline (as internal control) or a beta-2 agonist according to the present invention. Responses to the beta-2 agonist are expressed as inhibition as a percentage of the response to EFS. The data for the beta-2 agonist are normalized by expressing the inhibition as a percentage of the maximal inhibition induced by soprenaline in Curve 1. The CE value for the beta-2 agonist according to the present invention refers to the concentration of the compound required to produce the semi-maximal effect. Data for agonists Beta-2 according to the present invention are then expressed as relative potency with respect to isoprenaline defined by the ratio (Beta-2 agonist CE) / (EC50 of Isoprenaline). CONFIRMATION OF FUNCTIONAL ACTIVITY MEASURED BY BETA-2 The beta-2 agonist activity of the test compounds is confirmed using the above protocol, however, before constructing the curve for the β2 agonist according to the present invention, the preparations are pre-incubate (for a minimum of 45 minutes) with IC1 118551 300 nM (a selective β2 antagonist) which, in the case of a beta-2 mediated effect, causes a shift to the right of the dose response curve of test compound. According to another alternative, the agonist potency for the β2 receptor of the compounds of the formula (1) can also be determined by measuring the concentration of compound according to the present invention required to produce a semi-maximum effect (CEso) for the receptor ß2. PREPARATION OF COMPOUND A 10 mM stock solution / DMSO (dimethylsulfoxide) is diluted 100% up to the higher dose required in 4% DMSO. This higher dose is used to construct a semilogarithmic dilution curve of 10 points, all in 4% DMSO. Isoprenaline (Sigma, I-5627) was used as control in each experiment and for the control wells in each plate. The data is expressed as% response to Isoprenaline. CELL CULTURE CHO cells (Chinese hamster ovary) recombinantly expressing the human β2 adrenergic receptor (from Kobilka et al., PNAS 84: 46-50, 1987 and Bouvier et al., Mol Pharmacol 33: 133-) were cultured. 139 1988 CHOhß2) in MEM / NUT MIX F12 from Dulbecco (Gibco, 21331-020) supplemented with 10% fetal bovine serum (Sigma, F4135, Lot 90K8404 Exp 09/04), 2 mM glutamine (Sigma, G7513), geneticin 500 μg / ml (Sigma, G7034) and 10 μg / ml puromycin (Sigma, P8833). Cells were seeded to provide approximately 90% confluency for the assay. TEST METHOD 25 μl / well of each dose of compound were transferred to a cAMP-Flashplate® (NEN, SMP004B) with 1% DMSO as baseline controls and 100 nM Isoprenaline as maximum controls. This was diluted 1: 2 by the addition of 25 μl / well of PBS. The cells were trypsinized (0.25% of Sigma, T4049), were washed with PBS (Gibco, 14040-174) and resuspended in stimulation buffer (NEN, SMP004B) to give 1x106 cells / ml of CHOhB2. The compounds were incubated with 50 μl / well of cells for 1 hour. The cells were then used by the addition of 100 μl / well of detection buffer (NEN, SMP004B) containing 0.18 μCi / ml of 125 I-cAMP (NEN, NEX-130) and the plates were incubated at room temperature for 2 more hours The amount of 125l-cAMP bound to the Flashplate® is quantified using a Topcount NXT (Packard), with normal counting efficiency for 1 minute. The dose-response data were expressed as% Isoprenaline activity and adjusted using a four-parameter sigmoid fit. Thus, it has been found that the compounds of formula (1) according to the present invention illustrated in examples 1 to 105 above show a cAMP of β2 less than 30 nM.

