MXPA98008367A - Derivatives of feniletanolaminotetralincarboxam - Google Patents

Abstract

The present invention relates to a phenylethanolaminotetralincarboxamide derivative represented by the general formula, wherein a represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which can contain an oxygen atom in the ring. The carbon atom marked with (*) represents a carbon atom in configuration (R), configuration (S) or a mixture thereof, and the carbon atom marked with (S) represents a carbon atom in configuration (S), and an pharmaceutically acceptable salt thereof, which has a stimulatory effect of α2-adrenergic receptor with oppressions relieved in the heart, such as, tachycardia and useful as an agent for the prevention of threatened abortion and premature labor, a bronchodilator and an agent for remission of pain and promote the removal of stones in urolithias

Description

DERIVATIVES OF FENILETANOLAMINOTETRALINCARBOXAMIDA TECHNICAL FIELD The present invention relates to novel phenylethanolaminotetraincarboxamide derivatives, which are useful as medicaments. More particularly, the present invention relates to phenylethanolaminotetraincarboxamide derivatives, represented by the general formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which may contain an oxygen atom in the ring; carbon labeled with * represents a carbon atom in configuration (R), configuration (S) or a mixture thereof, and the atom marked with (S) represents a carbon atom in (S) configuration) and pharmaceutically acceptable salts of the same, which have a selective β2-adrenergic receptor stimulating effect with oppressions relieved in the heart, such as tachycardia.

BACKGROUND ART Substituted phenylethanolaminotetraline derivatives have been described, for example, compounds represented by the general formula: (wherein R a represents a hydrogen atom or an ethyl group, and Y represents a hydrogen atom or a chlorine atom), hydrochloride or oxalate thereof, or simple optical isomers thereof and a compound represented by the formula: (wherein the carbon atom marked with (R) represents a carbon atom in the (R) configuration, and the carbon atom marked with (S) represents a carbon atom in (S) configuration, which has antipollakiuria activities and fundamental selective sympathomimetics (see Japanese published patent application (kohyo) No. Hei 6-506676 and Japanese published patent application (kohyo) No. Hei 6-506955). However, the compounds are ß3-adrenergic receptor stimulating agents having an outstanding β3-adrenergic receptor stimulating effect.

Description of the invention The present invention relates to phenylethanolaminotetraincarboxamide derivatives represented by the general formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which may contain an oxygen atom in the ring; carbon marked with * represents a carbon atom in configuration (R), configuration (S), or a mixture thereof, and the carbon atom marked with (S) represents a carbon atom in (S) configuration and salts pharmaceutically acceptable thereof. The present invention relates to a pharmaceutical composition comprising the above phenylethanolaminotetraincarboxamide derivative or a pharmaceutically acceptable salt thereof. The present invention relates to an agent for the prevention of threatened abortion or premature labor, a bronchodilator and an agent for remission of pain and promote the removal of stones in urolithiasis, which comprises as the active ingredient the phenylethanolaminotetraincarboxamide derivative above or a pharmaceutically acceptable salt thereof. The present invention relates to a method for the prevention of threatened abortion and premature labor, the prevention and treatment of diseases associated with bronchiostenosis and obstruction of the respiratory tract, and remission of pain and promotion of stone removal in urolithiasis, which comprises administering the above phenylethanolaminotetraincarboxamide derivative or a pharmaceutically acceptable salt thereof. The present invention relates to the use of the above phenylethanolamiotetraincarboxamide derivative or a pharmaceutically acceptable salt thereof for the manufacture of a pharmaceutical composition for the prevention of threatened abortion and premature labor, the prevention and treatment of diseases associated with bronchiostenosis and obstruction of tracts Respiratory and remission of pain and promotion of stone removal in urolithiasis. Additionally, the present invention relates to the use of the above phenylethanolaminotetralinecarboxamide derivative or a pharmaceutically acceptable salt thereof, as an agent for the prevention of threatened abortion and premature labor, a bronchodilator and an agent for pain remission and promotion of removal. of stones in urolithiasis.

