MXPA01002132A - Aminoalcohol derivatives and their use as beta 3 adrenergic agonists - Google Patents

Abstract

This invention relates to new aminoalcohol derivatives or salts thereof represented by formula (I) wherein each symbol is as defined in the specification or salts thereof which have&bgr;3 adrenergic agonist activity and therefore have gut selective sympathomimetic, anti-ulcerous, anti-pancreatitis, lipolytic, anti-urinary incontinence and anti-pollakiuria activities, to processes for the preparation thereof, to a pharmaceutical composition comprising the same and to a method for the prevention and/or treatment of diseases indicated in the specification to a human being or an animal.

Description

DERIVATIVES OF AMINOALCOHOLES AND THEIR USE AS AGONISTS OF THE BETA 3 ADRENERGIC RECEIVER TECHNICAL FIELD This invention relates to new aminoalcohol derivatives and salts thereof, which are agonists of the β3 adrenergic receptor and useful as a medicine.

DISCLOSURE OF THE INVENTION This invention relates to novel derivatives of amiols or alcohols which are agonists of the β3 adrenergic receptor and the salts thereof. More in particular, it is related to: new aminoalcohol derivatives and their salts that exhibit selective non-selective activities of the intestines, such as roses, antipacreatitis, lipolytics, ani-incontinu urinary and anti-urinary frequency; with the processes for the preparation of the same; with a pharmaceutical composition comprising them; and with a method intended for the use of those cited, in a therapeutic manner, in the treatment and / or prevention of disorders. ga s t r o- in t e s t ina s 1 s caused by muscle contractions smooth, both in humans and animals. One of the objects of this invention is to provide new and useful aminoalcohol derivatives, as well as the salts thereof, which possess selective non-impairing activities of the intestines, an ti-u 1 roses, lipolytic, urinary and anti-urinary incontinence. Another object of this invention is to provide the processes for the preparation of said aminoalcohol derivatives and the salts of the same. Another object of this invention is to provide a pharmaceutical composition comprising, as an active ingredient, said aminoalcohol derivatives and salts thereof. Still another object of this invention is based on providing a therapeutic method for the treatment and / or prevention of the aforementioned diseases in humans or animals, through the use of said aminoalcohol derivatives and salts thereof .

The aminoalcohol derivatives which are the subject of this invention are new and can be represented by the following general formula [I]: wherein A is a heterocyclic or aryl group, each of which may have between 1 and 3 substituents - which may be the same or different - selected from a group consisting of halogen, hydroxy, amino, lower alkyl, 1 qui 1 - s ul f oni 1 ami not inferior, phenylalkoxy (in fe ri or), f eni 1 -al coxi carboni 1 amino (lower), -X- is a bond, -CH2-, -CH2-CH2-, -NH- - (CH,) n-CH = CH- (CH - - or - (CH.) UC C- (CI -U), "- (where CH2, -, -0-CH2-, -S-CH2-, -S-CH2-o-S02, -CH2-, lower alkoxy or acyloxy) and -0- cs -0- .S-, -SO-, -S0, -N-CO-, -CO-N-, R 10 R lll -Cl? -CO-N-, CH-CM. -N-, -SO N-, I and I 111 R10 R11 R10 pio -N-CO, -, -CO- or -N-, in which R 10 is hydrogen, or R IO R10 R1D lower alkyl, and R11 is inner alkyl, R6, R7, R8, and R9, each independently, are hydrogen, hydroxy, lower alkyl, lower alkenyl, lower alkoxy, lower alkoxy, and lower alkyl. lower) or aryl, which may have 1 to 3 lower alkoxy, n, myk, each independently, 0 to 6, pes 0 to 4, qes 1 to 4, and (linkages 0 6) R "is hydrogen a protective amino group, and R2, R3, R4 and R5, each independently, hydrogen, lower alkyl, lower alkylthio, lower alkyl sulfonyl, hydroxy, lower alkoxy, amino lower alkylamino, acylamino, N- (lower alkyl) -cylamino; carboxy; lower alkoxycarbonyl; carbamoyl, optionally substituted with one or two lower alkyl; hydroxy-lower alkyl; lower alkoxy-lower alkyl; acylamino-lower alkyl; N- (lower alkyl) -N- acylamino-lower alkyl; carboxy-lower alkyl; lower alkoxycarbonyl-lower alkyl; carbamoyl-lower alkyl, optionally substituted with one or two lower alkyl; or (wherein R12 and R13, each independently, is hydrogen or lower alkyl, or R12 and R13 can be linked to form a lower alkylene chain and j is 0 to 6). The compound [I] which is the subject of the present invention or a salt thereof can be prepared by the following processes. Step 1 or add salt from it Pro ce s or 2 or a salt of it [Ib] or a salt thereof where A, X, Y, Z, R1, R2, R3, R4 and R5, each of them are as previously described, and R1 is a protective amino group.

In the previous and subsequent description of this specification, the appropriate examples of the various definitions that should be included in the scope of the specification are explained. invention, in a detailed manner, as it is explained below. The term "lower" refers to a group having between 1 and 6 carbon atoms, unless otherwise specified. A suitable example of a "lower alkyl" or a part of "lower alkyl" may include straight or branched, having 1 to 6 carbon atoms, such as: methyl, ethyl, propyl, isopropyl, butyl, isobutyl , sec-butyl, tert-butyl, pentyl, 1-methyl pentyl, tert-pentyl, neo-pentyl, hexyl, isohexyl and the like. Suitable "lower alkenyl" may include: vinyl, l- (or 2-) propenyl, 1- (or 2- or 3-Jbutenyl, 1- (or 2- or 3- or 4-) pen t eni 1 o, l- (or 2- or 3- or 4- or 5-) hexenyl, methyl-vinyl, ethyl-vinyl, 1- (or 2- or 3-) me ti 1 - 1 - (or 2 -) pr open i 1 or, l- (or 2-or 3-) ethyl-1- (or 2 -) pr open i 1, l- (or 2- or 3- or 4-) methyl-l- (or 2- or 3-) butenyl, and the like, among which the preferred example may be C2-C4 alkenyl The "lower alkoxy" and the "lower alkoxy" portion may be straight or branched chain, such as: methoxy, ethoxy, propoxy, isopropoxy, 1-eti Ipr opoxy, butoxy, sec-butoxy, tert-butoxy, pentyloxy, neopentyloxy, t er-pen ti loxi, hexyloxy and the like, among which, the most preferred may be C alco-C alkoxy and the most preferred of all is methoxy. A suitable example of "halogen" can be fluo, chlorine, bromine and iodine. A suitable example of "aryl" and part "ar" may include: phenyl, naphthyl, anthryl and the like, among which phenyl may be preferred. A suitable example of "a heterocyclic group" can include an unsaturated heterocyclic group of 3 to 8 members (more preferably 5 or 6 members) containing 1 to 4 nitrogen atoms, for example: pyrrolyl, pyrrolinyl , imidazolyl, pyrazolyl, pyridyl, dihydric or dihydrogen, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl (for example, 4H-1, 2,4-triazolyl, 1 H-1, 2, 3-triazyl and 1 or, 2H-1,2,3-triazolyl, etc.), tetrazolyl (for example, 1H-tetrazolyl, 2H-tetrazolyl, etc.), etc .; a saturated heterocyclic group of 3 to 8 members (more preferably 5 or 6 members) containing from 1 to 4 nitrogen atoms, for example, pyrrolidinyl, imidazolidinyl, piperidyl, piperazinyl, etc.; An unsaturated, condensed heterocyclic group containing between 1 and 4 nitrogen atoms, for example: indolyl, isoindolyl, indolinyl, indole and zinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl benzotriazolyl, etc.; a 3 to 8 membered unsaturated mono- or clique group (more preferably 5 or 6 membered) containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, eg, oxazolyl , isoxazolyl, oxadiazolyl (for example, 1, 2, 4-oxadi azo 1 i 1 o, 1, 3, 4-oadiazo 1 i 1, 1,2,5-oxadiazolyl, etc.), etc.; a 3 to 8-membered saturated heterocyclic group (more preferably 5 or 6 membered) containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, eg, morpholinyl , Sidnonyl, etc .; an unsaturated condensed heterocyclic group containing from 1 to 2 oxygen atoms and from 1 to 3 nitrogen atoms, for example, benzoxazole, benzoxazole, etc. an unsaturated group of 3 to 8 membered monomers (most preferably 5 or 6 members) containing 1 to 2 sulfur atoms and between 1 and 3 nitrogen atoms, for example, thiazolyl, isothiazyl or thiadiazolyl (for example, 1,2,3-thiadiazolyl, 1, 2, 4-ti adi azyl or 1,3,4-thiadiazolyl, 1, 2 , 5-ti adi az ol i 1 o, etc.), dihydrothiazinyl, etc .; a saturated or saturated group of 3 to 8 members (more preferably 5 or 6 members) containing from 1 to 2 sulfur atoms and from 1 to 3 nitrogen atoms, for example, thiazo 1 i di ni 1 o, etc .; a hetero-unsaturated monocyclic group of 3 to 8 members (more preferably 5 or 6 members) containing 1 to 2 sulfur atoms, for example, thienyl, di i dr odi ti ini 1 o, dihydroditionil, etc .; a condensed or unsaturated, condensed group containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, for example, benzothiazolyl, benzothiadiazolyl, imidazothiadiazolyl, etc .; a group of three-to-eight-membered unsaturated monocyclic members (more preferably 5 or 6 members) containing an oxygen atom, for example, furyl, etc .; a saturated and saturated group of 3 to 8 members (most preferably 5 or 6 members) containing an oxygen atom, for example, tetrahydropyran, tetrahydropyran, etc.; a group has an unsaturated 3 to 8 membered cation (more preferably 5 or 6 membered) containing an oxygen atom and between 1 and 2 sulfur atoms, eg, dihydro-oxathiinyl , etc.; a heterocyclic group. unsaturated, condensed, containing an oxygen atom between 1 to 2 sulfur atoms, for example, ben z or t i in i 1 o, benzoditiinilo, etc.; an unsaturated, condensed heterocyclic group containing an oxygen atom and between 1 and 2 sulfur atoms, for example, benzoxathiinyl, etc.; 2-oxo-2, 3-dihydro-lH-benzimidazolyl; and imi lares. An appropriate example of a part of a "amino protecting group" can be a common protective amino group, such as acyl, eg, substituted or unsubstituted lower alkanoyl [eg, formyl, acetyl, propionyl, trifluoroacetyl, etc.], phthaloyl, alkoxycarbonyl lower [e.g., tert -toxycarbonyl, tert-ami-1-oxy-ca-rboni-1, etc.], for 1-substituted or unsubstituted or unsubstituted oxy-oxy [eg, benzyloxycarbonyl, p-nitrobenzyloxycarbonyl, etc. ], ar is 1 substituted or unsubstituted or substituted [eg, benzenesulphyl, tosyl, etc.], or tr of eni 1 - s ul f eni 1, ar-alkyl (lower) , [for example trityl, benzyl, etc.] and the like, wherein the preferred one is phenyl-lower alkyl such as benzyl. The "acyl" and the "acyl" portion can be esterified carboxy; carboxy; carbamoyl, optionally substituted with one or two lower alkyl; lower alkylsulfonyl [eg, me ti 1-su 1-f-onyl, eti-1; its 1-oni-1, propyl-sulfonyl-bute-1-sulphonyl, pentyl-1 -s-1 -s, hexyl-sulfonyl, etc.]; substituted or unsubstituted lower alkanoyl [eg, formyl] , acetyl, t rif 1 or acetyl, propanoyl, butanoyl, 2-methyl-1-yl, pentanoyl, 2,2-dimethyl-propanoyl, hexanoyl, etc.], and the like. 1 to 1 coxi-carboni 1 or lower substituted or unsubstituted [e.g., toxi-ca rboni lo, et ox i-ca rb oni 1, propoxi-ca rboni 1 o, bu t oxi ca rboni 1 o, Hexyloxy carbonyl, 2-ydoe t-oxycarbonyl, trifluoromyl-oxycarbonyl, 2, 2, 2-tri-chloro-oxo-rboni-1, etc.], 1-oxi-ca rbon i 1 substituted or unsubstituted [e.g., phenoxy-carboni 1 or, -no or phenoxy-ca boni 1 or, 2 -na fti 1 oxy-carboni 1 or, etc.], a r- a 1 coxica rboni 1 or (lower) substituted or unsubstituted [for example, benzyloxycarbonyl, phenethyloxycarbonyl, benzhydryloxycarbonyl, 4-nitrobenzyloxycarbonyl, etc.] and the like, among which the preferred may be a 1 coxycarbonyl 1 or lower and The most preferred of all can be ethoxycarbonyl. A suitable example of "lower alkyl sulpholamino" may include me til s ul f oni 1-amino, eti 1 su 1 f oni 1 - ami no, propylsulfonyl-amino, butylsulfonyl-amino, pen ti 1 s ul f oni 1 -amino, hexi 1 su 1 f oni 1 - ami no, and the like, where the favorite can be alquilsul fo ni lamino (C1-C4) and it can be the optimal one 1 - s ul f oni 1 ami no. A suitable example of "a heterocyclic group" in A may be referred to the previously mentioned "heterocyclic group", in which, the preferred one may be a heterocyclic, saturated, heterocyclic group. to 8 members (more preferably 5 or 6 members) containing 1 to 4 nitrogen atoms or an unsaturated, condensed heterocyclic group containing ~ 1 to 4 nitrogen atoms and the most preferred of all being pyridyl, indolyl or 2-oxo-2,3-dihydro-or-1 H-benzimidazolyl. The lower alkylene chain formed by R7 and R8 is a straight or branched chain alkylene, having between 1 and 6 carbon atoms and is exemplified by: methylene, ethylene, trimethylene, propylene, butylene, 1,2-dime ti 1 ethylene, pentamethylene and hexamethylene. Preferred embodiments of the compound [I] which is the subject of the present invention are as follows: A is pyridyl, indolyl, 2-oxo-2, 3 -di hi dr or -lH-benz imi da z ol i 1 oo phenyl, each of which may have between 1 and 3 substituents, the same or different, selected from a group consisting of: hydroxy, ami no - a 1 qu i 1 or lower (more preferably, methyl) , at 1 qu i 1 - its 1 f onil amino lower (more preferably, me t anis ul oni 1 ami), phenyl-lower alkoxy (more preferably, benzyloxy) and pheni 1 - to the coxy carboni 1 amino (lower (more preferably, benzyl 1 oxy-ca rbon i 1 amino), -X- is a bond, -CH2-, CH2-CH2-, -0-CH2 -o-S02-CH2-, - (in which R is hydrogen or hydroxy) and -Z- is (CH2) (CH2) n (where -Q- -OH-CG-N-o -CH-CH2-N-, where R is hydrogen or lower alkyl (more preferably, methyl) and R 11 is lower alkyl (more preferably, methyl), R6, R7, R8 and R9, each independently, is hydrogen, lower alkyl (more preferably, methyl) or aryl (with higher preference, phenyl), "which may have between 1 and 3 lower alkoxy (more preferably, methoxy), n, m and k, each independently, is 0 to 6, and r is 2 to 7) and (wherein i is 0 to 6), R1 is hydrogen or ar-lower alkyl (more preferably, benzyl), and R2, R3, R4 and R5, each independently, is hydrogen; lower alkyl (more preferably, methyl); lower alkylthio (more preferably, methylthio); lower alkylsulfonyl (more preferably, methanesulfonyl); hydroxy; lower alkoxy (more preferably, methoxy or ethoxy); Not me; lower alkylamino (more preferably, methylamino); acylamino (more preferably, lower alkoxycarbonylamino, at 1 qui 1 - s) ul oni 1 not lower amine, lower alkanoylamino, ureido otrif luo- ce tilamino, par excellence, I am given rboni 1 amino, ethoxycarbonylamino, me t an ul 1 oni ami, formylamino, acetylamino or propionylamino); N- (alkyl) inf e r i or) a ci 1 amino [with greater, preference tilia 1 qui 1 or lower) - [alkoxycarbonyl (in f er i or)] ami no, par excellence, N-me t i 1 -me toxi -carbonylamino]; carboxy; or lower alkoxycarbonyl (more preferably, I oxygenate rboni 1 o). The most preferred embodiments of the compound [I] which is the object of the present invention are as follows: A is phenyl, each of which may have between 1 and 3 substituents, the same or different ones , selected from a group consisting of hydroxy, amino, at 1 qui 1 - s ul ony 1 amino lower (more preferably, me ss ul ul ony 1 amy) and phenyl-alkoxy (lower) ( more preferably, benzyloxy), -X- is a bond -CH2-, CH2- CH2-, - 0- CH2-0-S02-CH2-, (in which R 11 is hydrogen hydroxy -z- is (CH2) n- (CH2. (where R6, R7, R8 and R9, each independently, is hydrogen, lower alkyl (more preferably, methyl) or phenyl, which may have between 1 and 3 lower alkoxy (more preferably, methoxy), n, m, and k, each independently, is 0 or 1). R1 is hydrogen or phenyl-lower alkyl (more preferably, benzyl), and R2, R3, R4 and R5, each independently, is hydrogen; lower alkyl (more preferably, methyl); lower alkylthio (more preferably, methylthio); interior alkyl sulfonyl (more preferably methane sulfonyl); hydroxy; lower alkoxy (more preferably, methoxy or ethoxy); Not me; lower alkylamino (more preferably, methylamino); lower alkoxycarbonylamino (more preferably, methoxy-carbonylamino or ethoxy-carbonylamino); at 1 qui 1 - s ul f oni 1 amino lower (more preferably, methansulfonylamino); lower alkanoylamino (more preferably, formylamino, acetylamino or propionylamino); ureido; trifluoroacetylamino; N - (alkyl n r r o r) - [a 1 cox i ca rb on i 1 (i n f er i or)] ami no (more preferably, N-methyl- methoxycarbonylamino); carboxy; or lower alkoxycarbonyl (more preferably, methoxycarbonyl). Suitable salts of the aminoalcohol derivatives which are the subject of the invention [I] are pharmaceutically acceptable salts and include: non-toxic salts with entionals, such as an addition salt of an inorganic acid [eg, hydrochloride, hydrobromide, sulfate, phosphate, etc.]; an addition salt of an organic acid [eg, formate, acetate, trifluoacetate, oxalate, maleate, fumarate, tartrate, me t an ss ul ph ona, benzenesulfonate, t oluen u ul on, etc.], a salt of alkali metals [eg, a sodium salt, a potassium salt, etc.] or the like. The processes intended for the preparation of the compound [I] which is the object of the present are explained in a detailed manner as it is explained below. P oces or 1 The compound [I] constituting the subject hereof, or a salt thereof, can be prepared by reacting a compound [II] with a compound, [III] or a salt thereof The suitable salt of the compound [III] may be the same as those exemplified for the compound [I]. The reaction is preferably carried out in the presence of a base, such as an alkali metal carbonate [eg, sodium carbonate, potassium carbonate, etc.], an alkaline earth metal carbonate [eg, magnesium carbonate] , calcium carbonate, etc.] a bicarbonate of alkali metals [eg, sodium bicarbonate, potassium bicarbonate, etc.], a tri-alkylamine (lower) [eg trimethylamine, triethylamine, etc.], picoline imi lares. Typically, the reaction is carried out in a conventional solvent, such as an alcohol [eg, methanol, ethanol, propanol, isopropanol, etc.], diethyl ether, tetrahydrofuran, dioxane or any other organic solvent that does not adversely influence the reaction. The reaction temperature is not critical and the reaction can be carried out in cold conditions until heated.