Claims (6)

CLAIMS 1.- U compound of general formula (1): wherein the group (CH2) n-C (= O) Q is in the meta position or for, -R1 and R2 are independently selected from H and alkyl C1-C4, -n is 0, 1 or 2 and -Q1 is a group selected from, * -NR8-Q2-A or * -NR8-Q3, where -pes1 or2yges1 or2, -Q is a single bond or a C1-C4 alkylene optionally substituted with OH, - R is H or C1-C4 alkyl and, - Q or phenoxy, - A is selected from: C3-C10 cycloalkyl, said cycloalkyl optionally being linked with one or more, preferably 1, 2, 3 or 4, carbon atoms, and optionally being substituted with a hydroxy group, 5-6 membered heterocyclic group, optionally aromatic, containing one or two heteroatoms selected from O, N or S, optionally substituted with one or two substituents selected from C 1 -C 4 alkyl, benzyl and cyclopropylmethyl or a group quinolyl or isoquinolyl. - R3, R4, R5, R6 and R7 are the same or different and are selected from H, C1-C4 alkyl, OR9, SR9, SOR9, SO2R9, halo, CN, CF3, OCF3, SO2NR9R10, COOR9, CONR9R10, NR9R10, NHCOR10 and phenyl optionally substituted with OH; 9 10 -R and R are the same or different and are selected from H or C 1 -C 4 alkyl, - R 11 is selected from H or OH, and, - R 12 and R 13 are the same or different and are selected from H, C 1 -C 4 alkyl optionally substituted with OR 9, OR 9, C (= O) NH 2, C ( = O) CH3, N (CH3) C (= O) CH3, C (= O) OR9, phenyl optionally substituted with halogen, pyridyl optionally substituted with CN, oxadiazolyl optionally substituted with C1-C4 alkyl, and, - * represents the point of attachment to the carbonyl group; or, if appropriate, its pharmaceutically acceptable salts and / or isomers, tautomers, solvates or isotopic variations thereof. 2. A compound of general formula (1) according to claim 1, wherein the group (CH2) nC (= O) Q1 is in the meta position or para, -R1 and R2 are independently selected from H and C1-C4 alkyl, -n is 0, 1 or 2 and -Q1 is a group selected from, and a group * -NR8-Q2-A, where p is 1 or 2, Q2 is a Ci-C4 alkylene, R8 is H or C1-C4 alkyl and A is pyridyl, C3-C10 cycloalkyl, said cycloalkyl being optionally linked with 1, 2, 3 or 4 carbon atoms, tetrahydropyranyl, piperidinyl, tetrahydrothiopyranyl or a group - R3, R4, R5, R6 and R7 are the same or different and are selected from H, C1-C4 alkyl, OR9, SR9, SOR9, SO2R9, halo, CN, CF3, OCF3, SO NR9R10, COOR9, CONR9R10, NR9R10, NHCOR10 and phenyl optionally substituted by OH, 9 -R and R are the same or different and are selected from H or C? -C alkyl and represents the point of attachment to the carbonyl group; or, if appropriate, its pharmaceutically acceptable salts and / or isomers, tautomers, solvates or isotopic variations thereof. 3. A compound according to claim 1 or 2, wherein Q1 is a group * -NH-Q2-A, where A is cyclohexyl or adamantyl. 4. A compound according to claim 1 or 2 wherein A is naphthyl optionally substituted with OR9. 5. A compound according to claim 2, wherein Q1 is a group * -NH-Q2-A, where A is a group where R3, R4, R5, R6 and R7 are the same or different and are selected from H, C1-C4 alkyl, OR9, SR9, halo, CN, CF3, OCF3, SO2NR9R10, COOR9, CONR9R10, NR9R10, NHCOR10 and optionally substituted phenyl with OH, with the proviso that at least 2 of R3 to R7 are H; Wherein R and R are the same or different and are selected from H or C 1 -C 4 alkyl. 6. A compound according to any of Claims 1 to 5 wherein Q2 is -CH2-, - (CH2) 2-, - (CH2) 3-, -CH (CH3) -, -CH2CH (CH3) - or C (CH3) 2-. 7. A compound according to claim 1 or 2 in the where R3, R4, Rs and Re are H. 8. A compound according to any of claims 1 to 7 wherein R1 is H or CH3 and R2 is CH3. 9. A compound according to any of claims 1 to 8 wherein n is 0 or 1. 10. The stereoisomer (R, R) of a compound according to any one of claims 1 to 9. 11- A compound according to any one of 5 claims 1 to 10 in which the group (CH2) nC (= O) Q1 is in the meta position. 