BEST MODE FOR CARRYING OUT THE INVENTION In order to find an excellent β-adrenergic receptor stimulating agent, the inventors of the present invention did extensive studies and found that certain phenylethanolaminotetraincarboxamide derivatives represented by the above general formula (I) have a stimulating effect of potent and selective receptor and is outstandingly useful as a β2-adrenergic receptor stimulating agent, thereby forming the basis of the present invention. Accordingly, the present invention relates to phenylethanolaminotetraincarboxamide derivatives represented by the general formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which may contain an oxygen atom in the ring; carbon labeled with * represents a carbon atom in configuration (R), configuration (S) or a mixture thereof, and the carbon atom marked with (S) represents a carbon atom in (S) configuration and pharmaceutically salts acceptable thereof, which have a stimulating effect of β2-adrenergic receptor with greater selectivity compared to a stimulating effect of ß-adrenergic receptor and with oppressions relieved in the heart, such as tachycardia.

In the compounds represented by the above general formula (I) of the present invention, the term "di (lower alkyl) amino" group means an amino group di-substituted by straight or branched chain alkyl group (s) having 1 to 6 carbon atoms (for example, methyl, ethyl, propyl, isopropyl), such as a dimethylamino group, a diethylamino group, an ethylmethylamino group or the like. Also, the term "lower alkylene group" means a straight chain alkylene group having 1 to 3 carbon atoms, such as a methylene group, an ethylene group or a trimethylene group, and the term "3 to 7 membered alicyclic amino group". which may contain an oxygen atom in the ring "means a 1-pyrrolidinyl group, a piperidino group, a morpholino group or the like. The compounds represented by the above general formula (I) of the present invention can be prepared by the following procedure. For example, the compounds of the present invention can be prepared by subjecting an amine compound represented by the general formula: (wherein R represents a lower alkyl group, and A and the carbon atom marked with (S) have the same meanings as defined above) a? -alkylation using an alkylating agent represented by the general formula: (wherein R ° represents a hydroxy-protective group, and X represents a halogen atom), reducing the resulting compound in the usual manner, removing the hydroxy-protective group as the occasion demands to give a compound represented by the general formula: (wherein R1 represents a hydrogen atom or a hydroxy-protective group, and A, R and the carbon atom marked with (S) have the same meanings as defined above), subjecting the resulting compound to amidation in the usual manner using an amine compound represented by the general formula: BH (V) (wherein B has the same meaning as defined above), and removing the hydroxy-protective group as the occasion demands. The compounds represented by the above general formula (I) of the present invention can also be prepared by subjecting an amine compound represented by the general formula: (wherein A, B and the carbon atom marked with (S) have the same meanings as defined above) a? / - alkylation using an alkylating agent represented by the above general formula (I II), reducing the resulting compound in the usual way and remove the hydroxy-protective group. Additionally, the compounds represented by the above general formula (I) of the present invention can be prepared by allowing a mandelic acid derivative represented by the general formula: (where R ° has the same meaning as defined above) react with an amine compound represented by the formula: (wherein the carbon atom marked with (S) has the same meaning as defined above) in the presence of a condensing agent to give a compound represented by the general formula: (wherein R ° and the carbon atom marked with (S) have the same meanings as defined above), reducing the resulting compound using a reagent, such as borane-dimethylsulfide complex to prepare a compound represented by the general formula: (wherein R ° and the carbon atom marked with (S) have the same meanings as defined above), protect the alcoholic hydroxy group and the amino group with a reagent such as trifluoroacetic anhydride as the occasion demands, subject the compound resulting in O-alkylation using an alkylating agent represented by the general formula: XA-COB (XI) (wherein A, B and X have the same meanings as defined above) and removing the protecting group. The amine compounds represented by the above general formulas (II) and (VI II), which are used as starting materials in the aforementioned production processes, can be prepared according to a method described in a literature or methods analogous to it (eg, Eur. J. Med. Chem., No. 29, pp. 259-267 (1994), a published Japanese patent application (Kokai) No. Hei 3-14548). The compounds represented by the above general