Process 2 The compound [Ib] which represents an object of the present invention or a salt thereof can be prepared by subjecting a compound [la] - or a salt thereof - to the reaction, eliminating the protective amino group. Suitable salts of the compounds [la] and [Ib] may be the same as those exemplified for the compound [I]. This reaction is carried out according to a conventional method such as hydrolysis, reduction or the like. The hydrolysis is preferably carried out in the presence of a base or acid, including Lewis acid. The suitable base may comprise an inorganic base and an organic base, such as an alkali metal [eg, sodium, potassium, etc.], an alkaline earth metal [eg, magnesium, calcium, etc.], hydroxide or carbonate or bicarbonate thereof, hydrazine, trialkylamine [eg, trimethylamine, triethylamine, etc.], picoline, 1,5-diazabicyclo [4.3.0] non-5-ene, 1,4-di az abi cyc 1 or [2.2. 2] oc t a, 1,8-di az abi cycle [5.4.0] unde c-7-ene, or the like.

The suitable acid may include an organic acid [eg formic acid, acetic acid, propionic acid, trichloroacetic acid, trifluoroacetic acid, etc.], an inorganic acid [e.g. hydrochloric acid, hydrobromic acid , sulfuric acid, hydrogen chloride, hydrogen bromide, hydrogen fluoride, -etc.] and a compound of the acid addition salt [for example pyridine hydrochloride, etc.]. The elimination employing trichloroacetic acid, trifluoroacetic acid, etc., or the like, is preferably carried out in the presence of cation capture agents [e.g., anisole, phenol, etc . ] The reaction is usually carried out in a solvent, such as water, an alcohol [eg, methanol, ethanol, etc.], methylene chloride, chloroform tetrachloride or tetrane, tetrahydrofuran, a mixture thereof. or any other solvent that does not adversely affect the reaction. It is also possible to use a base or a liquid acid as a solvent. The reaction temperature is not critical and the reaction It is usually carried out under cooling, until heated. The reduction method applicable for the elimination reaction may include chemical reduction and catalytic reduction. The reducing agents suitable for use in chemical reduction are a combination of metals [eg, tin, zinc, iron, etc.] or a metal compound [eg, chromium chloride, chromium acetate, etc.] and an acid organic or inorganic [eg, formic acid, acetic acid, propionic acid, trifluoric acid, p-toluenesulfonic acid, hydrochloric acid, hydrobromic acid, etc.]. Suitable catalysts to be used in catalytic reduction are the catalysts, such as: platinum catalysts [for example platinum plate, platinum sponge, platinum black, colloidal platinum, platinum oxide, platinum ambient etc. ]; palladium catalysts [for example palladium sponge, palladium black, palladium oxide, palladium on carbon, colloidal palladium, palladium on barium sulfate, palladium on barium carbonate etc.]; nickel catalysts [for example nickel reduced, nickel oxide, Raney nickel, etc.]; cobalt catalysts [eg reduced cobalt, Raney cobalt, etc.]; iron catalysts [eg reduced iron, Raney iron, etc.]; copper catalysts [eg, reduced copper, Raney copper, Ullman copper, etc.]; and similar. In the case where the amino protecting group is benzyl, the reduction is preferably carried out in the presence of a combination of palladium catalysts [for example palladium black, palladium on carbon, etc.] and formic acid or its salt [for example Ammonium, etc. ] The reduction is generally carried out in a solvent with entional, which does not adversely affect the reaction, such as water, an alcohol [eg, methanol, ethanol, propanol, etc.], chlorobenzene , N, N-dimethylformamide or a mixture thereof. Additionally, in the case where the aforementioned acids to be used in a chemical reduction are liquid, they can also be used as a solvent. On the other hand, a suitable solvent to be used in a catalytic reduction can be the solvent, mentioned above and other solvents with encionales, such as diethyl ether, dioxane, tetrahydrofuran, etc. or a mixture of them. The reaction temperature of this reduction is not critical and the reaction is generally carried out under cooling until heating. The compounds obtained in the processes mentioned above can be isolated and purified by a conventional method, such as pultrization, recrystallization, column chromatography, reprinting and the like, and converted to the desired salt, by putting into practice the conventional procedures, if necessary. It should be noted that the compound [I] and the other compounds can include one or more stereoisomers, due to the asymmetric carbon atoms and all said isomers, as well as a mixture thereof are included within the scope of this invention. It is further emphasized that the reorganization of the compound [I] which is the object of the present invention can be produced by the effect of the light acid, the base or the like and the compound obtained as a result of said effect.

Isomerization or reorganization is also included in the scope of the present invention. It is also emphasized that the solvating form of the compound [I] (eg, hydrate, etc.) and any crystal form of the compound [I] are included in the scope of the present invention. The compound [I] which is the subject of the present invention or a salt thereof possesses selective omimatic activities of the intestines, anti-u 1 waxy, an ti -pa ncreatitis, lipolytic and anti-pollakiuria and are useful in the treatment and / or in the prevention of disorders ga stro - in testi na 1 is caused by contractions of smooth muscle in both humans and animals and, more in particular, for methods intended for the treatment and / or prevention of: spasm or hyper ana cine sia in the case of irritable bowel syndrome, gastritis, gastric ulcers, duodenal ulcer, enteritis, col ecis t opa tia , cholangitis, urinary calculus and the like; for the treatment, and / or the prevention of ulcers, such as gastric ulcer, duodenal ulcer, peptic ulcer, causes of ulcer by anti-inflammatory calculations without steroids, or the like; for the treatment and / or prevention of dysuria, for example, urinary frequency, urinary incontinence or the like, in the case of urinary frequency, neurogenic bladder failure, nocturia, unstable bladder, cystitis, chronic cystitis, chronic prostatitis, prostatic hypertrophy or the like; and for the - treatment and / or prevention of pancreatitis, obesity, diabetes, glycosuria, h ip e r 1 ip i demi, hypertension, atherosclerosis, glaucoma, melancholia, depression or the like; and for the treatment and / or prevention of diseases, as a result of insulin resistance (e.g., hypertension, hyperinsulinemia, etc.), and the like. In order to show the usefulness of the compound [I] for the prophylactic or therapeutic treatment of the aforementioned diseases, both in humans and animals, the data of the pharmacological test of a representative compound thereof are presented in how much is explained below: Test Effect of the increase in intravesical pressure induced by carbachol in an anesthetized dog.

Test Compound (1) (2 S) -1 - [[(2 RS) 4, 4-bis (4-hydroxy-f-enyl) -2-butyl] amino] -3-phenoxy-2-p-rhopanol hydrochloride.

Test method Beagle bitches, whose weight fluctuated between 8.0 and 15.0 kg, were fasted for 24 hours and kept under halothane anesthesia. A Foley 12F catheter was lubricated with water-soluble jelly, inserted into the urethral orifice and progressed approximately 10 cm until the tip of the balloon was well placed inside the bladder. Then, the balloon was inflated with 5 ml of ambient air and the catheter withdrew slowly, barely past the first resistance felt in the neck of the bladder. The urine was drained completely through the catheter and 30 ml of biological saline solution was infused. The catheter was connected to a pressure transducer and the pressure intravesical was recorded continuously. The test compound was injected intravenously, 5 minutes before administration of carbachol (1.8 μg / kg).

Test results The Preparations and the Embodiments given below serve illustrative purposes of this invention.

Example 1 A sol u.c ion of (2S) -3-phenoxy-1, 2-epoxypropane (195 mg) (IL FÁRMACO, 50 (10), 643 (1995)) and 4, 4 -bi s (4-hydroxyfyl) -2-butylamine (257 mg) in ethanol (2 ml) was stirred under reflux for 24 hours and evaporated in vacuo. The residue it was subjected to chromatography (chloroform-methanol) on silica gel (9 g) and the eluate was treated with 4N hydrogen chloride, in ethyl acetate, to obtain a crude oil, which was pulverized from diethyl ether, to obtain (2S) -1 - [[(2RS) -4,4-bis (4-hydroxy-f-enyl) -2-butyl] -amino] -3-phenoxy-2-propanol (117 mg) hydrochloride, as a brown powder Clear. p. of f. : 73 ° C (dec.) IR (Nujol): 3600-3100, 2700-2400, 1230 cm "1 NMR (DMSO-d6, d): 1.21-1.27 (3H, m, CH3), 1.94 (1H, m, CH2), 2.60 (lH, m, CH2), 2.85- 3.2 (3H, m, CH2NCH), 3.95 (1H, m, CHAr2), 4.01-4.05 (2H, m, ArOCH2), 4.16 (lH, m, CHOH), 5, 85 (1H, br s, OH), 6.64-6.72 (4H, m, H Aromatic), 6.92-7.16 (7H, m, aromatic H), 7.26-7.35 ( 2H, m, aromatic H), 8.62 (1H, br, NH), 8.92 (1H, br, HCl), 9.23 (1H, br s, OH), 9.28 (1H, br s , OH) MS m / z: 408 (M + + l) EXAMPLE 2 The hydrochloride of (2R) -N-benzyl-4,4-bis (4-me t oxi f eni 1) -2-bu ti 1 amine (412 mg) was converted to the corresponding free base, from a usual way A solution of tin chloride (IV) 1.0M in dichloromethane (1.5 ml) was added dropwise to a stirred solution of the free base and (2S) -3-f-enoxy-1, 2-epoxypr opane (225 mg) (IL DRUG, 50 (10) , 643 (1995)) in dichloromethane (4 ml), at -10 / -5 ° C, under a nitrogen atmosphere, for 10 minutes and the resulting mixture was stirred for 1 minute., 5 hours, at the same temperature. The reaction mixture was poured into IN hydrochloric acid and the mixture was stirred under ice cooling for 20 minutes. The organic layer was separated, washed with an aqueous solution of sodium fluoride and a saturated aqueous solution of sodium bicarbonate, dried over sodium sulfate and evaporated in vacuo. The residue was subjected to chromatography (ethyl acetate) on silica gel (11 g) and the eluate was treated with 4N hydrogen chloride in ethyl acetate to obtain (2 S) -1 - [N-benzyl-] hydrochloride. [(2R) -4,4 -bi s (4-methoxyphenyl) -2-butyl] amino] -3-phenoxy-2-propanol (136 mg) as an oil. IR (Film): 3292, 2850-2400, 1243 cm "1 NMR (CDC13, d): 1.27 and 1.47 (3H, each d, J = 6.2 and 6, 6 Hz); 2.08 (1H, m), 2.9-3.5 (4H, m), 3.68-4.0 (2H, m), 3.74, 3.75 and 3.76 (6H, each s), 4.02-4.08 (2H, m), 4.10-4.26 (1H,), 4.3-4.6 (1Hm), 6.72-7.43 and 7.64-7 , 68 (18H, m) MS m / z: 526 (M ++ l).

EXAMPLE 3 The hydrochloride of (2 S) -N-Benz i 1-4,4-bis (4-me toxi phenyl) -2 -bu ti 1 amine (412 mg) was converted to the corresponding free base, in a manner Similary. A solution of the free base and (2S) -3-f-enoxy-1,2-epoxypropane (195 mg) (IL F RMACO, 50 (10), 643 (1995)) in ethanol (4 ml) was stirred under reflux for 10 hours, cooled to room temperature and evaporated in vacuo. The residue was subjected to chromatography (chloroform) on silica gel and the eluate was treated with 4N hydrogen chloride, in ethyl acetate, to obtain (2S) -1- [N-benzyl- [(2S) - hydrochloride] 4, 4 -bi s - (4-methoxyphenyl) -2-butyl] amino] -3-phenoxy-2-propanol (549 mg) as an amorphous powder. [a] 24: -22.59 ° (c = 0.54, MeOH) D: IR (KBr): 3300 (br), 2850-2400, 1248 c "1 NMR (CDC13, d): 1.41 and 1.56 (3H, each d, J = 6.6 Hz), 1.64 and 2.05 (1H, m), 2.94-3.6 (4H, m), 3.74, 3.75, 3 , 76 and 3.77 (6H, each s), 3.87-3.96 (2H, m), 4.05-4.25 (3H, m) 4.5-4.65 and 4.8 (1H, m), 5.9 (1H, br), 6, 69-6, 98 (8 H, m), 7.08-7.17 (4H, m), 7.22-7.41 (4H, m), 7.65-7.73 (2H, m). MS m / z: 526 (M + + l).