12. A compound according to claim 1 selected from the group consisting of:? / - benzyl-2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-me-o-tylpropyl) phenyl] acetamide; ? / - cyclopropyl-2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropy) phenyl] -N - [(1fi, 2S) -2- (hydroxymethyl) cyclohexyl] acetamide; 5- 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (3-morpholin-4-ylpropyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (pyridin-2-ylmethyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) or phenyl] -? / - (2-morpholin-4) -lethyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - isopropylacetamide; ? / - (4-chlorobenzyl) -2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3) 5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - [2- (dimethylamino) ethyl] acetamide; - [2- (diethylamino) ethyl] -2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [3- (dimethylamino) propyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] - / -pentylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (2-pyrrolidin-1-ylethyl) acetamide; ? / - (2,4-dichlorobenzyl) -2- [3- (2 { [2- (3,5-dihydroxy-phenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] acetamide; ? / - (3,4-dichlorobenzyl) -2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (4-methoxybenzyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (2- hydroxyethyl) acetamide; 2- [3- (2- { [2- (3,5-D-Hydroxyphenyl) -2-hydroxyethyl] amino} -2-methy1propyl) phenyl] -? / - propylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2- (methylpropyl) phenyl] -? / - (3-methoxypropyl) acetamide; / -cyclobutyl-2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} - 2-methylpropyl) phenyl] acetamide; 2- 2- [3 - (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1) -1- (1-naphthyl) ) ethyl] acetamide;? / - 2,3-dihydro-1H-inden-1-yl-2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2- hydroxy) useful] amino] -2-methylpropyl) phenyl] acetamide, 2- [3- (2- {[[(3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) or phenyl] -? / - [2- (1-methylpyrrolidin-2-yl) ethyl] acetamide; 2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino .) -2-) methylpropyl) phenyl] -? / - (4-fluorobenzyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (4-phenylbutyl) acetamide; 2- 2- [3- (2- { [2- (3,5-d, Hydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (3-methoxybenzyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxy-phenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (3-ethoxypropyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) or phenyl] -? / - (3,4,5-trimethoxybenzyl) acetamide; 2- [3- (2- { [2- (3,5-D-Hydroxy-phenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - [4- (trifluoromethyl) ) benzyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [2- (trifluoromethyl) benzyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (3,5-dimethoxybenzyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (2-phenoxyethyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 S) -2-hydroxy -1-methyl ethyl ketamine; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 S) -1 - ( hydroxymethyl) -2-methylpropyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 S, 2S) -1 - (hydroxymethyl) -2-methylbutyl] acetamide; ? / - [(1R) -1-Benzyl-2-hydroxyethyl] -2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2- methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 R) -1 - ( hydroxymethyl) propyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 S) -1 - ( hydroxymethyl) -2,2-dimethylpropyl] acetamide; ? / - [(1S) -2-cyclohexyl-1- (hydroxymethyl) ethyl] -2- [3- (2 { [2- (3,5-dihydro-xyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 S, 2f?) - 2-hydroxy-2,3-dihydro-1 V-inden-1-yl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (2-propoxyethyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (4-hydroxycyclohexyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (3-propoxypropyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - ethyl -? / - (2-hydroxyethyl) acetamide; 1-. { [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetyl} piperidine-4-carboxamide; 5-. { 2 - [(2- {3- [2- (4-acetyl-piperazin-1-yl) -2-oxoethyl] phenyl} -1, 1-dimethylethyl) amino] -1-hydroxyethyl} benzene-1, 3-diol; 5-. { 2 - [(2- {3- [2- (3,4-dihydroisoquinolin-2 (1 /) -yl) -2-oxoethyl] phenyl} -1,1-dimethylethyl) amino] -1- hydroxyethyl} benzene-1, 3-diol; ? / - benzyl-2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - methylacetamide; 5- (1-hydroxy-2- { [2- (3- { 2- [4- (2-Hydroxyethyl) piperazin-1-yl] -2-oxoethyl} phenyl) -1, 1-dimethylethyl] amino.} Ethyl) benzene-1,3-diol; 5- (2- { [2- (3- { 2- [4- (4-chlorophenyl) -4-hydroxypiperidin-1-yl] -2-oxoethyl}. Phenyl) -1, 1- dimethylethyl] amino.