formula (I I I), which are used as starting materials in the aforementioned production processes, can be prepared by subjecting a ketone compound represented by the general formula: (wherein R2 represents a hydroxy-protective group suitable for this reaction) to halogenation using a halogenating agent according to a method described in a literature or methods analogous to it (eg, Bull. Chem. Soc. Jpn., Vol. Pp 65, 295-297 (1992), Synthesis, No. 7, pp. 545-546 (1988), Synthesis, No. 12, pp. 1018-1020 (1982)), and convert the hydroxy-protective group of the resulting compound in another hydroxy-protective group as the occasion demands. The amine compounds represented by the above general formula (VI), which are used as starting materials in the aforementioned production process, can be prepared by subjecting a phenol compound represented by the general formula: (wherein R3 represents an amino-protecting group, and the carbon atom marked with (S) has the same meaning as defined above) to O-alkylation using an alkylating agent represented by the above general formula (XI) and then removing the amino-protective group , or by protecting the amino group of a compound represented by the above general formula (II) using an appropriate reagent, converting the resulting compound to a free carboxylic acid or a reactive functional derivative thereof as the occasion demands, subjecting the resulting compound to amidation using an amine compound represented by the above general formula (V), in the presence or absence of a condensing agent and remove the amino-protective group. Among the compounds represented by the above general formula (I) of the present invention, simple isomers can be prepared, for example, by subjecting a mixture of diastereomers obtained by the aforementioned process to fractional recrystallization in the usual manner, or by allowing an optically active mandelic acid derivative, represented by the general formula: (wherein the carbon atom marked with (R) represents a carbon atom in the (R) configuration, and R ° has the same meaning as defined above) or another optically active mandelic acid derivative, represented by the general formula: (wherein R ° and the carbon atom marked with (S) have the same meanings as defined above) react with an amine compound represented by the above formula (VI II), in the presence of a condensing agent to give a simple isomer represented by the general formula: (wherein R °, the carbon atom marked with (R) and the carbon atom marked with (S) have the same meanings as defined above) or another simple isomer represented by the general formula: (wherein R ° and the carbon atoms marked with (S) have the same meanings as defined above), reducing the resulting isomer using a reagent, such as borane-dimethylsulfide complex to prepare a compound represented by the general formula: (wherein R °, the carbon atom marked with (R) and the carbon atom marked with (S) have the same meanings as defined above) or a compound represented by the general formula: (where R °, the carbon atoms marked with (S) have the same meanings as defined above), protect the alcoholic hydroxy group and the amino group, using a reagent such as trifluoroacetic anhydride as the occasion demands, submit the resulting compound to O-alkylation using an alkylating agent represented by the above general formula (XI) and removing the protecting group. Among the compounds represented by the above general formula (I) of the present invention, simple isomers can also be prepared by subjecting a mixture of diastereomer obtained as an intermediate by the above-mentioned process, to column chromatography or fractional recrystallization, to isolate the isomer corresponding simple and then perform the same reaction using said simple isomer. The mandelic acid compounds represented by the above general formulas (VI l), (XIV) and (XV), which are used as starting materials in the aforementioned production processes, for example, can be prepared by allowing a compound of bromine represented by the general formula: (wherein R ° has the same meaning as defined above), which can be obtained according to a method described in a literature or processes analogous to it, react with diethyl oxalate, reduce the resulting phenylglyoxylic acid derivative using a reagent such as sodium borohydride, hydrolyze the ester compound to give a mandelic acid derivative represented by the above general formula (Vi l), and subject the compound to optical resolution in the usual manner, using a resolving agent, such as , Optically active 1-phenylethylamine, as occasion demands. The compounds of the present invention, obtained by the aforementioned production processes, can be easily isolated and purified by conventional separation means, such as fractional recrystallization, purification using column chromatography, solvent extraction and the like. The phenylethanolaminotetralincarboxamide derivatives, represented by the above general formula (I) of the present