Example 4 A mixture of (2S) -1- [N-benzyl- [(2R) -4,4-bis (4-methoxyphenyl) -2-butyl] amino] -3-phenoxy-2-propanol hydrochloride (96 mg) and 10% Pd / C (50% humidity, 60 mg) in methanol (4 ml), was stirred at room temperature, in the presence of hydrogen, at atmospheric pressure, for 6 hours and filtered. The filtrate was evaporated in vacuo and the residue was partitioned between dichloromethane and an aqueous solution of sodium bicarbonate. The organic layer was separated, dried over sodium sulfate and evaporated in vacuo. The residue was subjected to chromatography (di c 1 or orne ta no -me t an o 1), on silica gel (2 g) to obtain an oil, which was converted into the corresponding oxalate, in a similar manner, to To obtain oxalate from (2S) -1 - [[(2 R) -4, -bi s (4-methoxyphenyl) -2-butyl] amino] -3-phenoxy-2-propanol (1: 1) ( 26 mg), as a colorless powder. p. of f: 121-123 ° C (of diethyl ether) IR (KBr): 3423 (br), 2850-2650, 1734, 1701, 1633, 1603, 1250 cm-1 NMR (DMSO-d6 d): 1.23 (3H, d, J = 6.3 Hz), 1.99 (1H, m), 2.58 (lH, m), 2.85-3.01 (2H, m), 3.11-3.17 (1H, m), 3.69 (3H, s), 3.71 (3H, s), 3.9-6.6 (8H,), 6.81-6.99 (7H, m), 7.16-7.35 (6H, m). MS m / z. : 436 (M + + l) EXAMPLE 5 The following compound was obtained according to a method similar to that used in Example 4. Oxalate of (2 S) -1 - [[(2 S) -4,4-B is (4 - methoxyphenyl) -2-butyl] amino] -3-phenoxy-2-propanol (1: 1) [a] 24: 11.06 ° (c = 0.515, MeOH) D p. f: 79-94 ° C (diethyl ether) IR (KBr): 3423 (br), 2750-2400, 1739-1691 (m), 1643, 1608, 1247 cm-1 NMR (DMSO-d6, d) : 1, 25 (3H, d, J = 6, 3 Hz), 1, 96 (1H, m) 2, 66 (1H, m) 2, 86 (1H, m) 2, 95-3, 15 (2H, m), 3, 69 (3H, s), 3, 70 (3H, s) 3, 94-4, 15 (4H,), 5, 1 (4H, br), 6, 81-6, 88 (4H, m), 6, 92-6, 99 (3H,), 7, 17-7, 35 (6H, m) MS m / z: 436 (M ++ l) Preparation 1 A mixture of methyl 3-aminobutane (4.3 g), (2S) -3-phenoxy-1, 2-epoxypropane (4.59 g), t ri f luome t an ul s The mixture of ytterbium (III) (1.8 g) and dichloromethane (25 ml) was stirred at 40 ° C, 2 hours at room temperature overnight, worked in the usual manner and purified by column chromatography on silica gel (toluene: ethanol: concentrated ammonia water = 9: 1: 0.1) to obtain acid methyl ester. (3RS) -3 - [((2S) -2-hydroxy-3-f enoxipr opi 1 o) ami no] bu tiri co (2.59 g). IR (Pure): 3400 (br m), 1734 (s), 1599 (m), 1495 (m), 1458 (1-0, 1298 (m), 1246 (s), 1041 (m), 756 (m) cm "1 NMR (CDC13, d): 1.16 (3H, d, J = 5.2 Hz), 2.41-2.46 (2H, m), 2.6-3.0 (2H, m) 5.14 (1H, quartet, J = 6.4 Hz), 3.68 (3H, s), 3.9-4.1 (3H, m), 6.90-6.99 (3H, m) 7.24-7.33 (2H, m) MS m / z: 268 (M + + 1) Preparation 2 A mixture of (2 S) -N-benzyl 1 - (2-h-dr ox i -3-phenoxy-propyl 1) amine (142 mg), ethyl ester of acid - . 5-b omope t ano co (173 mg), potassium carbonate, (153 mg) and N, N -dime ti 1 formamide (2 ml) was stirred at 80 ° C for 4.5 hours, worked in the usual manner and purified by column chromatography on silica gel (20%). ethyl acetate-hexane), in order to obtain (2S) -5- [N-benzyl- (2-hydroxy-3-phenoxy-p-op-i-o) amino] pentylane ethyl ester. (93 mg). NMR (CDC13, d): 1.25 (3H t, J = 7, l Hz), 1.5- 1.7 (5H, broad), 2.2-2.4 (2H, m), 2, 4-2.8 (4H, m), 3.5-3.7 (1H, m), 3.7-3.9 (1H, m), 3.94 (2H, t, J = 3.9 Hz) 4.0-4.2 (1H, m), 4.12 (2H, quartet, J = 7, 1 Hz), 6.86-6.98 (4H, m), 7 , 2-7.4 (6H, m). MS m / z: 386 (M + + 1) Preparation 3 The following compound was obtained according to a method similar to that used in Preparation 2. (2S) -4- [N-benzyl- (2-hydroxy-3-phenoxypropyl) amino] -methyl ester butanoic IR (Pure): 3482 (br m), 2949 (m), 1736 (s), 1599 (w), 1495 (m), 1456 (m), 1246 (s), 1041 (m), 754 (m) , 696 (m) cm_1 NMR (CDC13, d): 1.88 (2H, quintet, J = 7, l Hz), 2.32 (2H, t, J = 7.2 Hz), 2.5-2 , 8 (4H, m), 3.5-3.7 (1H, m), 3.64 (3H, s), 3.84 (1H, d, J = 13.0 Hz), 3.89- 4.0 (2H, m), 4.0-4.2 (1H, m), 6.86-6, 99 (4H, m), 7.2-7.4 (6H, m). MS m / z: 358 (M ++ l) Preparation 4 The following compounds were obtained in accordance with a method similar to that used in Example 6 (1) 1- [2.2-Bis (4-methoxyphenyl) -2-hydroxyethyl] cyclopentanol IR (KBr): 3347 (s), 3240 (m), 2958 (s), 1608 (m), 1510 (s), 1466 (m), 1248 (s), 117 (m), 1034 (s), 835 (m) cm "1 NMR (CDC13, d): 1.2-1.7 (8H, m), 9.39 (1H, br s), 2.70 (2H, s), 3.78 (6H, s), 4.87 (1H, br s), 6.82 (4H, d, J = 8, 9 Hz), 7.37 (4H, d, J = 8, 9 Hz). (2) 3- (Didecylamino) -1, 1-bis (4-bromophenyl) -1-propanol NMR (CDCl 3, d): 2.3-2.4 (2H, m), 2.6-2.7 (2H, m), 3.51 (4H, s), 7.07 (2H, d, J = 8.5), 7.1-7.4 (16 H, m) MS m / z: 564, 566 (M * + l), 568 (3) (3RS) -3- (Dibenzylamino) -1 , 1-bis (4-bromofenyl) -1-butanol NMR (CDC13, d): 1.10 (3H, d, J = 6.7 Hz), 2.09 ~ (1H, d, J = 14, 8Hz), 2.45 (1H, dd, J = 11.2 and 14.8 Hz), 3.1-3.3 (1H, m), 3.18 (2H, d, J = 12.8 Hz ), 3.91 (2H, d, J = 12.7 Hz), 6.82 (2H, d, J = 8.7 Hz), 7.11 (2H, d, J = 8.7 Hz), 7.2-7.3 (12H, m), 7.40 (2H, d, J = 9.4 Hz) (4) (9S) -l-Phenoxy-3- [N-benzyl- [(3RS- [1,1-bis (4-bromophenyl) -l-hydroxy-3-util] amino] -2-propanol MS m / z: 638.640 (M ++ l), 642 (5) N-Benzyl- [4, 4-bis (4-methoxyphenyl) butyl] -amine NMR (CDCl 3 d): 1.4-1.7 (2H, m), 2.00 (2H, quatrain, J = 7.8 Hz), 2, 64 (2H, t, J = 7.1 Hz), 3.75 (6H, s), 3.72-3.79 (3H, m), 6.80 (4H, d, J = 8.7 Hz), 7.11 (4H, d, J = 8.7 Hz), 7.28 (5H, s) MS m / z: 376 (M ++ l) (6) N-Benzyl- [3, 3-bis (4- ethoxyf enyl) propyl] -amine MS m / z: 390 (M ++ l) Preparation 5 1- [2, 2-Bis (4-methoxyphenyl) -2-hydroxyethyl] ci cl opent anol (0.79 g) were hydrogenated in a conventional manner in order to obtain 1- [2, 2-bis (4-me t oxy phenyl) and ti 1] ci cl opentane 1 (0.76 g). IR (Pure): 3563 (m), 3448 (m), 2956 (s), 1610 (w), 1510 (s), 1460 (m), 1246 (s), 1178 (m), 1036 (s), 829 (m) cm "1. NMR (CDC13, d): 1.5-1.9 (9H, m), 2.40 (2H, d, J = 7.3 Hz), 3.77 (6H, s), 4.17 (1H, t, J = 7.2 Hz), 6.81 (4H, d, J = 6.6 Hz), 7.21 (4H, d, J = 6.6 Hz) Preparation 6 To a mixture of 1- [2, 2-bis (4-me toxi-phe-1) -eti-1] -cyl-t-oneol (0.76 g), azi-do-trime-1 if 1-year (0, 32 g) and benzene (5 ml), boron trifluoride (0.34 ml) was added dropwise at 0 ° C. The reaction mixture was stirred at room temperature for 30 minutes and worked in a routine manner. The crude product was hydrogenated in a customary manner, in order to obtain [1- [2,2- bis (4-methoxyphenyl) ethyl] -cyclopentyl] -amine, (0.74 g).

IR (Pure): '2949 (s), 1610 (m), 1510 (s), 1460 (m), 1248 (s), 1178 (m), 1038 (s), 829 (s) cm "1 NMR (CDC13, d): 1.3-1.8 (10H, m), 1.20 (2H, t, J = 6.8 Hz), 3.77 (6H, s), 4.09 (1H, quartet, J = 6.8 Hz), 6.81 (4H, dd, J = 2.2 and 6.6 Hz), 7.14 (4H, d, J = 6.5 Hz.) MS m / z: 326 (M ++ l) Preparation 7 To a solution of dib in 1 i am a (1.14 g) and tetrahydrofuran (4 ml), butyllithium was incorporated. (1.54 M, in hexane, 3.7 ml) by dripping, at -78 ° C under a stream of nitrogen. After 30 minutes, a solution of 3 - (3,4-d ime t-oxy-1-acry-1-yl) acid ester (1.06 g) in tetrahydrofuran (3 ml) was added dropwise as well. , it was stirred for one hour and worked as it is routine. The crude product was purified by column chromatography with silica gel (hexane: ethyl acetate = 5: 1) in order to obtain methyl ester of 3 - (dibenzyl 1 amyl) -3- (3 , 4 -dime t ox if eni 1) pr opyontic (0.53 g). IR (Pure): 1739 (s), 1514 (s), 1458 (m), 1261 (m), 1146 (m), 1028 (m), 744 (m) cm "1. NMR (CDC13, d): 2.72 (1H, dd, J = 7.3 and 14.4 Hz), 3.07 (1H, dd, J = 8.6 and 14.4 Hz), 3.21 (lH, d, J = 13, l Hz), 3.65 (3H, s), 3.73 (2H, s), 3.79 (2H, s), 3.89 (6H, s), 4.25 (lH, t, J = 7.4 Hz), 6.75-6.90 (3H, m), 7.1-7.4 (10H,). Preparation 8 A mixture of 3- (dibenzylamino) -3- (3,4-dimethoxyphenyl) -propionic acid methyl ester (0.53 g), acetic acid (3 ml), methanol (3 ml), and sodium hydroxide 20% palladium on charcoal (0.05 g) was stirred under hydrogen (1 atm) at room temperature for 6 hours, filtered and evaporated in order to obtain methyl ester of 3-amino acid. 3 - (3,4-dimethoxy pheni 1) propionic (0.24 g). IR (KBr): 1729 (s), 1539 (s), 1523 (s), 1398 (m), 1265 (m), 1203 (m), 1155 (m), 1020 () cm "1 NMR (MeOH- d4, d): 1.90 (3H, s) 2.92 (2H, dd, J = 5.4 and 6.6 Hz), 3.63 (3H, s), 3.82 (3H, s) , 3.84 (3H, s), 4.52 (1H, t, J = 7.5 Hz), 6.95 (2H, s), 7.02 (1H, s) Preparation 9 To a solution of methyl ester hydrochloride of 3-aminopr-opyonic acid (1.12 g) in methanol 1 (10 ml), a 28% solution of sodium methoxide was added. anol (1.60 g), filtered and evaporated To the crude product, (2S) -2-f-enoxy-1,2-epoxyphenyl (901 mg) and methanol (10 ml) were added and stirred under reflux for 2.5 hours. The reaction mixture was evaporated and purified by column chromatography with silica gel, to obtain methyl ester of 3- [((2S) -2-hydroxy-3-f-enoxipr or i) ami no. ] pr op i on i co (0.76 g). IR (KBr): 1734 (s), 1601 (m), 1498 (m), 1435 (m), 1252 (s), 1196 (m), 1043 (m), 752 (m) cm "1 NMR (CDC13 , d): 2.54 (2H, t, J = 6.4Hz), 2.72- 2.98 (4H, m), 3.69 (3H, s), 3.97-4.07 (3H, m ), 6.90-6.99 (3H, m), 7.25-7.32 (2H, m) MS m / z: 254 (M ++ l) Preparation 10 The following compound was obtained according to a method similar to that used in Preparation 9. (3 RS) -3 - [((2 S) -2-hydroxy-3-phenoxypropyl) amino acid ester ] -3-phenyl-propionic. IR (KBr): 1724 (s), 1599 (m), 1495 (m), 1435 (m), 1246 (s), 1126 (m), 1038 (m), 756 (m), 698 (m), cm "1 NMR (CDCl 3, d): 2.54-2.75 (4H, m), 3.66 (1.5H, s), 3.67 (1.5H, s), 3.9-4 , 0 (2H, m), 4.0-4.2 (2H, m), 6.85-6.98 (3H, m), 7.2-7.4 (7H, m) MS m / z: 330 (M ++ l) Preparation 11 To a mixture of N-carbobenzyl-1-oxy-D- to 1-anan (0.81 g), [bi s (4-me t-oxy-phenyl) -methyl] -amine (0.80 g) , 1 -hi dr oxy -ben zotriaz ol (0.58 g) and N, N-dimethylformamide (5 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (0.76 g) was added. ), at 0 ° C and stirred at room temperature, for 30 minutes. After working as usual, N-ca was obtained rbobenci 1 ox i-D- to 1 aniña [bi s (4-me t oxy 1) me ti 1] -ami da (1.38 g) IR ( KBr): 3296 (s), 1689 (m), 1647 (s), 1539 (s), 1512 (s), 1257 (s), 1176 (m), 1031 (m) cm "1 NMR (DMSO-d6 , d): 1.21 (3H, d, J = 7, l Hz), 3.33 (6H, s), 4.17 (1H, t, J = 7.2 Hz), 5.01 (2H, s), 5.96 (1H, d, J = 8.4Hz), 6 , 86 (4H, d, J = 8.7Hz), 7.1-7.2 (4H, m), 7.3-7.5 (5H, m), 8.60 (lH, d, J = 8.5 Hz) Preparation 12 To a solution of N-ca rbobenzl 1-oxy-D-al aniña [bi s (4-me t oxy 1) me ti 1] ami da (0.33 g) in methanol and tetrahydrofuran (1: 2) , 10 ml), palladium on charcoal was added at 10%, with 50% humidity and stirred under an atmosphere of hydrogen (1 atm) for 30 minutes. After working as usual, D-alanine was obtained [b i s (4-me t oxi f eni 1) me t i 1] ami da (0.25 g). IR (Pure): 3357 (br 1678 (s) 1649 (s) 1538 (s), 1513 (s), 1259 (m), 1176 (m), 1032 (s), 831 (m), 812 (m) cm "1 NMR (DMSO-de, d): 1.13 (3H, d, J = 6.9 Hz), 3.33 (6H, s), 3.3-3.4 (3H, br), 5.96 (1H, d, J = 8.2 Hz), 6.87 (4H, d, J = 8.7 Hz), 7.15 (4H, d, J = 8.4 Hz), 8, 44 (1H, d, J = 8Hz) Preparation 13 To a solution of 4-methyl-ox bromide in i 1 -magnesium (1M in tetrahydrofuu, 35 ml) was added a solution of ethyl ester of 3- (dib ene i 1 ami no) -pr acid. Opium ion (4.87 g) in tetrahydrofuran (2 ml) was stirred under reflux for 1 hour, worked in the usual way and purified by column chromatography with silica gel (hexane: a ethyl acetate = 5: 1), in order to obtain 3-dibenzylamino-1,1-bis (4-methoxyphenyl) -1-propanol (3.45 g).

Preparation 14 3 - (Dibenz 1 ami no) -1,1-bi s (4-me toxy-phenyl-1) -1-propanol (2.0 g) was hydrogenated, by routine methods in order to obtain N-benz 1 - [ 3, 3-bis (4-me-toxi-phenyl-1) propy1] amine, which was rehydrated by heating with 20% palladium on charcoal and ammonium formate in methanol, to obtain [3, 3-bis (4 -me t oxi f eni 1) pr op i 1] amine (165 g).

Preparation 15 To a solution of 4-benzyl-1-oxy-3-nitrophenyl acetate (4.20 g) in methanol (20 ml), a 28% solution of sodium methoxide or methanol (2%) was added. 96 g) and evaporated. To the crude residue, N, N-d-ime-t-1-pyridine (20 ml) and (2S) -3- [(3-n-1-phenyl-1) its 1-oni-1-oxy] -1,2-epoxy were added. -pr opane (3.80 g). The mixture was stirred at room temperature overnight and worked in the usual manner in order to obtain (2S) -3-1,4-benzyl-1-oxy-3-nitrophenoxy) -1, 2 - epoxip r opane (4.30 g). NMR (CDC13, d): 2.72-2.77 (1H, m), 2.92 (1H, quintet, J = 4.8 Hz), 3.32-3.37 (1H, m), 3 , 91 (1H, quartet, J = 5.9 Hz), 4.27 (1H, dd, J = 2.8 and 11.4 Hz) 5.18 (2H, s), 7.07-7.15 (2H, m), 7.34-7.46 (6H, m).

Preparation 16 A mixture of 3 - (dibene-1-amine) -1,1 -bis (4-bromophenyl) -1-propanol (8.42 g), benzophenone-imine (10.8 g), di-palladium tris (dibenci 1 i den -a ce t ona) (546 mg), (RS) -2, 2'-bis (difenilf osf ino) 1, 1'-biphyl (1.11 g), tert-butoxide sodium (5.7 g) and toluene (90 ml) was stirred at 100 ° C for a period of 6 hours. The reaction mixture was added to tetrahydrofuran (300 ml) and 3N hydrochloric acid (300 ml) and stirred at room temperature for 1.5 hours. The aqueous phase was separated, neutralized by sodium hydroxide and extracted with ethyl acetate. The ethyl acetate solution was evaporated and purified; by column chromatography on silica gel (hexane: ethyl acetate = 1: 1) to obtain 3 - (dibenc i lami) - 1, 1 - 5b s (4-ami not f in i 1) -1-propanol (1.76 g). MS m / z: 438 (M ++ l) Preparation 17 The following compound was obtained according to a method similar to that used in Preparation 16. (3RS) -3- (Dibenzylamino) -1, 1-bis (4-aminophenyl) -1-butanol IR (Pure): 3356 (m), 3219 (m), 2964 (m), 1622 (s), 1512 (s), 1454 (m), 1383 (w), 1271 (m), 1246 (m), 1176 (m), 1142 (m), 831 (m) cm "1 NMR (CDCI3, d): 1.03 (3H, d, J = 6.7 Hz), 2.02 (1H, d, J = 11, 7 Hz), 2.50 (1H, dd, J = ll, 2 and 14.7 Hz), 3.10-3.2 (1H, m), 3.21 (2H, d, J = 13 , 0 Hz), 3, 92 (2H, d, J = 12.9 Hz), 6.35 (2H, d, J = 6.5 Hz), 6.55 (2H, d, J = 6, 6 Hz), 6.76 (2H, d, J = 6.6 Hz), 7.13 (2H, d, J = 6.5 Hz), 7.24 (10H, s) MS m / z: 452 (M + + l).

Preparation 18 To a mixture of 3- (dibenzyl-amino) -1,1-bis (4-aminophenyl) -1-propanol (0.64 g), pyridine (0.5 ml) and dichloromethane (10 ml), added methyl chlorocarbonate (0.34 ml) at 0 ° C and the reaction mixture was worked up in the usual manner. The crude product was dissolved in methanol (10 ml), followed by the addition of 4N hydrogen chloride in 1,4-dioxane (0.5 ml) and 20% palladium on carbon hydroxide. The mixture was stirred under hydrogen (1 atm) at room temperature, overnight, worked in a similar manner, and purified by column chromatography on silica gel (di c in g or not: me t a n o 1: a gua concentrated ammonia = 20: 1: 0.1), to obtain N-benzyl- [3, 3-bis [(methoxycarbonyl) -amino] phenyl] -propyl] amine (466 mg).