} -1-hydroxyethyl) benzene-1,3-diol; 5-. { 2 - [(1,1-dimethyl-2- { 3- [2- (4-methyl-piperazin-1-yl) -2-oxo-ethyl] -phenyl} -ethyl) -amino] -1-hydroxyethyl} benzene-1,3-diol; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - methyl -? / - (2-phenylethyl) acetamide; 5-. { 2 - [(1,1-Dimethyl-2-. {3- [2-oxo-2- (4-pyridin-2-ylpiperazin-1-yl) ethyl] phenyl] ethyl) amino] -1- hydroxyethyl} benzene-1, 3-diol; 2- 2- [3- (2- { [2- (3,5-dihydroxy-phenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - [3- (dimethylamino) propyl] -? / - methylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (2-hydroxyethyl) - / V- propylacetamide; ? / - [2- (diethylamino) ethyl] -2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl-1-yl] -amino} -2-methylpropyl ) phenyl] -? / - methylacetamide; 5-. { 2 - [(1,1-dimethyl-2- { 3- [2- (4-methyl-1,4-diazepan-1-yl) -2-oxoethyl] phenyl} ethyl) amino] -1-Hydroxyethyl} benzene-1, 3-diol; 5- [2- ( { 1, 1-dimethyl-2- [3- (2-morpholin-4-yl-2-oxoethyl) phenyl] ethyl} amino) -1-hydroxyethyl] benzene-1, 3-diol; 2- 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - methyl -? / - [(1 S) -1-phenylethyl] acetamide; 5- [2- ( { 1, 1-dimethyl-2- [3- (2-oxo-2-piperidin-1-ylethyl) phenyl] ethyl} amino) -1-hydroxyethyl) benzene-1, 3-diol; 5- (1-hydroxy-2- { [2- (3 { 2 - [(3f?) - 3-hydroxypyrrolidin-1-yl] -2-oxoethyl}. Phenyl) 0 -1, 1-dimethylethyl] amino.} Ethyl) benzene-1,3-diol; 5- (1-hydroxy-2- { [2- (3- {2 - [(3f?) - 3-hydroxypiperidin-1-yl] -2-oxoethyl}. Phenyl) -1 , 1-dimethylethyl] amino.} Ethyl) benzene-1,3-diol; 5-. { 2 - [(2- {3- [2- (4-acetyl-1,4-diazepan-1-yl) -2-oxoethyl] phenyl} -1,1-dimethylethyl) amino] -1- hydroxyethyl} benzene-1, 3-diol; 5- (1-hydroxy-2- { [2- (3- { 2- [4- (hydroxymethyl) piperidin-1-yl] -2-oxoethyl}. Phenyl) -1,1-dimethylethyl. ] amino.} ethyl) benzene-1,3-diol; ? / - (1- {[[3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpro-pyl) phenyl] acetyl}. pyrrolidin-3-yl) -? / - methylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (2-methoxyethyl) - / V- propylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - ethyl -? / - (2 -methoxyethyl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) pheny] -? / - [3- (dimethylamino) - 2,2-dimethylpropyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [3-fluoro-5- (tr Fluoromethyl) benzyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - [(1 S) -1 - ( hydroxymethyl) -3-methylbutyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] - / V - [(1 S) -2-hydrox -1-phenylethyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -N, / V-diethylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - 1 H -pyrazol-5-ylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (5-methyl-1H- pyrazol-3-yl) acetamide; ? / - (cyclohexylmethyl) -2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetamide; 4-. { [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetyl} ethyl piperazin-1-carboxylate; ? / - (5-Chloropyridin-2-yl) -2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (6-methylpyridin-2- il) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (3-methylpyridin-2-yl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - isoquinolin-1-ylacetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - (4,6-dimethylpyridin- 2-yl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (2-methoxybenzyl) acetamide; ? / - [(1S) -1-Benzyl-2-hydroxyethyl] -2- [3- (2 { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino]. 2-methylpropyl) phenyl] acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (1-ethyl-1 7-pyrazole -5-yl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] -? / - (1,3-dimethyl-1 H -pyrazol-5-yl) acetamide; 2- [3- (2- { [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl] amino.} -2-methylpropyl) phenyl] - / V- (3-fluorobenzyl) acetamide; 1-. { [3- (2-. {[[2- (3,5-dihydroxy-phenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] acetyl} -L-prolinamide; 5-. { 2 - [(2- {3- [2- (5-amino-3-tert-butyl-1H-pyrazol-1-yl) -2-oxoethyl] phenyl} -1, 1- (methylethyl) amino] -1-hydroxyethyl.} benzene-1,3-diol; 2- [3- (2 { [2- (3,5-d.hydroxyphenyl) -2-hydroxyethyl] amino} -2-methylpropyl) phenyl] -? / - [(1 S) -1-phenylethylketamide; 5- { 2 - [(2- { 3- [2- (1,4-dioxa-8- azapiro [4.5] dec-8-yl) -2-oxoethyl] phenyl] -1, 1-dimethylethyl) amino] -1-hydroxyethyl}. benzene-1,3-diol;? / - [2 - (4-Chloro-phenyl) -ethyl] -3-. {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -2-methyl-propyl} -benzamide; ? / - Adamantan-1 -yl-2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; 3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} -? / - [2- (3-fluoro-phenyl); -ethyl] -benzamide; / V- [2- (2-chloro-phenyl) -etl] -3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy "ethylamino ] -2-methyl-propyl.