invention, can be converted into their pharmaceutically acceptable salts in the usual manner. Examples of such salts include acid addition salts with mineral acids (for example, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, phosphoric acid and the like), the acid addition salts with organic acids (e.g. , formic acid, acetic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, propionic acid, citric acid, succinic acid, tartaric acid, fumaric acid, butyric acid, oxalic acid, malonic acid, maleic acid, lactic acid, malic acid , carbonic acid, glutamic acid, aspartic acid and the like) and salts with inorganic bases, such as a sodium salt and a potassium salt. The resulting salts have the same pharmacological activities, as those of the free forms. In addition, the compounds represented by the above general formula (I) of the present invention also include their hydrates and solvates with pharmaceutically acceptable solvents (e.g., ethanol). The compounds represented by the above general formula (I) of the present invention, exist in two forms of configuration (R) and configuration (S) isomers based on the asymmetric carbon atom having a hydroxy group. Any of the isomers or a mixture thereof, can be employed in the present invention. When the in vitro test was performed to measure the β2-adrenergic receptor stimulating activity in the usual way using pregnant rat pregnant uterus, the compounds represented by the above general formula (I) of the present invention showed an activity to relax the % of spontaneous contractions of rat myometrium (ie, ECso value) at an approximate molar concentration of 5.0 x 10"9 to 5.0 x 10" 6. For example, 2 - [(2S) -2 - [[(2 /?) - 2-hydroxy-2- (4-hydroxyphenyl) -ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy ] -? V, / V-dimethyl acetamide showed the value of Cso at a molar concentration of 1.5 x 10"8. In this way, the compounds of the present invention have a markedly β2-adrenergic receptor stimulating effect. potent, and therefore, are outstandingly useful as β2-adrenergic receptor stimulating agents.When the in vitro test was performed to measure the β-adrenergic receptor stimulating activity in the usual manner using isolated rat atrium, the compounds represented by the above general formula (I) of the present invention showed an activity that increases rat heart rate by 20 beats per minute by the spontaneous mobility of the rat myocardium (ie, EC20 value) at an approximate molar concentration of 1. 0 x 10"6 or more. For example, 2 - [(2S) -2 - [[(2R) -2-hydroxy-2- (4-hydroxyphenyl) -ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] - / V,? / - dimethyl acetamide showed the EC20 value at a molar concentration of 1.6 x 10.6. In this manner, the compounds of the present invention have markedly weaker ßi-adrenergic receptor stimulating effect compared to the aforementioned β2-adrenergic receptor stimulating effect. Accordingly, the compounds of the present invention have markedly potent β2-adrenergic receptor stimulating effect with markedly high selectivity, in comparison with the stimulatory effect of β-adrenergic receptor, so that these are extremely useful and selective β2-adrenergic receptor stimulating agents. with which, the oppressions in the heart are reduced due to the suppression of side effects on the heart (for example, tachycardia) caused by the stimulating effect of ß-adrenergic receptor. The present invention relates to a selective β2-adrenergic receptor stimulating agent, which is extremely useful as, for example, an agent for the prevention of threatened abortion, premature labor, a bronchodilator (an agent for the treatment and prevention of diseases associated with bronchiostenosis or airway obstruction), and an agent for the remission of pain or promote the removal of stones in urolithiasis. In addition, the compounds represented by the above general formula (I) of the present invention are extremely stable compounds and consequently, have excellent storage stability. When the phenylethanolaminotetraincarboxamide derivatives represented by the above general formula (I) of the present invention and the pharmaceutically acceptable salts thereof are used in the practical treatment, they are administered orally or parenterally in the form of appropriate pharmaceutical compositions, such as , tablets, powders, fine granules, granules, capsules, injections and the like. These pharmaceutical compositions can be formulated according to conventional methods, using carriers, excipients and other conventional pharmaceutical additives. The dosage is appropriately determined depending on the sex, age, body weight, degree of symptoms and the like of each patient to be treated, which is approximately in the range from 1 to 1., 000 mg per day per adult human in the case of oral administration, and approximately in the range from 0.01 to 100 mg per day per adult human, in the case of parenteral administration, and the daily dose can be divided into one to several doses per day.