Preparation 19 A mixture of (3-RS) -3-naphthalethyl methylester hydrochloride (5.0 g), benzyl bromide (11.7 g), potassium carbonate (18 g) and N, N-dimetho-1-formamide (40 ml) was stirred at room temperature overnight, worked in the usual way and purified by column chromatography with silica gel (hexa no: ethyl acetate = 15: 1). ) in order to obtain (3-RS) -3- (dibenz-1-amino-1-buto) methyl ester (7.27 g). IR (Pure): 2958 (m), 1741 (s), 1454 (m), 1259 (m), 1196 (m), 1146 (m), 1072 (m), 1022 (m), 744 (m), 698 (m) cm "1 NMR (CDC13, d): 1.10 (3H, d , J = 6.7 Hz), 2.28 (1H, dd, J = 6.9 and 13.9 Hz), 2.64 (1H, dd, J = 8.01 and 13.9 Hz), 3 , 30 (1H, dd, J = 6.8 and 14.7 Hz), 3.44 (2H, d, J = 13.7 Hz), 3.60 (3H, s), 3.66 (2H, d, J = 13.7 Hz), 7.18-7.35 (10H, m) MS m / z: 298 (M + + l) Preparation 20 The following compound was obtained according to a method similar to that used in Preparation 19. (3-RS) -3- [N-Benz 1 - ((2S) -2-hydroxy-3-methyl) ether phenoxypropyl) -amino] butyric acid. MS m / z: 358 (M ++ l) Preparation 21 To a mixture of (3 RS) -3- (dibenz 1 amino) -1, 1-bis (4-aminophenyl) -1-butanol (360 mg), triethylamine (0.44 ml) and dichloromethane (4 ml) ), methanesulfonyl chloride (0.20 ml) was added dropwise at 0 ° C. The reaction mixture was stirred at room temperature for 30 minutes and worked by routine procedures. The crude product was dissolved in methanol, followed by the addition of 10% palladium on charcoal (50% moisture) and ammonium formate, heated under reflux for 1.5 hours, filtered and extracted by water. The aqueous solution was treated with benzyl chlorocarbonate (136 μl) with the usual Shotten method, worked in the usual way and purified by column chromatography with silica gel (hexane or: ethyl acetate = 2: 3), In order to obtain acid benzyl ester (3RS) - [3, 3-bis [4- (methanesulfonylamino) phenyl] -l-methylpropyl] -carbamic acid (138 mg). IR (Pure): 3259 (m), 1680 (s), 1512 (s), 1331 (m), 1153 (s), 974 (m) cm "1 NMR (CDC13, d): 1.13 (3H, d, J = 6.8 Hz), 2.4-2.6 (2H, m), 2.98 (6H, s), 3.7-3.9 (1H, m), 4.6-4 , 8 (1H, m) 6.52 (2H, s), 7.07-7.15 (5H, m), 7.2-7.5 (8H, m) Preparation 22 (3RS) -1,1-Bis [4 - (methanesulf oni 1 amino) pheny1] -3-bu ti 1 amine (77.4 mg) was obtained from the benzyl ester of acid (3RS) - [3, 3-bis [4- (methanesulfonylamino) phenyl] -l-methylpropyl] carbamic acid (101 mg) by hydrogenation in the usual manner. IR (KBr): 3425 (br s), 1635 (m), 1506 (m), 1325 (m), 1151 (s), 1103 (), 980 () cm "1 NMR (MeOH-d4, d): 1.13 (3H, d, J = 6.4 Hz), 2.05 (2H, quartet, J = 7.7 Hz), 2.73 (1H, quartet, J = 6.5 Hz), 2.89 (6H, s) 4.06 (1H, dd, J = 7.8 Hz and 14.8 Hz), 7.16 (4H, d, J = 8.5 Hz), 7.26 14H, d, J = 8.5 Hz) MS m / z: 12 (M ++ l).

Preparation 23 To a mixture of (3 RS) -3- (dibenz 1 ami no) -1, 1 -bi s (4-aminophenyl) -1-bu t anol (0.40 g), triethylamine (0.37 ml) and dichloromethane ( 4 ml), acetic anhydride (0.18 ml) was added at 0 ° C, followed by the addition of additional triethylamine (0.1 ml) and acetic anhydride (0.09 ml). The reaction mixture was worked up in the usual manner, in order to obtain (3 RS) -3- (d ib in ci 1 ami no) -1,1 -bis [4 - (α-ti ti -mino) phen i 1] - 1 -bu t anol (0.49 g) IR (Pure): 2300 (m), 1666 (s), 1623 (m), 1539 (s), 1514 (m), 1319 (m), 1265 (m) ), 1142 (w), 837 (m) cm "1. NMR (CDC13, d): 1.06 (3H, d, J = 6.6 Hz), 2.12 (3H, s), 2.16 (3H, s), 2.0-2.2 (lH, m), 2.45-2.58 (1H, m), 3.0-3.2 (1H, m), 3.20 (2H , d, J = 12.9 Hz), 3.92 (2H, d, J = 13.0 Hz), 6.72 (2H, d, J = 6.8 Hz), 7, 09-7, 36 (16H , m) MS m / z: 536 (M + + 1) Preparation 24 (3RS) -3-amino-1,1-bis [4 - (acetylamino) phenyl] -1-butanol (0.23 g) was obtained from (3RS) -3- (dibenzylamino) - 1,1-bis [4- (acetylamino) phenyl] -1-butanol (0.39 g) by customary hydrogenation.

IR (KBr): 3294 (m), 1666 (s), 1623 (s), 1537 (s), 1514 (), 1406 (m), 1321 in), 1014 (m) cm "1 NMR (MeOH-de , d): 1.10-1.15 (3H, m), 2.07 (3H, s), 2.11 (3H, s), 2.5-3.1 (3H, m), 4, 23 (2H, d, J = 10.6 Hz), 4.55 (2H, d, J = 10.6 Hz), 7.21-7.58 (8H, m).

Preparation 25 The following compound was obtained according to a method similar to that used in Example 33. (3RS) -3- (Dibenzylamino) -1, 1-bis [4- (methoxy-carbonyl-amino) phenyl] -1-butanol MS m / z: 568 Preparation 26 (3-RS) -1,1 -B is [4 - (me toxy carboni 1 amino) phenyl] -3-bu ti 1 amine hydrochloride (191 mg) from (3 RS) - 3 - (dibenz 1 amino) -1,1-bi s (4-methoxycarbonyl-1-ami no-phenyl-1-butanol) (173 mg), by hydrogenation, in the usual manner. MS m / z: 372 (M ++ l) (free) Preparation 27 Methanesulfonyl chloride was incorporated (1.4 ml) dropwise to a solution of 3-amino-4-beta-cycloxyloxyfluoryl acetate (4.3 g), in pyridine. (20 ml) under cooling with ice, for a period of 10 minutes and the mixture was stirred at room temperature, for an additional 1 hour. To the reaction mixture was added water (100 ml) and stirred at the same temperature for 1 hour. The precipitates were collected by filtration and dissolved in chloroform (100 ml), dried in magnesium sulphate and evaporated in vacuo. The residue was subjected to chromotography (hexane-ethyl acetate) on silica gel, to obtain 4-benzyloxyl-3 - (methan-sulfonylamino) phenyl acetate (1.6 g). NMR (CDC13, d): 2.27 (3H, s), 2.95 (3H, s) 5.09 (2H, s), 6.80-7.03 (3H, m), 7.25- 7.45 (6H, m) MS m / z: 336 (M + + l) Preparation 28 A solution of 4-benzyl-1-oxy-3-acetate (me t ans ul oni 1 amino) f eni 1 o ( 1.6 g) and potassium hydroxide (2.67 g) in methanol (10 ml) was stirred for 18 hours at room temperature. The reaction mixture was acidified with IN hydrochloric acid to pH 5-7 and extracted with ethyl acetate. ethyl. The organic layer is washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was subjected to chromatography (ethyl acetate-hexane) on silica gel to give N- (2-benzyl-1-oxy-5-hydr-oxy-phi-1) me t an s on phona (750 mg) NMR (CDC13, d): 2.90 (3H, s), 5.04 (2H, s), 6.58 (1H, dd J = 2, 9 and 8.8 Hz), 6.80-6.90 (2H, m), 7.09 (1H, d), J = 2, 9 Hz), 7.30-7.50 (6H, m) MS m / z: 294 (M + + l).

Preparation 29 Under nitrogen, to a solution of N- (2-benzyl oxy-5-hydr oxy phenyl) me t ans ul f onami da (740 mg) and sodium hydride (92.4 mg) in N, N-dimethylformamide (30 ml) (2 S) -gl i ci di 1 o (616 mg) tosylate was added at 0 ° C and the mixture was stirred at the same temperature for 0.5 hours. The mixture was allowed to warm to room temperature and was stirred for 2.5 hours at the same temperature. The resulting mixture was poured into 10% aqueous ammonium chloride solution, and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated in vacuo. The residue was subjected to chromatography on silica gel (hexane-ethyl acetate), to obtain (2S) -3- [4-benzyl-1-oxy-3 - (methanesulfonamino) phenoxy] -1,2-epoxypropane (440 mg). MS m / z: 350 (M ++ l).

Preparation 30 Under nitrogen, a solution of N-benzyl- [3, 3-bis (4-methoxyphenyl) -l-methylpropyl] amine (480 mg), N- [2-benzyloxy-5- [(IR) -2- iodine-l- (tr ie ti 1 si 1 i 1 oxy) eti 1] f eni 1] -me t an s ul phonami (600 mg) and N, N-di is opropyl-et ylamine (0.74) ml) in tetrahydrofuran (6 ml) was sealed with stirring, at 110 ° C for 58 hours and then at 160 ° C - for 92 hours. The resulting mixture was poured into aqueous sodium hydrogen sulfide and extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium bicarbonate and brine, dried over anhydrous sodium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 10: 5: 1), to obtain N - [5 - [(1 R) -2 - [N-benzyl] - [(1 RS) -3,3-bis (4-methoxyphenyl) -l-methylpropyl] amino] -1- (triethylsilyl-oxy) -ethyl] -2- (benzyloxy) phenyl] methansulfonamide (226 mg).

NMR (CDCI3, d): 0.25-0.5 (6H, m), 0.7-0.95 (12H, m) 1.5-2.25 (2H, m), 2.35-2.9 (6H, m) 3.45- 3.9 (8H, m), 4.25-4.4 (1H, m) 5.0-5.1 (2H, m), 6, 65-7, 75, (21H, m) Preparation 31 The N-enz hydrochloride 1 - [(1 S) -3,3-bis (4-methyl-1-phenyl) -1-methylpropyl] -amine (800 mg) was subjected to hydrochloric acid. The mixture was saturated aqueous sodium bicarbonate and extracted with ethyl acetate. A mixture of the product obtained above and palladium on activated carbon at 10% (50% humidity, 300 mg) in methanol (10 ml) was stirred at room temperature, in the presence of hydrogen at atmospheric pressure, for 5.5 hours. After filtration, the filtrate was evaporated in vacuo in order to obtain [(1S) -3,3-bis (4-methoxyphenyl) -1-methyl-1-opi] amine (568 mg). NMR (CDCl 3, d): 1.10 (3H, d, J = 6.3 Hz), 1.95-2", 1 (2H, m), 2.7-2.9 (1H, m), 3.76 (6H, m), 3.98 (1H, t, J = 8.0 Hz), 6.75-6.9 (4H, m), 7.1-7.2 (4H, m) Preparation 32 The following compound was obtained according to a method similar to that used in Preparation 31. [(IR) -3,3-Bis (4-methoxyphenyl) -l-methylpropyl] amine. NMR (CDC13, d): 1.19 (3H, d, J = 6.3 Hz), 1.9-2.1 (2H, m), 2.7-2.85, (1H, m), 3.76 (6H, m), 3.98 (1H, t, J = 7.9 Hz), 6.75-6.9 (4H, m), 7.15 (4H, d, J = 8, 0 Hz) Preparation 33 A mixture of N-benzyl- [3, 3-bis (4-hydroxy-1-yl-1-methyl-1-methyl) (300 mg) and palladium on activated charcoal 10% (50 mg). % humidity, 100 mg) in methanol (5 ml) was stirred at room temperature, in the presence of hydrogen at atmospheric pressure for 4 hours. After filtration, the filtrate was evaporated in vacuo, in order to obtain [3, 3-bi s (4-i d oxy f in i 1) -methylpropyl] amine (230 mg). NMR (DMSO-de, d): 0.96 (3H, d, J = 6.3 Hz), 1.75-1.9 (2H, m), 2.4-2.6 (1H, m) , 3.87 (1H, t, J = 7.9 Hz), 6.63 (4H, d, J = 8.5 Hz), 7.03 (4H, d, J = 8, 2 Hz) Preparation 34 The following compound was obtained according to a method similar to that used in Preparation 33. N-Benzyl- [3, 3-bis (4-ethoxyphenyl) -l-methylpropyl] amine.

Preparation 35 A mixture of 6- [(4-nitrophenyl) azo] pyridin-3-ol (J. Am. Chem. Soc. 1959, 81, 6049, 300 mg) and 20% palladium on charcoal hydroxide (60 mg ), in a mixture of acetic acid (30 ml) and methanol (30 ml), was stirred at room temperature in the presence of hydrogen at atmospheric pressure for 70 minutes. After filtration, the filtrate was evaporated in vacuo. Under nitrogen to a mixture of the residue in dichloromethane (10 ml), bis (trimethylsilyl) -acetamide (6.0 ml) was added at 5 ° C. After being stirred at room temperature for 30 minutes, to the resulting mixture was added benzyl chloroformate (0.54 ml) at 5 ° C and the mixture was stirred at the same temperature for 3 hours. The resulting mixture was poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried on anhydrous magnesium sulfate and evaporated in vacuo. Chloroform was added to the residue and the insoluble materials were removed by filtration. After the filtrate was evaporated in vacuo, the residue was purified by column chromatography on silica gel (gold formaldehyde: me tanol = 50: 1 to 20: 1), followed by crystallization from toluene-methanol , in order to obtain acid benzyl-ester (5-hydroxy-dihydroxy-2-yl) -carbamate (159 mg). MS m / z 245 (M ++ l).

Preparation 36 Under nitrogen, a suspension of sodium hydride (60% in oil, 189 mg) in N, N-dimethylformamide (20 ml) was added dropwise to the benzyl ester of acid (5-hydroxyhydrate). -i 1 o) ca rbámi co (1.1 g) in N, N-dime ti 1 formamide (12 ml) at 5 ° C and the mixture was stirred at room temperature for 1 hour. To it was added tosylate of (2 S) -g 1 i cidi 1 or (1.1 g) at 5 ° C and the mixture was stirred at room temperature, for 7 hours. The resulting mixture was poured saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and evaporated in vacuo The residue was purified by column chromatography on silica gel (cl or of orm: ethyl acetate = 9: 1), to obtain (2S) -3- [2- (benzyloxycarbonylamino) pyridin-5-yloxy. ] -1, 2-epoxypropane (780 mg). MS m / z: 301 (M ++ 1).

Preparation 37 To a suspension of bu t-3-eni lb. (3 ml) and sodium bicarbonate (2.5 g) in a mixture of di chlorine (200 ml) and water (60 ml) were added small portions of cl or ope rbenz oí co acid (3.5 g), at room temperature and the mixture was stirred at the same temperature, for 4 hours. After separation, the organic layer was washed successively with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (ethyl hexane to 100: 3) in order to obtain 1-oxigen (970 mg). NMR (CDC13, d): 1.7-1.9 (2H, m), 2.45-2.5 (1H, m), 2.7-3.0 (4H, m), 7.1- 7.4 (5H,).

Preparation 38 Under nitrogen, to a solution of tosylate of (2R) -gl i cidi 1 or (3.0 g) in tetrahydrofuran (30 ml) were added N, N-diis or r op i 1 eti 1 amine (2.5 ml) and thiophenol (1.3 ml) at 5 ° C and the mixture was stirred at room temperature, for 125 hours. The resulting mixture was poured into water and extracted with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium bicarbonate and brine, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 5: 3: 1), in order to obtain (2 S) -hi dr oxy-3 - (f-enyl thio) pr op i 1-Phosphoric acid ester oluen-4-s (3.9 g). NMR (CDC13, d): 2.44 (3H, m), 2.75-3.25 (3H, m), 3.85-4.3 (3H, m), 7.15-7.4 ( 7H, m), 7.7-7.8 (2H, m).

Preparation 39 Under nitrogen, to a solution of (2S) -2-hydroxy-3-y (f eni 11 io) pr op i 1-toluene-4-sulfonic acid ester (3.9 g) in ethanol ( 40 ml) was added 20% sodium methoxide in ethanol (4.7 ml) at 5 ° C and the mixture was stirred at the same temperature for 30 minutes. After being filtered to eliminate the precipitates, the filtrate was concentrated in vacuo. The residue was dissolved in a mixture of 0.01N aqueous sodium hydroxide and diethyl ether. After separation, the organic layer was washed successively with water and brine, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 20: 10: 1) in order to obtain (2S) -3- (f eni 11 io) - 1, 2 - epoxypropane (1.5 g). MS m / z: 167 (M ++ l) EXAMPLE 6 The solution of 4-b as t i or a n i s 1 (508 mg) in tetrahydrofuran, butyllithium (1.54 M in hexane, 162 ml) was added at -78 ° C. After 30 minutes, (3RS) -3 - [((2S) -2-Hydr-oxy-3-f-enoxipr-opy-1-o) amy nobutoic acid ester (131 mg) was added and it was warmed to 0 ° C. The reaction mixture was worked up in the usual way and purified by column chromatography on silica gel, so as to obtain (2S) -1-f-enox i -3 - [(3RS) -1,1 -bi. s [4 - (methylthio) phenyl] -l-hydroxy-3-butyl] amino-3-propanol (58.5 mg).

IR (Pure): 3400 (br s), 2921 (s), 1594 (s), 1492 (s), 1243 (s), 1093 (m), 1043 (m), 817 (s), 754 (s) NMR (CDC13, d): 1.14 (3H, d, J = 6.3 Hz), 2.4-2.6 (2H, lOm), 2.43 (3H, s), 2.46 (3H , m), 2.7-2.8 (2H, m), 2.88 (1H, dd, J = ll, 9 and 8.0 Hz), 3.9-4.1 (3H,), 6 , 9-7.0 (3H, m), 7.1-7.4 (12H, m).