}. -benzamide; 3- {2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -N - [2- (2,3-dimethyl-phenyl) -ethyl] -benzamide; ? / - [2- (2-Chloro-4-fluoro-phenyl) -ethyl] -3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxyethylamino] -2-methyl-propyl} -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -? / - [2- (4-methoxy-2,3-dimethyl-phenyl) -ethyl] -benzamide; 5? / - (3,4-Dichloro-benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethyl) -2- methyl-propyl.}. phenyl) -acetamide; ? / - (3,4-Dichloro-benzyl) -3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -benzamide; / V- (4-Chloro-benzyl) -3-. { 2- [2- (3,5-D-Hydroxy-phenyl) -2-hydroxy-ethylami-O no] -2-methyl-propyl} -benzamide; ? / - Adamantan-1-il-3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -benzamide; ? / - (4-Chloro-benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamido] -2-methyl-propyl.} .phenyl) -acetamide; 5? / - (4-Trifluoromethoxybenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -2-methyl-propyl} -phenyl ) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - pyridin-2-yl -methyl-acetamide; ? / - (3,4-Dichloro-benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino} -propyl} -phenyl ) -acetamide; ? / - (Benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl] -phenyl) -acetamide; ? / - Cyclohexylmethyl-2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; 1- (3,4-Dihydro-1H-isoquinolin-2-yl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -propyl}. phenyl) -ethanone; 5? / - Benzyl-2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl] -phenyl) -? / - methyl -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - (2-hydroxy-benzyl) -acetamide; ? / - (4-Cyano-benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino) -2-methyl-propyl}-phenyl) -acetamide; ? / - (2,4-Dichloro-benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -2-methyl-propyl} .phenyl) -acetamide; ? / - (Benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methylpropyl.} - phenyl) -acetamide; 5? / - (2-Chlorobenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamido} -2-methyl-propyl}. phenyl) -acetamide; ? / - (3-Methoxybenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} - phenyl) -acetamide; ? / - (Cyclohexylmethyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylami-O no] -2-methyl-propyl.} - phenyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - phenethyl-acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (4-chlorophenethyl) -acetamide; 2- (3- { 2- [2- (3,5-D-Hydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} -phenyl) -? / - ( 4-phenylphenethyl) -acetamide; 2- (3- {2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl-N-^ -hydroxy -biphenyl-S-ilmethyl-acetamide;? / - Cycloheptyl-2- (3. {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl}-phenyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - or phenethyl-acetamide; 2- (3-. {2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - (2-methylsulfanyl- benzyl) -acetamide;? / - (2,6-Dichloro-benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl}-phenyl) -acetamide: 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - indan-2-yl-acetamide;? / - (2-Chloro-6-fluorobenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino ] -propyl.}.-phenyl] -acetamide;? / - (4-chlorobenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy- ethylami-or not] -propyl.}. -phenyl) -acetamide;? / - (2,5-Dichloro-benzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl ) -2-hydroxyethylamino] -2- methyl-propyl} phenyl) -acetamide; ? / - (3,5-Dichloro-benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino} -2-methyl-propyl} .phenyl) -acetamide; N- (2,6-Dichloro-benzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino} -2-methyl-propyl}. phenyl) -acetamide; ? / - Biphenyl-2-ylmethyl-2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -acetamide; ? / - (2-Chlorobenzyl) -2- (3- { 2- [2- (3,5-d.hydroxy-phenyl) -2-hydroxy-ethylamino] -propyl. .-phenyl) -acetamide; ? / - (3-Methoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; ? / - (3-Trifluoromethylbenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} - phenyl) -acetamide; ? / - (3,4-Difluorobenzyl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethyl-amino] -propyl} -phenyl) -acetamide; / V- (2-Methoxybenzyl) -2- (3- { 2- [2- (3,5-d.hydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; / V- (3,4-Dimethylbenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -propyl.} - phenyl) -acetamide; ? / - (3,4-Dimethoxybenzyl) -2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -acetamide; 4-. { [2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.