EXAMPLES The contents of the present invention are described in more detail with reference to the following Reference Examples, Examples and Test Examples, but the present invention is not limited thereto. The melting points of the compounds described in the Reference examples and Examples were not corrected.

Reference Example 1 2 - [(2S) -2 - [[(2f? S) -2-hydroxy-2- (4-hydroxyphenyl) -ethyl] amino] -1, 2,3,4-tetrahydronaphthalene-7 iloxy] ethyl acetate. 2-Bromo-4'-hydroxyacetophenone (860 mg) was dissolved in dichloromethane (20 ml), and 3,4-dihydro-2H-pyran (550 μl) and pyridinium p-toluenesulfonate (100 g.) were added. mg) to the solution at room temperature with stirring. After 17 hours of reaction, the reaction mixture was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Purification of the residue by medium pressure liquid column chromatography on silica gel (levigant: hexane / ethyl acetate = 10/1) gave 2-bromo-4 '- ((2f? S) -2-tetrahydropyranyloxy) acetophenone ( 1 .01 g) having a melting point of 1 02-104 ° C.

IR (KBr): 1687 crn "1 1 H NMR (CDC) d ppm: 1.50-2.10 (6H, m), 3.55-3.65 (1 H, m), 3.75-3.90 (1 H, m), 4.41 (2H , s), 5.54 (1 H, t, J = 3.1 Hz), 7.1 1 (2 H, d, J = 9.0 Hz), 7.96 (2 H, d, J = 9.0 Hz) It was dissolved (S) - (2-amino-1, 2,3,4-tetrahydronaphthalen-7-yl-oxy) ethyl acetate (1 .14 g) in / V ,? dimethylformamide (15 ml), and 2-bromo-4 '- ((2RS) -2-tetrahydropyranyloxy) -acetophenone (600 mg) was added to the solution under ice-cooling with stirring, followed by the reaction at room temperature during one hour. Sodium borohydride (380 mg) and ethanol (10 ml) were added to the reaction mixture under cooling with ice under stirring. After one hour of reaction, the reaction mixture was poured into ice water and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate and the solvent was removed in vacuo. The resulting residue was dissolved in tetrahydrofuran (820 ml), triethanolamine (2 ml) was added to the solution and the mixture was heated under reflux for 17 hours. After cooling, water was poured into the reaction mixture and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Purification of the residue by medium pressure liquid column chromatography on silica gel (levigant: ethyl acetate), gave 2 - [(2S) -2 - [[(2RS) -2-hydroxy-2- [4- ((2rs) -2-Tetrahydro-pyranyloxy) phenyl] ethyl] amino] -1, 2,3,4-tetrahydronaphthalen-7-oiloxy-octacetate ethyl (780 mg) as an oil. IR (pure): 3304, 1760 cm "1 1 H NMR (CDC) d ppm: 1.15-1.65 (8H, m), 1.80-2.10 (4H, m), 2.50-3.05 (7H, m), 3.55-3.65 ( 1 H, m), 3.85-3.95 (1 H, m), 4.20-4.30 (2H, m), 4.55-4.70 (3H, m), 5.41 (1 H, t, J = 3.2Hz), 6.61 (1 H, s), 6.69 (1 H, dd, J = 8.4, 2.7Hz), 6.95-7.10 (3H, m), 7.25-7.35 (2H, m) 2 - [(2S) -2 - [[ (2RS) -2-hydroxy-2- [4 - ((2RS) -2-tetrahydro-pyranyloxy) phenyl] ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] ethyl acetate (780 mg) in ethanol (20 ml), and 1N hydrochloric acid (34 ml) was added to the solution under ice-cooling with stirring.After one hour of reaction, the reaction mixture was neutralized with aqueous sodium bicarbonate solution. Saturated