Example 7 The following compounds were obtained according to a method similar to that used in Example 6. (1) (2S) -l-Phenoxy-3- [(3RS) -1, 1-bis (3 -methoxyphenyl) -l-hydroxy-3-butyl] amino-2-propanol IR (Pure): 3296 (br m), 2933 (s), 1599 (s), 1491 (s), 1464 (m), 1246 (s), 1171 (m), 1045 (s), 756 (m), 694 (m) cm "1 NMR (CDCI3 + D20, d): 1.09 (3H, d, J = 6.3 Hz), 2.04 (1H, dd, J = ll, 4 and 14.2 Hz), 2.39-2.49 (2H, m), 2.6-2.8 (lH, m), 2 , 83 (lH, dd, J = 8.3 and 11.9 Hz), 3.74 (3H, s), 3.76 (3H, s), 3.8-3.9 (2H, m), 3.9-4.1 (1H, m), 6.72-6.75 (2H, m), 6.8-7.1 (7H, m), 7, 12-7, 31 (4H, m) MS m / z: 452 (M ++ l) (2) (2S) -l-Phenoxy-3- ((3RS) -1,1-diphenyl-1-hydroxy-3-butyl) amino-2-propanol IR (Pure): 3299 (br m), 3925 (m), 1597 (m), 1495 (s), 1456 (m), 1244 (s), 1043 (m), 754 (s), 698 (s) MS m / z: 392 (M + +) (3) (2S) -l-Phenoxy-3- [(3RS) -1,1-bis (4-methoxyphenyl) -l-hydroxy-3-butyl] amino -2-propanol IR (Pure): 3292 (br m), 2929 (m), 1604 (m), 1508 (s), 1460 (m), 1248 (s), 1176 (m), 1038 (m), 833 (m), 756 (m) cm "1 NMR (CDC13, d): 1.12 (1.5H, d, J = 5, l Hz), 1.16 (1.5H, d, J = 6 , 2 Hz), 2.0-2.5 (2H, m), 2, 6-3.2 (3H, m), 3.74 (1.5H, s), 3.75 (1.5H, s), 3.78 (3H, s), 3.8-4.2 (3H, m), 6.77-7.01 (7H, m), 7.2-7.4 (6H, m) MS m / z: 452 (M + +) (4) (2S) -l-Phenoxy-3- [(3RS) -1,1-bis (3,4-methoxyphenyl) -l-hydroxy-3-butyl ] amino-2-propanol IR (Pure): 3294 (br m), 2933 (m), 1597 (w), 1510 (s), 1460 (m), 1257 (s), 1146 (m), 1028 (m) 760 (m) MS m / z: 512 (M ++ 1) (5) (2S) -l-Phenoxy-3- [(3RS) -l, 1-bis (4-methylphenyl) -l-hydroxy-3-butyl] amino -2-propanol IR (Pure): 3400 (br s), 2923 (s), 1596 (m), 1498 (s), 1457 (s), 1243 (s), 1087 (m), 1043 (m), 817 (s) , 754 (s) cm "1 NMR (CDC13, d): 1.13 (2H, d, J = 6.2 Hz), 2.16 (3H, s), 2.31 (3H, s), 2 , 4-2.5 (2H, m), 2.6-2.9 (3H, m), 3.9-4.1 (3H, m), 6.9-7.4 (13H, m) MS m / z: 420 (M + +) (6) 5- [N-Benzyl- ((2S) -2-hydroxy-3-phenoxy-propyl) amino] -1,1-bis (4-methoxyphenyl) -1-pentanol IR (Pure): 3446 (br m), 2943 (m), 1604 (), 1508 (s), 1458 (m), 1248 (s), 1176 (m), 1036 (m), 831 (m), 752 (m) cm "1 NMR (CDCl 3, d): 1.2-1.3 (2H, m), 1.4-1.7 (2H, m), 2.1-2, 2 (2H, m), 2.4-2.7 (4H, m), 3.4-3.6 (1H m) 3, 7 6H, 3.7-3.8 (1H, m), 3.8-3.9 (2H, m), 3.9-4.1 (1H, m) 6.77-6.97 (7H, m), 7.2-7.4 (11H, m) MS m / z: 556 ( M ++ l) (7) 4- [N-Benzyl- ((2S) -2-hydroxy-3-phenoxypropyl) amino] -1,1-bis (4-methoxyphenyl) -1-butanol IR (Pure): 3446 (br m), 2951 (), 1604 (m), 1508 (s), 1458 (m), 1248 (s), 1176 (m), 1036 (s), 831 (m), 752 (m) cm "1 NMR (CDCl 3, d): 1.5-1.7 (2H, m), 2.1-2.4 (2H, m), 2.4-2.7 (4H, m), 3.4- 3.5 (1H, m), 3.77 (6H, s), 3.7-3.8 (1H, m), 3.8-4.0 (2H,), 4.1-4.3 (1H, m), 6.78-6.98 (7H, m), 7.2-7.4 (11H, m) MS m / z: 542 (M ++ l) (8) (2S) - l-Phenoxy-3- [(lRS) -3,3-bis (4-methoxyphenyl) -3-hydroxy-1- (3, -dimethoxyphenyl) propyl] amino-2-propanol IR (Pure): 3361 (br m ), 2929 (m), 1602 (m), 1512 (s), 1459 (m), 1248 (s), 1032 (s), 833 (m), 756 (m) cm "1 NMR (CDCI3, d) : 2,3-2,8 (5H, m), 3,74 (3H, s), 3,82 (3 H "," s), 3,86 (6 H, s), 3,9-4 , 1 (3H, m), 6.6-7.1 (8H, m), 7.2-7.5 (8H, m) MS m / z: 574 (M + + l) (9) (2S) -l-Phenoxy-3- [(1RS) -3,3-bis (4-methoxyphenyl) -3-hydroxy-1-phenylpropyl] amino-2-propanol IR (Pure): 3361 (br m), 2929 (m ), 1603 (m), 1506 (s), 1458 (m), 1246 (s), 1176 (m), 1035 (m), 833Cm), 756 (m), 698 (m) cm "1 NMR (CDCI3) , d): 2.3-2.8 (4H, m), 3.6-3.7 (1H, m), 3.74 (3H, s), 3.82 (3H, s), 3, 8-4.2 (4H, m), 6.7-7.0 (9H, m), 7.1-7.2 (2H, m), 7.2-7.4 (5H,), 7 , 4-7.5 (2H, m) MS m / z: 514 (M ++ 1) (10) (2S) -l-Phenoxy-3- [3, 3-bis (4-methoxyphenyl) -3-hydroxyphenyl] amino-2-propanol IR (Pure) : 3313 (br m), 2931 (m), 1602 (s), 1508 (s), 1462 (m), 1248 (s), 1176 (m), 1036 (m), 831 (m), 756 (m) ) cm "1 NMR (CDC13 + D20, d): 2.3-2.5 (2H, m), 2.7-2, 9 (4H, m), 3.77 (6H, s), 3, 9-4.2 (4H, m), 6.80-7.01 (7H, ~ m), 7.2-7.4 (6H, m) MS m / z: 438 (M ++ l) Example 8 The following compounds were obtained according to a method similar to that used in Preparation 33. (1) (2 S) -1-Phenoxy-3 - [5, 5-bis (4-methoxyphenyl) hydrochloride) pentyl] -amino-2-propanol IR (Pure): 3322 (br m), 1602 (m), 1510 (s), 1460 (m), 1246 (s), 1178 (m), 1036 (m), 831 (m) cm "1 NMR (MeOH-d4, d): 1.2-1.4 (2H, m), 1.6-1.8 (2H, m), 2.04 (2H, quartet, J = 7.5 Hz), 2.99 (2H, t, J = 8.0 Hz), 3.09-3.22 ~ (2 H, m), 3.73 (6H, s), 3.6-3.85 (1H, m), 3.9-4.0 (2H, m), 4.1-4.3 (1H, m) , 6.84 (4H, d, J = 8.7 Hz), 6.9-7.0"(3H, m), 7.14 (4H, d, J = 8.6 Hz), 7.28 (2H, t, J = 7.9 Hz).

MS m / z: 450 (M ++ 1) (free) (2) (2 S) -1-Phenoxy-3 - [4, 4-bis (4-methoxyphenyl) butyl] -amino-2-propanol hydrochloride IR (Pure): 3355 (br m), 1602 (m), 1510 (s), 1460 (m), 1246 (s), 1178 (m), 1036 (m), 831 (m) cm "1 NMR ( MeOH-d4, d): 1.6-1.8 (2H, m), 2.08 (1H, quartet, J = 7.9 Hz), 2.55 (1H, quartet, J = 7.6 Hz ), 3.0-3.2 (4H, m), 3.73 (6H, s), 3.7-4.3 (4H, m), 6.8-7.0 (7H, m), 7.1-7.4 (6H, m) MS m / z: 436 (M ++ l) (free) Example 9 A mixture of (2 S) -1-f-enoxyl i-3 - [(3 RS) -1,1 -bis [4- (methylthio) phenyl] -l-hydroxy-3-butyl] amino-2- Propanol (47 mg), water (2 ml), methanol (3 ml) and OXONE® (potassium peroxymonosulfate) (180 mg) were stirred at room temperature, overnight and worked in the usual manner, in order to obtain (2S) -l-phenoxy-3- [(3RS) -1,1-bis (4-ethanesulfonylphenyl) -l-hydroxy-3-butyl] amino-2-propanol (52 mg). IR (Pure): 3521 (br m), 2927 (m), 1595 (m), 1494 (s), 1309 (s), 1244 (m), 1149 (s), 1091 (m), 958 (m), 771 (s), 694 (m) cm -i NMR (CDCl 3, d) f 1.19 (3 H, d, J = 6.3 Hz), 2.3-2.8 (4 H, m), 2.9 (1 H, m), 3.00 (3 H , s), 3.5 (3H, s), 3.9-4.1 (3H, m), 6.9-7.1 (3H, m), 7.2-7.4 (1H, m ), 7.5-7.74 (5H, m), 7.8-7.9 (4H, m) MS m / z: 548 (M ++ l) EXAMPLE 10 A mixture of (2S) -3-f-enoxy-1,2-epoxypropane (40 mg), 3-amino-3- (3,4-dimethoxyphenyl) propionic acid methoxy ester (80 mg), triethylamine (0.5 ml) and methanol (3 ml) was heated under reflux, evaporated and purified by column chromatography on silica gel (hexane: ethyl acetate: methanol = 1: 1: 0.07), in order to obtain (3RS) -3- ((2S) -2-hydroxy-3-phenoxypropyl) -amino-3-methyl ester. - (3, 4-dimethoxy-phenyl) p rop i óni co (92 mg). IR (Pure): 2925 (m), 1738 (s), 1597 (m), 1514 (s), 1460 (m), 1263 (), 1138 (m), 1027 (s), 758 (m! NMR (CDCl3, d): 2.6-2.8 (4H, m), 3.67 (3H, s), 3.87 (6H, s), 3.9-4.0 (2H, s) , 4.0-4.1 (2H, m), 6.8-7.0 (7H, m), 7.26 (1H, t, J = 8.9 Hz) MS m / z: 390 (M ++ l) Example 11 The following compound was obtained according to a method similar to that used in Example 10. (2S) -l-Phenoxy-3- [1,1-bis (4-methoxy-enyl) - 3-methyl-3-butyl] ami-2-propanol IR (Pure): 3350 (br m), 2962 (m), 1606 (m), 1508 (s), 1460 (m), 1248 (s) , 1178 (m), 1036 (m), 829 (m), 756 () cm "1 NMR (CDC13, d): 1.03 (3H, s), 1.05 (3H, s), 2.22 (2H, d, J = 6.8 Hz), 2.55 (1H, dd, J = 7.0 and 11.7 Hz), 2.68 (1H, dd, J = 3.6 and 11.7 Hz), 3.73 (6H, s), 3.8-3.9 (3H, m), 4.04 (1H, t, J = 6.7 Hz), 6.77-6.99 (7H,), 7.1-7.4 (6H, m) MS m / z: 450 (M ++ l) Example 12 A mixture of (2S) -3-f-enoxi-1, 2-epoxypropane (0.12 g), l- [2,2-bis (4-methoxyphenyl) -e ti 1] ci cl open til amine (0.24 g) and methanol (5 ml) was heated under reflux, evaporated and purified by column chromatography on silica gel (hexane: ethyl acetate: methanol = 1: 1: 0.07), order to obtain N- ((2 S) - 2 -hi dr oxy - 3 - f enox ip r op i 1 o) - [1 - (2,2-bis (4-methoxyphenyl) ethyl] -cyclopentyl] amine (40.9 mg): IR (Pure): 2954 (m), 1606 (w), 1510 (s), 1460 (m), 1246 (m), 1176 (m), 1038 (s), 825 (m), 754 (m) cm NMR (CDC13, d): 1.2-1.8 (8H, m), 2.25 (2H, t, J = 6.8 Hz), 2.46 (1H, dd, J = 6.9 and 12.0 Hz), 2.61 (1H, dd, J = 4.4 and 12.0 Hz), 3.73 (6H, s), 3.8-3.9 (2H, m), 4.0-4.1 (2H, m), 6.78 (4H, d, J = 8.2 Hz), 6.9-7.0 (3H, m), 7.19 (4H, d, J = 8.7 Hz), 7.24-7.33 (2H, m) MS m / z: 476 (M + + l) EXAMPLE 13 The following compounds were obtained according to a method similar to that used in Example 12. (1) (lR) -l- (3-Pyridyl) -2 - [[(3RS) -1, 1-bis (4-methoxyphenyl) -3-butyl] amino] -ethanol MS m / z: 407 (M + + l) (2) (2 S) - 1 - (3-P iri di 1 ox i) dihydrochloride) -3- [(3RS) -1, 1-bis (4-methoxyphenyl) -3-butyl] amino-2-pr opane 1 MS m / z: 437 (M ++ l) (free) (3) (2R) -1- (1 H -indol-4-yloxy) -3- [3, 3-bis (4-methoxyphenyl) -propyl] amino-2-propanol MS m / z: 461 (M ++ l) (4) (2RS) -1- (2-Oxo-2), 3-dihydro-lH-benzimidazol-4-yloxy) -3- [(3 RS) -1,1-bis (4-methoxyphenyl) -3-butyl] amino-2-propanol MS m / z: 492 (M ++ l) (5) (2R) -3- [4-Benzyloxy-3- (methanesulfonylamino) phenyl] -1- [(3RS) -1,1-bis (4-methoxyphenyl) -3-butyl] amino- 2-propanol (6) (2S) -l-Phenoxy-3- [(3RS) -l, l-bis [4- (methanesulfonyl-amino) phenyl] -3-butyl] amino-2-propanol IR (KBr) : 3440 (br s), 1603 (m), 1508. { m), 1325 (), 1242 (m), 1151 (s), 1103 (m), 974 (m), 758 (m) cm "1 NMR (CDC13, d): 1.11 (3H, d, J = 6.2 Hz), 2.0-2.2 (2H, m), 2.2-2.9 (3H, m), 2.97 (6H, s), 3.9-4.0 ( 3H, br s), 4.1-4.2 (1H, m), 6.88-7.00 (4H, m), 7.10-7.33 (9H, m) MS m / z: 562 (M ++ 1) (7) (2S) -l-Phenoxy-3- [(3RS) -1,1-bis [4- (acetylamino) phenyl] -l-hydroxy-3-butyl] amino-2- propanol MS m / z: 506 (M ++ l) (8) (2S) -l-Phenoxy-3- [(3RS) -l, l-bis [4-acetylamino) phenyl] -3-butyl] amino-2-propanol MS m / z: 490 (M + + l) Example 14 A mixture of (1S) -1-f-enoxyl-3 - [3, 3-bis (4-methoxyphenyl) -3-hydroxypropyl] amino-2-propanol (93 mg), p-hydrate toluene sulfonic acid (53 mg) and toluene was heated under reflux for 1.5 hours, evaporated and purified (preparative TLC, silica gel, 10% me ta no 1-di or orne no), to obtain - (SS) -l-phenoxy-3- [3, 3-bis (4-methoxyphenyl) -2-pr open i 1] ami no-2-propanol (80.5 mg). IR (Pure): 3359 (br m), 1604 (s), 1510 (s), 1460 (m), 1248 (s), 1176 (m), 1034 (m), 835 (m), 756 (m) , 686 (m) cm "1 NMR (CDC13 + D20, d): 2.9-3.1 (2H, m), 3.58 (2H, d, J = 7.0 Hz), 3.77 ( 3H, s), 3.82 (3H, s), 3, 9-4.0 (2H, m), 4.2-4.3 (1H, m), 6.07 (lH, t, J = 7, l Hz), 6.73-7.29 (13H, m) Example 15 To a mixture of (2S) -1-f-enoxyl-3 - [3, 3-bis (4-methoxyphenyl) -3-hydroxypropyl] amino-2-propanol (34 mg), useful silane (0.5 ml) and dichloromethane (1 ml), tricorphic acid was added dropwise (0.1 ml) at room temperature. The reaction mixture was worked immediately in the usual way and purified by preparative TLC with silica gel (eluent: 10% methylene / di-chloro), in order to obtain trifluoacetate of (2S) - 1-f enox i -3- [3, 3-bis (4-methoxyphenyl) propyl] amino-2-propanol (21 mg), IR (Pure): 3400 (br), 2933 (m), 1680 (s) , 1604 (m), 1508 (s), 1248 (s), 1203 (m), 1180 (s), 1134 (m), 1036 (m), 829 (m), 756 (m) c "1 NMR ( CDC13, d): 2.3-2.5 (2H, m), 2.7-2.9 (2H, m), 2.9-3.1 (2H, m), 3.74 (6H, s), 3.8-4.0 (3H, m), 4.1-4.3 (lH, m), 6.7-6, 9 (6H, m), 6.95 (2H, t, J = 7.4 Hz), 7.10 (4H, d, J = 8.5 Hz), 7.26 (1H, t, J = 7.9 Hz) MS m / z: 422 (M ++ l ) Example 16 A mixture of (2 S) -3-f enox i-1, 2-p ox i r op an (0.11 g). D-alanine bis (4-methoxy in 1) 1 ml of amine (0.25 g) and methanol (4 ml) was heated under reflux overnight, evaporated and purified by gel column chromatography. of silica, in order to obtain N- ((2S) -2-hydroxy-3-f-enoxopropyl) -D-a-1-ani na [bi s (4-methyl t i i i i i) me t i 1] ami 217 mg). IR (KBr): 3290 (s), 1643 (s), 1606 (m), 1512 (s), 1642 (m), 1250 (s), 1176 (m), 1034 (s), 831 (w), 812 (m), 752 (m) cm "1. NMR (CDC13, d): 1.27 (3H, d, J = 7.2 Hz), 2.66 (1H, dd, J = 3.8 and 12.0 Hz), 2.80 (1H, dd, J = 7, 6 and 12.0 Hz), 153.24 (1H, quartet, J = 6, 9 Hz), 3.74 (3H, s), 3.78 (3H, s), 3.8-4.0 (3H, m), 6.14 (1H, d, J = 8.6 Hz), 6.8-6.3 (6H, m), 6.98 (1H, t, J = 7.3 Hz), 713 (4H, dd, J = 2.0 and 8, 6 Hz), 7.29 (2H, t, J = 7.4 Hz), 7.71 (1H, d, J = 8.6 Hz) MS m / z: 465 (M ++ l) Example 17 To a suspension of lithium aluminum hydride (10 mg) in tetrahydrofuran (0.5 ml), a solution of N - ((2 S) -2-hydroxy-3-25 phenoxypropyl) -D- was added dropwise. alanine [bis (4-methylene oxide) 1) methyl ether (52.4 mg) in tetrahydrofuran, at 0 ° C under nitrogen flow. The reaction mixture was heated under reflux. After 2 hours, additional lithium aluminum hydride (50 mg) was added to the reaction mixture under a stream of nitrogen at 0 ° C. The mixture of The reaction was heated under reflux for 2.5 hours, worked up in the usual manner and purified (preparative TLC, 10% methylene-ethyl acetate) to obtain (2S) -l-phenoxy-3- [ (2R) -1- [[bis (4-methoxyphenyl) methyl] -amino] -2-propyl] amino-2-propanol (31.4 mg). IR (Pure): 3316 (br s), 2931 (m), 1606 (m), 1508 (s), 1458 (m), 1292 (s), 1174 (m), 1036 (s), 820 (m) , 756 (m) cm "1 NMR (CDC13, d): 1.06 (3H, d, J = 6.3 Hz), 2.46 (1H, dd, J = 8.7 and 12.0 Hz) , 2.62 (1H, dd, J = 4.2 and 12.0 Hz), 2.80 (2H, d, J = 4.7 Hz), 3.76 (6H, s), 3.9- 4.1 (3H, m), 4.71 (1H, s), 6.82 (4H, dd, J = 2.0 and 6.7 Hz), 6.9-7.0 (3H, m) , 7.2-7.3 (6H, m) MS m / z: 451 (M ++ l) Example 18 A mixture of (2 R) -2- [4-benzyl-1-ox i -3- (methanesulfonylamino) phenyl] -2- (triethylsiloxy) -1-iodoethane (156 mg), [3, 3-bis ( 4-methoxyphenyl) propyl] amine (75 mg), N, N-diisopropylethylamine (0.19 ml) and tell me 1 to ce t ami da (0.75 ml) was heated at 110 ° C, overnight and worked in the usual manner. The crude product was treated with 4N hydrogen chloride in Ethyl acetate (2 ml) was worked up according to routine methods and purified by preparative TLC (10% methylene-di chlorine orne) in order to obtain (1 R) -1- [4 -be nc i 1 oxy -3- (methanesulfonylamino) phenyl] -2- [3, 3-bis (4-methoxy-phenyl-1) -prop i 1] ami no grade 1 (47 mg). IR (Pure): 3310 (br m), 1608 (w), 1510 (s), 1460 (m), 1329 (m), 1248 (s), 1157 (s), 1120 (s), 1034 (m) , 818 (m), 739 (m) cm "1 NMR (CDC13, d): 2.16 (2H, quartet, J = 7.1 Hz), 2.5-2.7 (3H, m), 2 , 81 (1H, dd, J = 3.6 and 12.2 Hz), 2.90 (3H s), 3.79 (6H, s), 3.95 (1H, t, J = 7.9 Hz ), 4.55 (1H, dd, J = 3.5 and 8.9 Hz), 5.09 (2H, s), 6.81 (4H, d, J = 8.6 Hz), 6.95 (1H, d, J = 8.5 Hz), 7.13 (5H, d, 30 J = 8.6 Hz), 7.35 (5H s), 7.47 (1H, d, J = 2, 0 Hz) MS m / z: 591 (M ++ l) Example 19 The following compound was obtained according to a method similar to that used in Example 18. (IR) -1- [4-Benzyloxy-3 (methanesulfonylamino) phenyl] -2- [[(3RS)] - 1, 1-bis [4- (methoxycarbonylamino) f eni 1] - 3 -bu ti 1] - amino] et ano 1 E xemployment 20 (IR) -1- [4-Benzyloxy-3- (methanesulphonylamino) phenyl] -2- [[3, 3-bis (4-me toxi-phe-1) p ropi 1] ami no] e 1 (35 mg) was hydrogenated by the methods with encionales, in order to obtain (IR) -1- [4-hydroxy-3- (methanesulfonylamino) phenyl] -2 - [[3, 3-bis (4-methoxyphenyl)] -propyl] amino] ethanol (19.3 mg). IR (KBr): 3430 (br m), 1608 (w), 1510 (s), 1319 (m), 1304 (m), 1248 (s), 1153 (m), 1034 (m), 825 (m) cm "1. NMR (CDC13, d): 2.1-2.3 (2H, m), 2.5-2.7 (2H, m), 2.7-2.9 (2H, m), 2.90 (3H, s), 3.74 (6H, s), 3.83 (1H, t, J = 7.8 Hz), 4.5-4.7 (1H, m), 6.79 (5H, d, J = 8.3 Hz), 7.01 (1H, d, J = 8.1 Hz), 7.13 (4H, d, J = 8.4 Hz), 7.13 (1H, br s). MS m / z: 501 (M + + l) EXAMPLE 21 A mixture of (2S) -3- (4-benzyl-1-oxy-3-nitrophenol) -1, 2-epo ipr-opane (197 mg), N-benzyl- [3, 3-bi s (4-methoxymethyl) 1) propy] amine (236 mg) and ethanol (3 ml) was heated under reflux for 12 hours. Iron powder, chloride of Ammonium and water were added to the reaction mixture and heating was continued for 1 hour. The reaction mixture was filtered and worked up in the usual manner in order to obtain (2S) -1- (3-amino-4-benzyloxyphenoxy) -3- [N-benzyl-] 3, 3-bis (4 -me toxi feni 1) -pr opi 1] ami no] -2-propanol (412.7 mg). NMR (CDC13, d): 2.1-2.3 (2H, m), 2.4-2.7 (4H, m), 3.50 (1H, d, J = 14 Hz), 3.75 (6H, s), 3.7-4.0 (5H, m), 5.01 (2H, s), 6.15-6.4 (2H, m), 6.71-6.80 (5H , m), 7.03-7.08 (4 H-7 m), i7.2-7.4 (10H, m). MS m / z: 633 (M ++ l) EXAMPLE 22 The following compounds were obtained according to a method similar to that employed in Example 21. (1) (2 S) -1- (3-Amino-4-benzyloxyphenoxy) -3- [N-benzyl] - [4, 4-bis (4-methoxyphenyl) butyl] amino] -2-pr opane 1 NMR (CDCI3, d): 1.45 (2H, quintet, J = 7.5 Hz), 193 (2H, quintet), 2.3-2.6 (4H, m), 3.44 (1H, d, J = 13.5 Hz), 3.69-4.1 (4H, m ), 3.76 (6H, s), .00 (2H, s), 6.17 (1H, dd, J = 2.9 and 8.8 Hz), 6.31 (1H, d, J = 2.8 Hz), 6.73 (1H, d, J = 8.8 Hz), 6.79 (4H, d, J = 8.7 Hz), 7,) 7 ( 4H, d, J = 7.7 Hz), 7.2- 7.4 (10H, m) MS m / z: 647 (M ++ l) (2) (lRS) -l- (3-Amino-4-benzyloxyphenyl) -2- [N-benzyl- [4, 4] bis (4-methoxy-phenyl) butyl] amino] ethanol "NMR (CDC13, d): 1.4-1.6 (2H, m), 1.8-2.1 (2H, m), 2.4-2.7 (4H, m), 3.41 (1H, d, J = 13.5 Hz), 3.76 (6H, s), 3.7-3, 9 (2H, m), 4.51 (lH, t), 5.05 (2H, s), 6.50-6.65 (2H, m), 6.75-6.85 (5H, m) , 7.05-7.15 (4H,), 7.2-7.5 (10H, m). MS m / z: 617 (M ++ l). (3) (2S) -l-Phenoxy-3- [[3, 3-bis (4-ethoxyphenyl) propyl] -amino] -2-propanol IR (Pure): 3305 (br m), 1604 (m), 1510 (s), 1392 (w), 1300 (w), 1246 (s), 1176 (m), 1047 (s), 822 (m), 756 (m) cm "1. NMR (MeOH-d6, b) ): 1.34 (6H, t, J = 7.0 Hz), 2.2-2.4 (2H, m), 2.6-2.9 (4H, m), 2.97 (4H, quartet, J = 7.0 Hz), 3.9-4.1 ( 4H, m), 6.80 (4H, d, J = 8.6? Z), 6.89-7.0 (3H, m), 7.14 (4H, d, J = 8.6 Hz), 7.26 (2H, t, J = 7, 9 Hz) MS m / z: 450 (M ++ l).