}. -pheneyl) -acetylamino] -methyl} -benzamide; 2- (3- { 2- [2- (3,5-Dihydroxr-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - indan-1-yl-acetamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (3-fluorophenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2-chlorophenyl) -ethyl] -benzamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - naphthalen-1-ylmethyl-acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - (2-fluoro-5- trifluoromethyl-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - (3-chlorobenzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl.} - phenyl) -? / - (4-fluoro-3-trifluoromethyl- benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (2- methylsulfanyl-benzyl) -acetamide; 4-. { [2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl} -phenyl) -acetylamino] -methyl} -benzamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) - / V- (4-sulfamoyl- benzyl) -acetamide; Methyl ester of 4- acid. { [2- (3- { 2- [2- (3,5-dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -acetylamino] -methyl} -benzoic;
1. - (1-Benzyl-piperidin-4-yl) -2- (3- {2- [2- (3,5-dihydroxy-phenyl) -2-hydroxyethylamino] -2-methyl-propyl} .phenyl) -acetamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- phenethyl] -benzamide; 5- 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (5-fluoro-2-methyl-phenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -N- [2- (2-trifluoromethyl-phenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -N- (2-or naphthalen-1-ethyl-ethyl) -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} - / V- [2- (2,4,5-Trimethyl-phenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} - / V- [2- (2,3-dimethyl-phenyl) -ethyl] -benzamide; 5- 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2-hydroxy-3-chloro-phenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (4-chlorophenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -N- [2- (2-or hydroxy-5-chloro-phenyl) -ethyl] -benzamide; 3-. { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -propyl} -? / - [2- (2-chloro-4-fluoro-phenyl) -ethyl] -benzamide;
2. 2- (
3. 3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (2-methyl- benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (3-methyl- benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (
4. 4-methyl- benzyl) -acetamide; 2- (3- { 2- [2- (3,
5. 5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (2-methoxy) benzyl) -acetamide 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - ( 4-methoxy-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (2,3- dimethyl-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) - / V- (3,4- dimethyl-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) - / V- (2- chloro-
6. 6-methyl-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - (3-chloro- 4-methyl-benzyl) -acetamide; 2- (3- { 2- [2- (3,5-Dihydroxy-phenyl) -2-hydroxy-ethylamino] -2-methyl-propyl.} - phenyl) -? / - [2- (6 -methoxy-naphthalen-2-yl) -ethyl] -acetamide; ? / - (2-Chlorobenzyl) -3- (3- {2- [2- (3,5-dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) propionamide; ? / - (2,6-Dichlorobenzyl) -3- (3- {2- [2- (3,5-dihydroxyphenyl) -2-hydroxyethyl-amino] propyl} phenyl) propionamide; 1- (3,4-D yhydro-1H-isoquinolin-2-yl) -3- (3- {2- [2- (3,5-dihydroxyphenyl) -2-hydroxyethylamino] propyl}. phenyl) propan-1-one; 5? / - (2-Chloro-4-fluorobenzyl) -2- (3- {2- [2- (3,5-dihydroxyphenyl) -2-h -droxyethylamino] propyl} phenyl) acetamide; ? / - (4-Bromobenzyl) -2- (3- { 2- [2- (3,5-dihydroxyphenyl) -2-hydroxyethylamine] -2-methylpropyl.} Phenyl) acetamide; 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] -2-methylpropyl.] L O-phenyl) -? - (3,4-dimethylphenyl) acetamide; 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) -? / - (2,3-dimethylbenzyl) acetamide; 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) -? / - (4-fluorobenzyl) acetamide; 15 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] propyl} phenyl) -1 - (4-pyridin-2-ylpiperazin-1-yl) ethanone; and, 2- (3- { 2- [2- (3,5-Dihydroxyphenyl) -2-hydroxyethylamino] -2-methylpropyl}. phenyl) -? / - (2-phenylpropyl) acetamide 13. A pharmaceutical composition comprising at least 0 an effective amount of a compound of formula (1) as described in any one of claims 1 to 12 or a pharmaceutically acceptable salt or derivative form thereof. 14. A compound of the formula (1) as described in any one of claims 1 to 12 or a pharmaceutically acceptable salt, derivative form or composition thereof, for use as a medicament. 