and extracted with ethyl acetate.The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo.The purification of the residue by medium pressure liquid column chromatography on silica gel (levigante) : ethyl acetate) gave 2 - [(2S) -2- [[(2f? S) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1, 2,314-tetrahydronaphthalen-7-yloxy] acetate (238 mg) as an amorphous. IR (film): 3294, 1754 cm "1 d ppm: 1 .15-1 .25 (3H, m), 1 .50-1 .65 (1 H, m), 1 .95-2.10 (1 H, m), 2.45-2.60 (1 H, m), 2.65-3.05 (6H, m), 3.73 (3H, br), 4.20-4.30 (2H, m), 4.50-4.70 (3H, m), 6.50-6.60 (1 H, m), 6.67 81 H, dd, J = 8.4, 2.6 Hz), 6.75 (2 H, d, J = 8.4 Hz), 6.97 (1 H, d, J = 8.4 Hz), 7.17 (2 H, d, J = 8.4Hz) Reference Example 2 4 - [(2S) -2 - [[(2f? S) -2- (4-benzyloxyphenyl) -2-hydroxy-ethyl] amino] -1, 2,3,4-tetrahydronaphthalene-7 iloxy] -? /,? / - dimethylbutyramide (S) -2- (fer-butoxycarbonylamino) -7-hydroxytetralin (400 mg) was dissolved in? / ,? dimethylformamide (8 ml), and cesium carbonate (3.16 g) and ethyl 4-bromobutyrate (650 μl) were added to the solution at room temperature with stirring. After 1.5 hours of reaction, water was poured into the reaction mixture and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Purification of the residue by medium pressure liquid column chromatography on silica gel (levigant: hexane / ethyl acetate = 1/1) gave (S) -4- [2- (fer-butoxycarbonyl-amino) -1, 2 Ethyl 3,4-tetrahydronaphthalen-7-yloxy] butyrate (488 mg) having a melting point of 96-98 ° C. IR (KBr): 3360, 1723, 1680 c '1 H NMR (CDCl 3) d ppm: 1.26 (3H, t, J = 7.1 Hz), 1.45 (9H, s), 1.665-1. 80 (1 H, m), 2.00-2.15 (3H, m), 2.50 (2H, t, J = 7.3Hz), 2.59 (1 H, dd, J = 16.5, 7.9Hz), 2.75-2.85 (2H, m), 3.07 (1 H, dd, J = 16.5, 4.6Hz), 3.90-4.05 (3H, m), 4.14 (2H, q, J = 7.1 Hz), 4.50-4.65 (1 H, m), 6.58 (1 H, d, J = 2.6Hz), 6.68 (1 H, dd, J = 8.4, 2.6Hz), 6.99 (1 H, d, J = 8.4Hz) Optical rotation: [a] D25 = -50.7 ° (c = 1 .03, MeOH) (S) -4- [2- (fer-butoxycarbonyllamino) -1,2,3,4-tetrahydro-naphthalen-7-yl-ethylbutyrate (988 mg) was dissolved in a mixed solvent of methanol (15 ml) and ethanol (15 ml), and a 2N aqueous sodium hydroxide solution (3.0 ml) was added to the solution at room temperature with stirring. After 2 hours of reaction, the reaction mixture was concentrated in vacuo. To the resulting residue was added a 10% aqueous citric acid solution and the mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give (S) -4- [2- (re-butoxycarbonylamino) -1,2,3,4-tetrahydro-naphthalen-7-yloxy] butyric acid (914 mg) having a melting point of 150-153 ° C. IR (KBr): 3452, 3365-1691 cm "1 1 H NMR (CDCl 3) d ppm: 1.45 (9H, s), 1.665-1.80 (1 H, m), 2.00-2.20 (3H, m), 2.55-2.70 (3H, m), 2.75-2.85 (2H, m), 3.00-3.15 (1H, m), 3.90-4.10 (3H, m), 4.55-4.70 (1H, m), 6.58 (1 H, d, J = 2.6 Hz), 6.68 (1 H, dd, J = 8.4, 2.6 Hz), 6.99 (1 H, d, J = 8.4 Hz) Optical rotation: [a] D25 = -53.5 ° (c = 0.52, MeOH) (S) -4- [2- (Re-butoxycarbonylamino) -1,2,3,4-tetrahydro-naphthalen-7-yloxy] butyric acid (399 mg) was dissolved in tetrahydrofuran (5 ml), and N was added. , N'-carbonyldi-imidazole (204 mg) to the