Example 23 To a mixture of (2S) - 1 - (3-ami-4-benzyloxyphenoxy) -3- [N-benzyl- [3, 3-bis (4- I t ox if in i 1) pr op i 1] ami no] - 2-pr op 1 (59 rng), pyridine (0.1 ml) and dichloromethane (1 ml), methanesulfonyl chloride (27 μl) was added ) at 0 ° C and stirred for 30 minutes. The reaction mixture was worked in the usual way. The crude product was hydrogenated in the customary manner, to obtain (2S) -1- [4-hydroxy-3- (methanesulfonylamino) phenoxy] -3- [[3, 3-bis (4-methoxyphenyl) -propyl) ] amino] -2-propanol (17.2 mg). IR (KBr): 3440 (br s), 1610 (w), 1510 (s), 1460 (m), 1325 (m), 1248 (s), 1176 (m), 1151 (m), 1115 (w) , 1034 (m), 816 (m) cm "1. NMR (MeOH-d, d): 2.1-2.3 (2H,), 2.5-2.8 (4H, m), 2, 91 (3H, s), 3.74 (6H, s), 3.8-4.1 (4H, m), 6.6-6.7 (1H, m), 6.7-6.9 ( 5H, m), 6.97 (1H, d, J = 2.7 Hz), 7.1-7.2 (4H, m) MS m / z: 531 (M + + l).

Example 24 The following compounds were obtained according to a method similar to that used in Example 23. (1) (IR) -1- [4-Hydroxy-3- (methanesulfonylamino) phenyl] -2- [ [3, 3-bis [4 - [(methoxycarbonyl) amino] phenyl] propyl] -amino] ethanol MS m / z: 587 (M ++ 1) (2) (2S) -1- [(4-Hydroxy-3- (methanesulfonylamino) phenoxy] -3- [[3, 3-bis [4- [(methoxycarbonyl (amino] phenyl] propyl] amino-2-propanol MS m / z: 617 (M ++ 1) (3) (2S) -1- [4-Hydroxy-3- (methanesulfonylamino) phenoxy] -3- [4 , 4-bis (4-methoxyphenyl) butyl] amino-2-propanol IR (KBr): 3480 (br m), 1612 (m), 1512 (s), 1460 (m), 1321 (w), 1248 (s) ), 1178 (m), 1113 (m), 1034 (m), 826 (m) cm "1 NMR (MeOH-d4, d): 1.4-1.6 (2H, m), 1.9- 2,1 (2H, m), 2.6-2.8 (4H, m), 2.89 (3H, s), 3.73 (6H, s), 3.8-4.1 (4H, m), 6.61 (1H, dd, J = 2.9 and 8.8 Hz), 6.76 (1H, d, J = 8.5 Hz), 6.80 (4H, d, J = 8.6 Hz), 6.96 (1H, d, J = 2.9 Hz), 7.13 (4H, d, J = 8.6 Hz) MS m / z: 545 (M ++ l). (4) (1RS) -1- [4-Hydroxy-3- (methanesulfonylamino) phenyl] -2- [[4,4- bis (4-methoxyphenyl) butyl] amino] ethanol IR (KBr): 3420 (br m ), 1560 (), 1512 (s), 1321 (m), 1248 (s), 1153 (m), 1113 (w), 1034 (m), 817 (m) cm "1 NMR (MeOH-d4, d ): 1.4-1.7 (2H, m), 1.9-2.1 (2H, m), 2.7-2.9 (4H, m), 2.90 (3H, s), 3.73 (6H, s), 3.7-3.9 (1H, m), 4.6-4.8 (1H, m), 6.81 (4H, d, J = 8.7 Hz), 6.85 (1H, m), 7.05 (lH, m), 7.14 (4H, d, J = 8.6 Hz), 7.34 (1H, s) MS m / z: 515 (M ++ l) Example 25 To a solution of (2 S) -1-phenoxy i-3 - [N-benzyl- [3, 3-bis-4-methoxy-enyl) -propyl] -amino] -2-propanol (47 mg) and dichloromethane (1 ml) ), a solution of bromo-di c 1 bromide bromide not 1M was added (0.28 ml), at -78 ° C. The reaction mixture was stirred 0 ° C, for 50 minutes and worked in the usual way, in order to obtain (2 S) - 1 - f enox i - 3 - [N-benzyl- [3, 3-bis (4-hydroxy-enyl) propyl) ] amino] -2-propanol (44 mg). MS m / z: 484 (M ++ l) Example 26 To a mixture of (2 S) -1-phenoxy-3 - [N-benzyl] - [3, 3-bis (4-hydroxyphenyl) propyl] amino] -2-propanol (40 mg), N, N - di isopr op i le lamina (43 μl) and dichloromethane (1 ml), trif 1 anomead trifluoride anhydride (31 μl) was added at -78 ° C. The reaction mixture was worked in the usual way, A mixture of the crude product obtained, palladium acetate (5.6 mg), 1,3-dihydroxyphosphine) pr opane (10.2 mg), triethylamine (46 μl), N, N-dimethylformamide (1 ml) ) and methanol (0.5 ml) was stirred at 100 ° C, under an atmosphere of carbon monoxide (1 atm) for 3.5 hours, worked in the usual way and purified by preparative TLC (hexane: a ethyl acetate = 3: 1), in order to obtain (2S) -l-phenoxy-3- [N-benzyl- [3, 3-bis [4- (methoxycarbonyl) phenyl] propyl] amino] -2-propanol (2 lmg). MS m / z: 568 (M + + l) E nge 27 N- [S - [(2S) -3- [N-Benzyl- [(1RS) -3, 3-bis (4-hydroxyphenyl) -l-methylpropyl] amino] -2-hydroxypropoxy] -2-benzyloxyphenyl] -methanesulfonamide (120 mg) and 10% palladium on activated carbon (50% moisture, 30 mg) in methanol (10 ml) was stirred at room temperature, in the presence of hydrogen at atmospheric pressure for 3 hours and filtered. The filtrate was evaporated in vacuo and treated with 4N hydrogen chloride in ethyl acetate to obtain N- [5 - [(2 S) -3 - [[(1 RS) -3,3-bis (4-) hydrochloride hydroxyphenyl) -l-methylpropyl] amino] -2- hydroxypropoxy] -2-hydroxyphenyl] methanesulfonamide (50 mg). MS m / z: 516 (M ++ l) (free) EXAMPLE 28 The following compound was obtained according to a method similar to that used in the E j emp lo 27. N - [5 - [(2 S) - 3 - [[(1 RS) - 3, 3 Hydrochloride -Bis (4-methoxyphenyl) -l-methylpropyl] amino] -2-hydroxypropoxy] -2-hydroxyphenyl] methanesulfonamide. MS m / z: 544 (M ++ l) (free) Example 29 (2S) -l-f-enoxy-3- [N-benzyl- [3, 3-bis [- (imethoxycarbonyl) -phenyl] propyl] amino] -2-propanol (14 mg) was treated with sodium hydroxide according to the routine methodology and hydrogenated in the customary manner, so as to obtain (2S) -1-f-enoxy-3 - [3, 3-bis (4-ac rboxi f eni 1) pr op i 1] ami no-2-pr opane 1 (12 mg). MS m / z: 450 (M ++ l) E j is 30 A mixture of (2 S) - 3 - f enoxy - 1,2 epoxypropane (0.36 mg), - b e n c i 1 - [3, 3 - b i s [4 [(me t oxi ca rboni 1 o) ami no] f eni 1] prop i 1 - amine (0.97 g) and ethanol (10 ml) was heated under reflux for 12 hours and cooled to room temperature. To the reaction mixture, 10% palladium on charcoal (50% moisture, 0.4 g), 4N hydrogen chloride in 1,4-dioxane (1.1 ml) and methanol (5 ml) were incorporated. The mixture was stirred under hydrogen (1 atm), for 3.5 hours, filtered, diluted with ethyl acetate, neutralized with washes with aqueous sodium bicarbonate and the organic layer was evaporated. The crude product was purified by column chromatography with silica gel (di cl or orne: me t anol: a concentrated ammoniacal guage = 20: 1: 0.05) in order to obtain (2 S) - 1 - f in ox i - 3 - [[3, 3 -bis [4- [(methoxycarbonyl) amino] phenyl] propyl] amino] -2-propanol, which was converted to the corresponding hydrochloride salt (0.71 g) in a similar manner. IR (KBr): 3400 (br m), 1711 (s), 1599 (m), 1537 (s), 1317 (m), 1238 (s), 1072 (m), 758 (m) cm "1 NMR ( MeOH-d4, d): 2.3-2.5 (2H, m), 2.9-3.3 (4H, m), 3.65 (3H, s), 3.71 (3H, s), 3, 9-4.00 (3H, m), 4.1-4.3 (1H, m), 6.91-6, 98 (3H, m), 7.18-7.39 (10H, m) MS m / z: 508 (M ++ l) (free) EXAMPLE 31 The following compound was obtained according to a method similar to that used in E j lo lo 30. (2S) -1- (4-Hydroxyphenoxy) -3- [(3RS) -1, 1-bis ( 4-methoxyphenyl) -3-butyl] amino-2-propanol MS m / z: 452 (M ++ l) Example 32 The following compound was obtained according to a method similar to that used in preparation 16. (2S) -l-Phenoxy-3- [N-benzyl- [(3RS) -1, 1-bis (4- aminophenyl) -l-hydroxy-3-butyl] amino] -2-propanol MS m / z: 512 (M + + l) Example 33 To a mixture of (2S) -1-phenoxy-3 - [N-benzyl] - [(3RS) -1, 1-bis (4-aminophenyl) -l-hydroxy-3-bu ti 1 ] ami no] -2-propanol (100 mg), pyridine (48 μl) and dichloromethane (2 ml), methyl chlorocarbonate (33 μl) was added at 0 ° C. The reaction mixture was worked in the usual way, in order to obtain (2S) -l-phenoxy-3- [N-benzyl- [(3RS) -1,1-bis [4- [(methoxycarbonyl) -amino] phenyl] -l-hydroxy-3- useful] amino] -2-propanol (125 mg). MS m / z: 628 (M ++ l) EXAMPLE 34 The following compound was obtained according to a method similar to that used in Example 33. (2S) -l-Phenoxy-3- [N-benzyl- [(3RS) -1, 1-bis. [4- [N-methyl- (methoxy-carbonyl) amino] phenyl] -l-hydroxy-3-butyl] amino] -2-propanol MS m / z: 656 (M ++ l) Example 35 (2S) -l-Phenoxy-3- [N-benzyl- [(3RS) -1,1-bis [4- [(methoxy-carbonyl) amino] phenyl] -l-hydroxy-3-bu ti 1] amino] -2-pr opane 1 (99 mg) was hydrogenated according to routine methodology, in order to obtain (2S) -lf-enoxy-3- [(3RS) -1, 1-bis [4- ( methoxycarbonyl) amino] -phenyl] -3-butyl] amino-2-propanol (58 mg). MS m / z: 522 (M ++ l) Example 36 The following compounds were obtained according to a method similar to that used in Preparation 18. (1) (2 S) -1-Phenoxy-3 - [(3 RS) 1,1-bis [4- [(ethoxycarbonyl) -amino] phenyl] -3-butyl] amino-2 hydrochloride -propanol. MS m / z: 550 (M ++ 1) (free). (2) (2 S) -1-Fe n ox i -3 - [(13 RS) 1, 1-bis [4- [(trifluoacetyl) -amino] phenyl] -l-hydroxy-3-butyl hydrochloride] amino-2-propanol. MS m / z: 614 (M + + 1) (free). (3) (2S) -l-Phenoxy-3- [(3RS) -1,1-bis [4 (propionylamino (-phenyl] -3-butyl] amino-2-propanol. MS m / z: 518 (M + + l) Example 37 To a mixture of (2 S) -1-phenoxy-3 - [N-benzyl 1 - [(3RS) -1, 1-bis (4-aminophenyl) -l-hydroxy-3-bu ti 1] ami no] - 2-pr opane 1 (120 mg), acetic acid (13 ml) and water (10.6 ml), potassium cyanate was added (77 mg). The reaction mixture was worked in the usual manner, in order to obtain (2S) -1-f-enoxyl-3 - [N-benzyl- [(3RS) -1, 1-bis [4-ureidophenyl] -l -hydroxy-3-bu t yl] ami no] -2-pr opane 1 (65 mg). MS m / z: 598 (M ++ l) Example 38 Formic acid (650 μl) and acetic anhydride (540 μl) were mixed, starting at room temperature, for 30 minutes. The mixture was added to a solution of (2S) -1-f-enox i -3- [N-benzyl- [(3RS) -1, 1-bis (4-aminophenyl) -l-hydroxy-3-butyl] -amino] -2-propanol (325 mg) in dichloromethane (2 ml) at 0 ° C, warmed to room temperature and worked in the usual manner. The crude product was stirred with potassium carbonate (0.62 g) in methanol (4 ml) at room temperature, for 4 hours and worked in the usual manner in order to obtain (2S) -l-phenoxy-3- [N-benzyl- [(3RS) -1, 1-bis [4- (iformylamino) phenyl] -l-hydroxy-3-butyl] amino] -2-propanol (342.4 mg). MS m / z: 568 (M + + l) Example 39 To a mixture of lithium aluminum hydride (0.1 g) and tetrahydrofuran (1 ml), a solution of (2 S) -1-phenoxy-3 - [N-benz i 1 - [( 3 RS) -1,1 -bis [4 - (p-phenylamino) phenyl] -l-hydroxy-3-butyl] amino] -2-propanol (280 mg) in tetrahydrofuran (2 ml) by dripping at 0 ° C. . The reaction mixture was stirred for 2.5 hours and worked in the usual manner in order to obtain (2S) -1-f-enoxyl i-3 - [N-benz i 1 - [(3 RS) -1, 1 - bis [4- (methylamino) phenyl] -l-hydroxy-3-butyl] amino] -2-propanol (273 mg). MS m / z: 598 (M + + l) Example 40 (2S) -lf-enoxy-3- [(3RS) -1,1-bis [4 - [N-methyl- (methoxy-carbonyl) amino] phenyl] -l-hydroxy-3-bu ti 1 was obtained ] ami no - 2 -pr opanol (30 mg) from (2S) -1-phenoxy-3- [N-benzyl- [(3RS) -1, 1-bis [4- [N-me til- ( methoxy-carbonyl) amino] -phenyl] -l-hydroxy-3-bu ti 1] amino] -2-propanol (60 mg), by the usual hydrogenation. MS m / z: 566 (M ++ l) Example 41 (IR) -1- [4-Hydroxy-3- (methanesulfonylamino) phenyl] -2- [[(3RS) -1,1-bis [4 - [(methoxycarbonyl) amino] phenyl] -3-butyl] amino] ethanol (4.3 mg) by hydrogenation, according to the routine methodology. MS m / z: 601 (M ++ l) Example 42 The following compound was obtained according to a method similar to that used in the E j lo lo 41. (2R) -3- [4-Hydroxy-3- (methanesulfonylamino) phenyl] -1- [(3RS) -1, 1-bis (4-me toxy-phenyl-1) -3-bu ti 1] ami no-2-propanol (5.0 mg MS m / z: 529 (M ++ l) Example 43 A mixture of (R) - (- benzyl-1-oxy-3-nitrophenyl) oxirane (34.4 mg), N-benzyl- [3, 3-bis [4- (me t ox i ca rb on i 1 ami no) f eni 1] -pr op i 1] amine (56.7 mg) and ethanol (2 ml) was heated under reflux for 12 hours. Powdered iron, ammonium chloride and water were incorporated into the reaction mixture and heating continued for one hour. The reaction mixture was filtered and worked up according to the routine methodology, in order to obtain (IR) -1- (3 -ami no-4-benzyloxyphenyl) -2- [N-benzyl- [3, 3-bis] [4- [(methoxy-carbonyl) amino] phenyl] propyl] amino] ethanol crude (111.7 mg). MS m / z: 689 (M + + l) The following compound was obtained according to a method similar to that used in Example 43. (2R) -1- (3-Amino-4-benzyloxyphenoxy) -3- [N-benzyl- [3, 3-bis [4- [(methoxycarbonyl) amino] phenyl] propyl] amino] -2-propanol MS m / z: 719 E xample 45 Under nitrogen, to a solution of 4,4-bi s (4-methoxyf eni 1) - 2-bu tonane (187 mg) and (IR) -2-a ino- 1 - ( 2-methylpyridin-6-yl) ethanol (100 mg) prepared from 6-methyl-di-din-2-carboxy-1-dehydrogenide and 1-cyanuryl ether, catalysed with zinc iodide , followed by the reduction with lithium aluminum hydride, in 1, 2-di Cl ormeme (10 ml), tri-acetyl-bor or sodium hydride (257 mg) was added at room temperature and the mixture was stirred at the same temperature, for 24 hours. The resulting mixture was poured into a saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was treated with 4N hydrogen chloride, in 1,4-dioxane, to obtain (1 RS) -2 - [[(1 RS) -3,3-bis (4-methoxyphenyl) -1-methyl) dihydrochloride. -propyl] -amino] -1- (6-methyl-pyridin-2-yl) ethanol (140 mg).