15. The use of a compound of formula (1) as described in any one of claims 1 to 12 or of a pharmaceutically acceptable salt, solvate or composition thereof, for the manufacture of a drug for the treatment of diseases , disorders and conditions selected from the group consisting of: 0 • asthma of any type, etiology or pathogenesis, in particular asthma that is a member selected from the group consisting of atopic asthma, non-atopic asthma, allergic asthma, bronchial-mediated atopic asthma IgE, bronchial asthma, essential asthma, true asthma, intrinsic asthma caused by pathophysiological alterations, extrinsic asthma 5 caused by environmental factors, essential asthma of unknown or unapparent origin, non-atopic asthma, bronchitic asthma, emphysematous asthma, asthma induced by exercise , asthma induced by allergens, asthma induced by cold air, occupational asthma, infectious asthma caused by infection by bacteria, fungi, protozoa or virus, non-allergic asthma, asthma or incipient, wheezing syndrome in children and bronchiolitis, • chronic or acute bronchoconstriction, chronic bronchitis, obstruction of the lower respiratory tract and emphysema, • obstructive or inflammatory diseases of the respiratory tract of any type, etiology or pathogenesis, in particular, an obstructive or inflammatory disease of the respiratory tract that is a member selected from the group consisting of chronic eosinophilic pneumonia, chronic obstructive pulmonary disease (COPD) ), COPD that includes chronic bronchitis, pulmonary emphysema or dyspnea associated or not associated with COPD, COPD characterized by irreversible and progressive airway obstruction, respiratory distress syndrome in adults (ARDS), exacerbation of posterior airway hyperreactivity to a therapy with other drugs and respiratory disease associated with pulmonary hypertension, • bronchitis of any kind, etiology or pathogenesis, in particular bronchitis which is a member selected from the group consisting of acute bronchitis, acute laryngotracheal bronchitis, arachidic bronchitis , bronchitis catarrhal, bronchitis with laryngotracheitis, dry bronchitis, infectious asthmatic bronchitis, productive bronchitis, bronchitis due to staphylococcus or streptococcus and gallbladder bronchitis, • acute lung injury, • bronchiectasis of any kind, etiology or pathogenesis, in particular bronchiectasis which is a selected member among the group composed of cylindrical bronchiectasis, bronchiectasis sacculate, fusiform bronchiectasis, capillary bronchiectasis, cystic bronchiectasis, bronchiectasis dry and follicular bronchiectasis. 16. A method of treating a mammal, including a human, with a β2-agonist, which includes treating said mammal with an effective amount of a compound of the formula (1) as described in any one of the claims. 1 to 12, or with a pharmaceutically acceptable salt, derivative form or composition thereof. 17.- Combination of a compound according to any one of claims 1 to 15 with other therapeutic agents selected from: (a) 5-lipoxygenase inhibitors (5-LO) or antagonists of the 5-lipoxygenase activation protein (FLAP), (b) Leukotriene antagonists (LTRA), including LTB4, LTC4, LTD4 and LTE4 antagonists, (c) Histamine receptor antagonists, including H1 and H3 antagonists, (d) Sympathomimetic vasoconstrictor agents, adrenoceptor agonists ai and 0: 2 for decongestant use, (e) M3 muscarinic receptor antagonists or anticholinergic agents, (f) PDE inhibitors, for example PDE3, PDE4 and PDE5 inhibitors, (g) Theophylline (h) Sodium cromoglycate(i) COX inhibitors, selective and nonselective inhibitors of COX-1 or COX-2 (NSAID) 0) Oral and inhaled glucocorticosteroids, such as DAGR (dissociated agonists of the corticoid receptor) (k) Monoclonal antibodies active against entities endogenous inflammatory agents, (I) Anti-tumor necrosis factor agents (anti-TNF-a) (m) Adhesion molecule inhibitors including VLA-4 (n) antagonists Quinine receptor antagonists Bi and B2 (o) Agents immunosuppressants, (p) matrix metalloprotease inhibitors (MMPs), (q) tachykinin receptor antagonists NK1, NK2 and NK3, (r) elastase inhibitors, (s) adenosine A2a receptor agonists, (t) inhibitors of Urokinase, (u) Compounds that act on dopamine receptors, for example D2 agonists, (v) Modulators of the NFkß pathway, for example inhibitors of IKK, (w) Modulators of cytokine signaling pathways such as an inhibitor of p38 MAP kinase, syk kinase or JAK kinase, (x) Agents that can be classified as mucolytic or antitussive, and (and) Antibiotics. .