solution under ice-cooling with stirring. After 2 hours of reaction, a solution of dimethylamine (1.40 g) in tetrahydrofuran (2 ml) was added to the reaction mixture under ice cooling with stirring. After 45 minutes of reaction and then at room temperature for 45 minutes, the reaction mixture was concentrated in vacuo. Water was added to the resulting residue and the mixture was extracted with diethyl ether. The extract was washed with a solution of 10% aqueous citric acid, water, a solution of saturated aqueous sodium bicarbonate and water successively, and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give (S) -4- [2- (fer-butoxycarbonylamino) -1,2,3,4-tetrahydronaphthalen-7-yloxy] -? /, / V-dimethylbutyramide (396 mg) having a melting point of 97-101 ° C. IR (KBr): 3325, 1709, 1624 cm "1 1 H NMR (CDCl 3) d ppm: 1.45 (9H, s), 1.665-1.80 (1 H, m), 2.00-2.15 (3H, m), 2.51 (2H, t, J = 7.2Hz), 2.59 (1 H, dd, J = 16.5, 8.1 Hz), 2.75-2.85 (2H, m), 2.95 (3H, s), 3.00-3.10 ( 4H, m), 3.90-4.00 (3H, m), 4.58 (1 H, br s), 6.59 (1 H, d, J = 2.6 Hz), 6.69 (1 H, dd, J = 8.4, 2.6 Hz) , 6.98 (1 H, d, J = 8.4Hz) Optical rotation: [<X] D25 = -50.0 ° (c = 0.50, MeOH) (S) -4- [2- (Fer-butoxycarbonylamino) -1, 2,3,4, -tetrahydro-naphthalen-7-yloxy] -? /,? / - dimethylbutyramide (396 mg) was dissolved in dichloromethane (5). mi), a solution of trifluoroacetic acid (5 ml) in dichloromethane was added (5 ml) was added to the solution under ice cooling with stirring, and the mixture was still stirred for 15 minutes. After 15 minutes of reaction at room temperature, the reaction mixture was concentrated in vacuo. Dichloromethane, water and sodium bicarbonate were added to the resulting residue and the mixture was stirred at room temperature for 30 minutes. The organic layer was separated and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give (S) -4- (2-amino-1, 2,3,4-tetrahydronaphthalen-7-yloxy) -? /,? / - dimethylburiamide (263 mg) as an oil. IR (pure): 3404, 1618 cm "1 1 H NMR (CDC) d ppm: 1.75-1.90 (1 H, m), 2.00-2.25 (3H, m), 2.45-2.55 (2H, m), 2.65-2.90 (3H, m), 2.94 (3H, s), 3.00 (3H, s), 3.05-3.20 (1H, m), 3.30-3.50 (1H, m), 3.96 (2H, t, J = 5.9Hz ), 5.89 (2H, br s), 6.60 (1 H, d, J = 2.3Hz), 6.68 (1 H, dd, J = 8.4, 2.3Hz), 6.96 (1 H, d, J = 8.4Hz) Optical rotation: [a] D2S = -46.2 ° (c = 0.45, MeOH) (S) -4- (2-amino-1, 2,3,4-tetrahydronaphthalen-7-yloxy) -? /,? / - dimethylbutyramide (196 mg) and triethylamine (270 μl) were dissolved in / V ,? dimethylformamide (3 ml), and a solution of 4'-benzyloxy-2-bromoacetophenone (195 mg) in? /,? / - dimethylformamide (2 ml) was added under ice-cooling with stirring. After 15 minutes of reaction, sodium borohydride (240 mg) and ethanol (3 ml) were added to the reaction mixture under ice-cooling with stirring. After 2 hours of reaction, the reaction mixture was poured into ice water, and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. To the resulting residue was added a solution of triethanolamine (200 mg) in tetrahydrofuran (5 ml), and the mixture was heated under reflux for 16 hours. After cooling, water was poured into the