MS m / z: 421 (M ++ l) (free) Example 46 Under nitrogen, a solution of (2S) -3- [4-benzyloxy-3- (methanesulfonylamino) phenoxy] -1,2-epoxypropane (198 mg) and N-benzyl 1 - [(1 RS) -3 3 -bis (4 -hi-dr-oxy-f-1) -1-methyl-1-yl] opy] amine (200 mg) in methanol (20 ml) was refluxed for 18 hours. The resulting mixture was poured into a saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was chromatographed (hexane-ethyl acetate) on silica gel to obtain N- [5 - [(2 S) -3- [N-benzyl] - [(1 RS) -3, 3-bis (4-hydroxyphenyl) -l-methylpropyl] amino] -2-hydroxypropoxy] -2- (benzyloxy) phenyl] methanesulfonamide (120 mg). MS m / z: 696 (M + + l).

Example 47 Under nitrogen, to a solution of (2S) -3- [4-benzyloxy-3- (methanesulfonylamino) phenoxy] -1,2-epoxypropane (200 mg) and N -ben cy 1 - [(1 RS) -3 3-bis (4 I t oxi f eni 1) - 1 -me ti lpr opi 1] amine (163 mg) in dichloromethane (10 ml) was added ^ trif 1 uome tansu 1 phytase of ytterbium (III) (1.0 g) at room temperature and the mixture was stirred at the same temperature, for 3 hours. The resulting mixture was poured into an aqueous saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and evaporated in vacuo. The residue was subjected to chromatography (hexane-ethyl acetate) on silica gel to obtain N- [5- [(2S) -3- [N-benzyl- [(1RS) -3, 3-bis (4- methoxyphenyl) -l-methylpropyl] amino] -2-hydroxypropoxy] -2 - (benzyl 1 oxy) f eni 1] me t an s ul phonamide (50 mg). MS m / z: 724 (M + + l) EXAMPLE 48 Under nitrogen, to a solution of N-benzyl- [3, 3-bis (4-hydroxyphenyl) -l-methylpropyl] amine (300 mg) and loxylinose (130 mg) in a mixture of ethyl acetate (5 ml) and tetrahydrofuran (5 ml) was added triforium 1 to ytterium (III) (110 mg) at room temperature and the mixture was stirred at the same temperature for 96 hours. The resulting mixture was poured into aqueous sodium bicarbonate and saturated and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (c 1 oroform: metal 1 = 20: 1) in order to obtain 1 - [N -b in C 1 - [3, 3-bis (4 - hi dr ox if in i 1) -1 -me ti lpr opi 1] ami no] - 4 - f eni 1 -2 -bu t anol (240 mg). NMR (CDC13, d): 0.95-1.10 (3H, m), 1.45-2.9 (9H, m), 3.2-3.75 (3H, m), 3.75- 3, 9 (1H, m), 6.55-6.8 (4H, m), 6.85-7.3 (14H, m) Example 49 The following compound was obtained according to a method similar to that used in Example 48. (2S) -1- [N-Benzyl- [(1RS) -3, 3-bis (4-hydroxyphenyl) -l-methylpropyl] amino] -3- (phenylthio) -2-propanol NMR (CDCl 3, d): 0.85-1.1 (3H, m), 1.7-3.1 (7H, m), 3.3-3.75 (3H, m), 3.75-3.9 (1H, m), 6.55-6.75 (4H, m), 6.8-7.25 (14H, m ) Example 50 Under nitrogen, to a solution of N- [5 [(IR) -2- [N-benzyl- [(1RS) -3, 3-bis (4-methoxy-enyl) -1- methylpropyl] amino] -1- (triethylsilyloxy) ethyl] -2- (benzyl-1-oxy) pheny1] me tan -su 1 phonamide (221 mg), in tetrahydrofuran (3 ml) were added acetic acid (63 μl) and tetrabutylammonium fluoride (solution in 1M tetrahydrofuran, 0.68 ml) at room temperature and the mixture was stirred at the same temperature during 4.5 hours The resulting mixture was poured saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (hexane: ethyl acetate = 2: 1) to obtain N- [5- [(IR) -2- [N-benzyl- [(1RS) -3, 3-bis (4-methoxy-enyl)] -l-methylpropyl] amino] -1-hydroxyethyl] -2- (benzyl-1-oxy) pheny1] me tansul-onamide (164 mg). NMR (CDC13, d): 0.95-1.1 (3H, m), 1.7-2.85 (5H, m), 2.88 (3H, m), 3.35-4.05 ( 8H, m), 4.25-4.5 (1H, m), 5.08 (2H, m), 6.7-7.5, 121H, m) Example 51 A mixture of N- [5 - [(IR) -2 - [N-benz 1 - [(1RS) -3,3-bis (4-methoxyphenyl) -l-methylpropyl] amino] -1-hydroxyethyl] -2- (benzyloxy) phenyl] methansulfonamide (149 mg) and palladium on 10% activated carbon (50%) of moisture, 50 mg) in methanol (5 ml) was stirred at room temperature in the presence of hydrogen, at atmospheric pressure for 6 hours. After filtration, the filtrate was evaporated in vacuo, followed by treatment with 4N hydrogen chloride in ethyl acetate, in order to obtain N- [5- [(IR) -2- [(1RS)] hydrochloride -3,3-bis (4-methoxyphenyl) -1-methylpropyl] -amino] -1-hydroxyethyl] -2-hydroxy-phenyl] -me-sulphonamide (90 mg). NMR (DMSO-de, d): 1.1-1.35 (3H, m), 1.9-2.2 (1H, m), 2.55-3.1 (7H, m), 3, 70 (6H, m), 3.95-4.1 (1H, m), 4.7-4.9 (1H, m), 6.8-7.4 (11H, m) Example 52 The following compounds were obtained according to a method similar to that used in Example 51. (1) 1 - [3, 3-Bi (4-hydroxyphenyl) -l-methylpropyl] amino hydrochloride -4-phenyl-2-butanol NMR (CD3OD, d): 1.1-1.5 (3H, m), 1.7-1.9 (2H, m), 1.95-2.2 (1H, m), 2.45-3.2 (6H, m), 3.6-4.0 (1H, m), 6.5-6 , 8 (4H, m), 7.0-7.35 (9H, m) (2) (2 S) - 1 - B Hydrochloride encloses its 1 f on i 1 -3- [(1RS) -3 , 3-bis (4-hydroxy-f-enyl) -1-me ti lpr opi 1] amino-2-propanol NMR (CD3OD, d): 1.25-1.4 (3H, m), 1.95-2.2. (1H,), 2.45-2.7 (1H, m), 2.9-3.55 (5H, m), 3.85-4.0 (1H, m), 4.25-4, 4 (1H, m), 6.65-6.85 (4H, m), 7.05-7.2 (4H, m), 7.6-7.8 (3H, m), 7.95-8.05 (2H, m). (3) (2 S) -1-Phenoxy-3 - [(3 RS) -1,1-bis (4-ureidophenyl) -3-butyl] amino-2-propanol hydrochloride MS m / z: 492 (M ++ l) (free) Example 53 Under nitrogen, a solution of [(lS) -3,3-bi s (4-methoxyf eni 1) - 1 -methylprop i] amine (0.55 g), N- [2-benzyloxy-5- [(IR) -2-iodo-l- (triethylsilyloxy) ethyl] phenyl] -methansulfonamide (1.1 g) and N, N-di is op r op il eti lamina (1 , 4 ml) in N, N-dime ti 1 a ce t ami da (5 ml), was stirred at 110 ° C for 24 hours. The resulting mixture was poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed successively with water and brine, dried over anhydrous sodium sulfate and evaporated in vacuo. Under nitrogen, to the residue in ethyl acetate (10 ml) was added 4N hydrogen chloride in ethyl acetate (2 ml) at 5 ° C and the mixture was stirred at room temperature for 45 minutes. The resulting mixture was poured into saturated and aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (gold form: grade 1 = 50: 1 to 20: 1) to obtain N- [2-benzyloxy-5- [(IR) -2- [ (ÍS) -3, 3-bis (4-methoxyphenyl) -l-methylpropyl] -amino-1-hi dr oxy and il] f in i 1] me tan - su 1 f on ami da (0.65 g) . NMR (CDC13, d): 1.09 (3H, d, J = 6.3 Hz), 1.85-2.3 (2H, m), 2.35-2.6 (2H, m), 2.9-3.2 (4H, m), 3.76 (6H, s), 4, 0-4.1 (1H, m), 4.45-4.6 (1H, m), 5.10 (2H, m), 6.82 (4H, d, J = 8.1 Hz), 6 , 96 (1H, d, J = 8.5 Hz), 7.1-7.2 (5H, m), 7.35-7.5 (6H, m) Example 54 The following compounds were obtained according to a method similar to that used in E j empl o 53. (1) N- [2-Benzyloxy-5- [(IR) -2- [(IR) -2 - [(IR) - 3, 3-bis (4-methoxyphenyl) -1-methyl-propyl] amino-1-hydroxyethyl] phenyl] -methanesulfonamide NMR (CDCl 3, d): 1.08 (3H, d, J = 6.2 Hz), 1.9-2.2 (2H, m), 2.5-2.85 (3H, m), 2.90 (3H, s), 3.76 (6H, s), 4.03 (1H, t, J = 8.2 Hz), 4.47 (1H, dd, J = 3.6 and 8.5 Hz), 5.10 (2H, s), 6.8-6.9 (4H, m), 6.96 (1H, d, J = 8.5 Hz ), 7.1-7.2 (5H, m), 7.35-7.5 (6H, m) (2) N- [2-Benzyloxy-5- [(1RS) -2- [(1RS) -3, 3-bis (4-hydroxy-f-enyl) -l-methylpropyl] amino-1-hydroxyethyl] phenyl] -methane-sulfonamide NMR (DMSO-de, d): 1.0-1.1 (3H, m), 1.7-1.95 (1H, m), 2.1-2.85 (4H, m), 2.90 (3H, s), 3.8-3.95 (1H, m) , 4.5-4.6 (1H, m), 5.17 (2H, s), 6.6-6.75 (4H, m), 6.95-7.2 (6H, m), 7 , 25-7.6 (6H, m) Example 55 A mixture of N- [2- (benzyloxy) -5- [(IR) -2- [(SS) -3,3-bis (4-methoxyphenyl) -l-methylpropyl] amino-1-hydrox ox ieti 1] fe ni 1] -me t an - its 1 f on ami da (620 mg) and palladium on activated charcoal at 10% (50% moisture, 300 mg) in methanol (10 ml) was stirred at room temperature, in the presence of hydrogen at an atmospheric pressure for 7.5 hours. After filtration, the filtrate was evaporated in vacuo. The residue was purified by column chromatography on silica gel (1: 1: 1: 20: 1 to 10: 1), followed by treatment with 4N hydrogen chloride in ethyl acetate, obtain N- [5 - [(1 R) -2 - [(1 S) -3,3-bis (4 - hydrochloride methoxyphenyl) -l-methylpropyl] amino-1-hydroxy-ethyl] -2-hydr-oxy-phen-1] metan-1-ammonide (290 mg). NMR (DMSO-de, d): 1.15-1.4 (3H, m), 1.85-2.2 (1H, m), 2.4-3.2 (7H, m), 3, 70 (6H, s), 3.95-4.1 (1H, m), 4.7-4.9 (1H, m), 6.7-7.4 (11H, m) Example 56 The following compounds were obtained according to a method similar to that used in Example 54. (1) N - [5 - [(1 R) -2 - [(1 R) - 3 Hydrochloride , 3-Bis (4-methoxyphenyl) -l-methylpropyl] amino-1-hydroxyethyl] -2-hydroxy-enyl] -methanesulfonamide. NMR (DMSO-d6, d): 1.15-1.4 (3H, m), 1.9-2.15 (1H, m), 2.4-3.15 (7H, m), 3, 70 (6H, m), 3.95-4.1 (1H, m), 4.75-4.9 (lH, m), 6.8-7.4 (11H, m) (2) Hydrochloride N - [5 - [(1 R) -2 - [[3, 3-Bis (4-hydroxyphenyl) -l-methylpropyl] amino] -1-hydroxyethyl] -2-hydroxyphenyl] -methanesulfonamide. NMR (DMSO-d6, d): 1.15-1.3 (3H, m), 1.85-2.1 (1H, m), 2.55-3.2 (7H, m), 3.8-4.0 (lH, m), 4.7-4.9 (1H, m), 6.6-6 , 75 (4H, m), 6.9-7.3 (7H, m) (3) (2S) -l- (6-aminopyridin-3-yloxy) -3- [[(1RS) -3 trichlorohydrate] 3-bis (4- methoxyphenyl) -l-methylpropyl] amino] -2-propanol, starting with the objective compound of Example 57. NMR (DMSO-de, d): 1.05-1.4 (3H, m), 1.9-2 , 2 (1H, m), 2.5-3.2 (4H, m), 3.55-3.85 (7H, m), 3.85-4.3 (3H, m), 6, 9 -7.4 (9H, m), 7.5-7.9 (2H, m) Example 57 A mixture of [3, 3-bis (4-methoxy-enyl) -1-me ti-lpr-opi 1] amine and (2S) -3- [2- (benzyloxycarbonylamino) pyridin-5-yloxy] -1 2-epoxypropane (98 mg) in methanol (5 ml) was refluxed for 19 hours. After removing the solvent in vacuo, the residue was purified by column chromatography on silica gel (chloroform methanol = 30: 1 to 20: 1), in order to obtain benzyl-acid ester [5 - [ (2 S) - 3 - [(1 RS) - 3, 3-bis (4-methoxyphenyl) -l-methylpropyl] amino-2-hydroxypropyl] pyridine n-2 - i 1] camobrate (110 mg). NMR (CDC13, d): 1.1-1.2 (3H, m), 1.7-2.3 (2H, m), 2.45-2.6 (2H, m), 2.7- 2.75 (lH, m), 3.76 (6H, s), 3.85-3, 95 (3H, m), 4.0-4.1 (1H, m), 5.22 (2H, s), 6.8 (4H, d, J = 8.6 Hz), 7.1-7.45 (10H, m), 7, 9-7, 95 (2H, m).

Example 58 To a solution of (2S) -1- [N-benzyl] - [(1-RS) -3,3-bis (4-hydroxyphenyl) -l-methylpropyl] amino] -3-f eni 1 thio -2- propane 1 (300 mg) in methanol (10 ml) was added OXONE® (potassium peroxymonosulfate) (710 mg) in water (2 ml), at room temperature and the mixture was stirred at the same temperature, for 4 hours. The resulting mixture was poured into a mixture of ethyl acetate and water, and basified with saturated aqueous sodium bicarbonate. After separation, the organic layer was washed with brine, dried over anhydrous magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (cl oroform: methanol = 20: 1), so as to obtain (2S) -1-benz enesu 1 f on i 1 - 3 - [N - b in cy 1 - [(1RS) -3, 3-bis (4-hydroxyphenyl) -l-methylpropyl] amino] -2-propanol (220 mg). NMR (CDC13, d): 0.9-1.1 (3H, m), 1.75-2.3 (2H, m), 2.35-2.7 (3H, m), 2.9- 3.25 (2H, m), 3.3-4.0 (4H, m), 6.65-6.8 (4H, m), 6.9-7.35 (9H, m), 7, 5-7.7 (3H,), 7.75-7.9 (2H, m) Example 59 A mixture of (2 S) -1-f-enoxy-3 - [N-benzyl] - [3, 3-bis (4-methoxycarbonyl) phenyl] propyl] amino] -2-propanol (103 mg), methanol (2 ml), 1,4-dioxane (2 ml) and an aqueous sodium hydroxide solution (1 ml) was stirred at 50 ° C for 2 hours. The reaction mixture was acidified with 3N hydrochloric acid (1 ml) and worked in a similar manner, in order to obtain (2S) -l-phenoxy-3- [N-benzyl- [3, 3-bis (4- ca rboxi phenyl) prop i 1] ami no] -2-propane 1 (75.1 mg) E xample 60 A mixture of (2 S) -1-phenoxy-3 - [N-benzyl- [3, 3-bis (4-ca rboxi f enyl) pr op i 1] ami no] - 2 -pr opanol (75 mg), di-pheni-1-phosphide azide (96 mg), triethylamine (58 μl), toluene (1 ml) and 1,4-dioxane (1 ml) was stirred at 50 ° C for 0.5 hours and, subsequently, at 100 ° C for a period of 45 minutes. Methanol (1 ml) was added to the reaction mixture and heating continued for 15 hours. The reaction mixture was worked in a routine manner, followed by purification by preparative thin layer chromatography, to obtain (2S) -1-phenoxy-3- [N-benzyl- [3, 3-bis [4- [( methoxycarbonyl) amino] phenyl] propyl] amino] -2-propanol (21.5 mg). MS m / z: 598 (M ++ l) E n gle 61 The (2S) -l-phenoxy-3- [N-benzyl- [3, 3-bis (4- [(methoxy-carbonyl) amino] phenyl] propyl] amino] -2-propanol (18.8 mg) is hydrogenated in a similar manner, in order to obtain (2S) -1-f-enoxy-3 - [[3, 3-bis [4- [(methoxycarbonyl) amino] phenyl] propyl] amino] -2-propanol (8 , 1 mg) IR (KBr): 1710 (s), 1601 (m), 1537 (s), 1315 (w), 1238 (s), 1070 (m) cm "1 NMR (MeOH-d4, d) : 2.2-2.3 (2H, m), 2.6-2.9 (4H, m), 3.72 (6H, s), 3.9-4.1 (4H, m), 6 , 9-7.0 (3H,), 7.2-7.4 (10H, m) MS m / z: 508 (M ++ l)

Claims (10)

1. Compounds derived from aminoalcohols for application as β-adrenergic receptor agonists characterized because they have the f ormu 1 a. wherein A is a heterocyclic or aryl group, each of which may have between 1 and 3 substituents which may be the same or different selected from a group consisting of halogen, hydroxy, amino, lower alkyl, at 1 qu 1 -sulphon 1 amino lower, phenyl-lower alkoxy and phenyl 1 to 1 coxi ca rboni 1 ami no (lower), -X- is a bond, -CH2-, -CH2-CH2-, -NH -CH2-, -0-CH2-, -S-CH2-, -SO-CH2-0-SO2-CH2-, (in which R11 is hydrogen, hydroxy, lower alkoxy or alkoxy) and - (CH2) "- CH = CH- (CM2) n? - or - (CH2) n-C C- (CH2)," - (where -Q- cs -O-, -S-, -SO-, -SO: -, -N-CO-, -CO-N-, R? O R IO -Cl? -CO-N-, -Cl l-CH. -N-, -SO-N-, I I I i • -N-CO, -, -CO- or -N-, p M i K R It) wherein R10 is hydrogen, or lower alkyl and R11 is inner alkyl, R6, R7, R8 and R9, each independently, are hydrogen, hydroxy, lower alkyl, lower alkyl, lower alkoxy, alkoxy inferio r- a 1 qu i 1 o (lower) or aril, which can have 1 and 3 lower alkoxy n, m and k, each independently, e 0 to 6, p e s 0 to 4, q is 1 a 4 y, r is 2 to 7), and (in which i is 0 to 6), R1 is hydrogen or a protective amino group, and R2, R3, R4 and R5, each independently, is hydrogen; lower alkyl; lower alkylthio; lower alkyl sulfonyl; hydroxy; lower alkoxy; amino, lower alkylamino; acylamino; N- (lower alkyl) -acilamino; carboxy; lower alkoxycarbonyl; carbamoyl, optionally substituted with one or two lower alkyl; hydroxy-lower alkyl; lower alkoxy-lower alkyl; N-acylamino-lower alkyl; N- (lower alkyl) -N-acylamino-lower alkyl; carboxy-lower alkyl; lower alkoxycarbonyl-lower alkyl; carbamoyl-lower alkyl, optionally substituted with one or two lower alkyl; or (in which R12 and R13, each of which is in the form is independent, is hydrogen or lower alkyl, or they can be linked to form a lower alkylene chain and j is 0 to 6 and a salt thereof.

2. Compounds according to claim 1, characterized in that A is a pyridyl, indolyl, 2 -oxo-2, 3-3 -di-hi-hi-1-Hb-enzyme-1, each of which may have between 1 and 3 replaces tes - which may be the same or different - selected from a group consisting of hydroxy, amino, lower alkyl, 1 to 1 - s ul foni 1 ami not lower, phenyl-lower alkoxy and phenyl 1 - a 1 coxi-ca rboni 1 amino (lower), -X- is a bond, -CH2-, -CH2-CH2-, -0-CH2 - o- S 02 - CH2- -Y. is -C k 11 (in which R n is hydrogen hydroxy and or where -Q- -Cl 1 -CO-N- O -CH-CH.-N-, where R10 is hydrogen or lower alkyl, and R11 is lower alkyl; R6, R7, R8 and R9, each independently, is hydrogen, lower alkyl or aryl, which may have between 1 and 3 lower alkoxy n, myk, each independently, is 0 to 6, and r is 2 to 7) and (in which 1 is 0 to 6), R1 is hydrogen or ar-lower alkyl; and R2, R3, R4 and R5, each of them independently, is hydrogen; lower alkyl; lower alkyl; lower alkylsulfonyl; hydroxy; lower alkoxy; Not me; lower alkylamino; acylamino; N- (lower alkyl) acylamino; carboxy; or lower alkoxycarbonyl.

3. Compounds according to claim 2, characterized in that A is a pyridyl, indolyl or phenyl, each of which may have between 1 and 3 substituents - which may be the same or different ones selected from a group consisting of hydroxy, amino, lower alkyl, at 1 qi 1-s 1-lower amino, phenylalkoxy (lower) and phenyl-1-alkyloxycarbonyl (lower), -X- is a bond, -CH2-, -CH2-CH2- , -0-CH2-o-S02-CH2-, (in which R11 is hydrogen or hydroxy); Y (where is - (CH2) n- - (CH2) n-Q- -Q- -Cii-CO-N- -CH-CII - N-, where R R1 1 R1"R- is hydrogen lower alkyl, and R 11 is lower alkyl; R6, R7, R8 and R9, each independently, is hydrogen, lower alkyl or phenyl, which may have between 1 and 3 lower alkoxy; n, m and k, each independently, is O a l, and r is 2 a 7); Y (in which i is O to 1), R1 is hydrogen or phenyl-lower alkyl; and R2, R3, R4, and R5 each independently, is hydrogen; lower alkyl; lower alkylthio; lower alkylsulfonyl; hydroxy; lower alkoxy; Not me; lower alkylamino; alkoxy-carbonylamino (lower); alkyl sulfonylamino (lower); lower alkanoylamino; ureido; trifluoroacetylamino; N- (lower alkyl) [(lower alkoxycarbonyl]] amino; carboxy; or lower alkoxycarbonyl.

4. Compound according to the rei indication 3, characterized in that: A is phenyl, each of which may have between 1 and 3 substituents -which may be the same or different- selected from a group consisting of hydroxy, amino, alkyl- lower sulfonylamino and phenyl-lower alkoxy; -X- is a link, - CH 2 -, CH2-CH2-, -O-CH2-0-SO2-CH2-, (in which R is hydrogen or hydroxy) Rβ R8 is - (CH2) n-¿- (CH 2'm-¿- (CHl, 2) 'wk- ", - (C te (wherein R6, R7, R8 and R9, each independently, is hydrogen, lower alkyl or phenyl, which may have between 1 and 3 lower alkoxy; n, myk, each independently, is 0 or 1, and R1 is hydrogen or phenyl-lower alkyl; R2, R3, R4 and R5 each independently, is hydrogen; lower alkyl; lower alkylthio; lower alkylsulfonyl; hydroxy; lower alkoxy; Not me; lower alkylamino; lower alkoxy-carbonylamino; rent- lower onylamino sulf; lower alkanoylamino; ureido; trifluoroacetylamino; N- (lower alkyl) [(lower alkoxycarbonyl]] amino; carboxy; or lower alkoxycarbonyl.

5. Compounds according to claim 4 characterized in that: A is phenyl, each of which may have 1 or 2 substituents - which may be the same or different - selected from a group consisting of hydroxy, amino and alkyl-sulfonylamino; -X- is a bond or -0-CH2-, is -C 11, i *. ' I-I i i; -Z- cs -C-C- I II II R1 is hydrogen; and R2, R3, R4 and R5 each independently is hydrogen; lower alkoxy or 1 coxi-c to rbon i 1 ami, lower.

A compound according to the claim 5, characterized in that it is: (2S) -1- [4-hydroxy-3- (methanesulfonylamino) -phenoxy] -3- [[3, 3-bis (4-methoxyphenyl) propyl] amino] -2-propanol; (IR) -1- [4-Hydryo-3- (methanesulfonylamino) -phenyl] -2- [[3, 3-bis (4-methoxyphenyl) propyl] amino] -ethanol; (2S) -1-phenoxy-3- [[3, 3-bis [4- [(methoxy-carbonyl) amino] -phenyl] propyl] amino] -2-propanol; 0 a salt of the same ones.

7. Process for the preparation of the compounds according to claim 1, characterized salts thereof, because it comprises: (i) Reacting a compound [II] of the f or ul a: ? -X-C'H-? I? [III wherein A and X are defined, according to claim 1, with a compound [III] of the formula; in which Y, Z, R1, R2, R3, R4 and R5, each [III] one of them, are defined according to claim 1, or a salt thereof, in order to obtain a compound [I] of the formula: wherein A, X, Y, Z, R1, R2, R3, R4 and R5, each are defined according to claim 1, or a salt thereof, or (ii) Submit a compound [the ] of the formula: wherein A, X, Y, Z, R2, R3, R4 and R5, each of them, is defined according to claim 1; and R1 is a protective amino group, or a salt thereof, to the elimination reaction of the amino protecting group, in order to obtain a compound [Ib] of the formula ? -X- íi] wherein A, X, Y, Z, R2, R3, R4 and R5, each of them, is defined according to claim 1, or a salt thereof.

8. Pharmaceutical compositions characterized in that it comprises, as an active ingredient, a compound according to claim 1 or a pharmaceutically acceptable salt thereof, in a mixture with pharmaceutically acceptable excipients or carriers.

9. Use of the compounds according to claim 1, or pharmaceutically acceptable salts thereof characterized in that for the manufacture of a medicament.

10. Compounds according to claim 1 or pharmaceutically salts acceptable of them, characterized because they comprise their application as medicines. SUMMARY These are new derivatives of aminoalcohols or the salts thereof, represented by the following formula [I]: in which each symbol is as defined in the specification, or the salts thereof, which exhibit selective non-selective activities of the intestines, anil -ul zero sas, antipacreatitis, lipolytic, an ti - incontinence - urinary and anti-pollakiuria; with the processes that are destined to the preparation of the same ones; with a pharmaceutical composition comprising them; and with a method for the prevention and / or treatment of the diseases indicated in the specification, both in a human being and in animals. In said formula A is a heterocyclic or aryl group, each of which may have between 1 and 3 substituents -which may be the same or d i f e r- entities- selected from a group consisting of in halogen, hydroxy, amino, lower alkyl, lower alkyl sulfonylamino, phenyl-lower alkoxy and phen i 1 to 1 coxi ca rboni 1 ami no (lower), -X- is a bond, -CH2-, -CH2-CH2-, -NH-CH2-0-CH2-, -S-CH2-, -SO-CH2-0-SO2-CH2-, (in which R 1 '1 e s hydrogen, hydroxy, lower alkoxy acyl oxy) and -Z- e - (CH2) p-CH = CH- (CH) ro - (CH2) UC C- (CH2) m- (where -0- cs -0- .S-, -SO-, -SO-, - N-CO-, -CO-N-, -CH-CO-N-, -CI I-CH.-N-, -SO. -N-, 1 1 I l R11 R10 R11 R10 RIO -N-CO, -, -CO- or -N- wherein R10 is hydrogen, or lower alkyl, and R11 is lower alkyl, R6, R7, R8 and R9, each independently, are hydrogen, hydroxy, lower alkyl, lower alkenyl, lower alkoxy, alkoxy in fer ior- to 1 qui 1 o (lower) or aryl, which can have from 1 to 3 lower alkoxy, n, m, and k, each of them independently, is 0 to 6, p is 0 to 4, qes 1 to 4 y, is 7) yy -ZY < is - (CH2) j i « (in which i is 0 6) R is hydrogen or a protective amino group, and R 2, R 3, R 4 and R 5, each independently, is hydrogen; lower alkyl; lower alkylthio; lower alkyl sulfonyl; hydroxy; lower alkoxy; Not me; alkylamino lower; acylamino; N- (lower alkyl) -acilamino; carboxy; lower alkoxycarbonyl; carbamoyl, optionally substituted with one or two lower alkyl; hydroxy-lower alkyl; lower alkoxy-lower alkyl; N-acylamino-lower alkyl; N- (lower alkyl) -N-acylamino-lower alkyl; carboxy-lower alkyl; lower alkoxycarbonyl-lower alkyl; carbamoyl-lower alkyl, optionally substituted with one or two lower alkyl; or (in which R12 and R13, each of them in R12 - (CH2) j -N R13 independently, it is hydrogen or lower alkyl, or R12 and R13 can be linked to form - a lower alkylene chain 'and j is 0 to 6) and a salt thereof.