reaction mixture and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Purification of the residue by medium pressure liquid column chromatography on silica gel (levigant: ethyl acetate / ethanol = 6/1) gave 4 - [(2S) -2 - [[(2RS) -2- (4- benzyloxyphenyl) -2- hydroxyethyl] amino] -1, 2,3,4-tetrahydronaphthalen-7-yloxy] -? /,? / - dimethylbutyramide (85 mg) as an amorphous. IR (film): 3348, 1639 cm "1 1 H NMR (CDCl 3) d ppm: 1.55-1.65 (1 H, m), 1.80-2.30 (5H, m), 2.45-2.85 (6H, m), 2.90-3.10 (9H, m), 3.95-4.05 (2H, m), 4.67 (1H, dd, J = 9.1, 3.3Hz), 5.07 (2H, s), 6.60 (1H, s), 6.68 (1H, dd, J = 8.4, 2.7Hz), 6.90-7.05 (3H, m), 7.20-7.50 (7H, m) Reference Example 3 2 - [(2S) -2 - [[(2 /?) -2- (4-benzyloxyphenyl) -2-hydroxyethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] -? /,? / - dimethyl acetamide [R] -4-Hydroxymandelic acid (2.02 g) was dissolved in N, N-dimethylformamide (24 ml), and benzyl bromide (3.57 ml) and potassium carbonate ( 3.65 g) to the solution at room temperature with stirring. After 12 hours of reaction, ice water was poured into the reaction mixture and the resulting precipitates were collected by filtration. The precipitates were suspended in methanol (24 ml) and 1 N aqueous sodium hydroxide solution was added to the suspension under cooling with ice under stirring. After 2 hours of reaction at room temperature, 1N hydrochloric acid (12 ml) was added to the reaction mixture under cooling with ice under stirring. Collection by filtration of the resulting precipitates gave (R) -4-benzyloxymandelic acid (2.43 g) having a melting point of 161-163 ° C. IR (KBr): 3439, 1733 cm "1 1 HN MR (DMSO-d6) d ppm: 4.96 (1H, s), 5.10 (2H, s), 5.75 (1H, br), 6.95-7.05 (2H, m ), 7.25-7.50 (7H, m), 12.52 (1H, br) Optical rotation: [a] D25 = -100.5 ° (c = 1.00, MeOH) (R) -4-Benzyloxymandelic acid (2.43 g), (S) -2-amino-7-hydroxytetralin hydrobromide (2.87 g) and triethylamine (2.88 ml) were dissolved in dichloromethane (38 ml), and hexafluorophosphate was added. benzotriazol-1-yloxytris (dimethylamino) phosphonium (4.58 g) to the solution at room temperature with stirring. After 15 hours of reaction, ethyl acetate was added to the reaction mixture, the resulting mixture was washed with water, 1N hydrochloric acid, a saturated aqueous sodium bicarbonate solution and brine successively, dried over anhydrous magnesium sulfate and the solvent was removed under vacuum . Purification of the residue by medium pressure liquid column chromatography on silica gel (levigant: chloroform / ethyl acetate = 1/1) and following recrystallization from ethyl acetate-hexane, gave (2R) -2- ( 4-benzyloxyphenyl) -2-hydroxy -? - ((2S) -7-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl) acetamide (3.48 g) having a melting point of 137-139 ° C . IR (KBr): 3374, 1630 cm "1 1 H NMR (CDCl 3) d ppm: 1.60-1.75 (1H, m), 1.90-2.00 (1H, m), 2.53 (1H, dd, J = 16.3, 8.3Hz) , 2.60-2.80 (2H, m), 2.97 (1H, dd, J = 16.3, 5.0Hz), 3.43 81H, br), 4.15-4.30 (1H, m), 4.97 (1H, s), 5.03 (2H, s), 5.70 (1H, br), 6.34 (1H, d, J = 8.1Hz), 6.43 (1H, d, J = 2.6Hz), 6.59 (1H, dd, J = 8.3, 2.6Hz), 6.88 ( 1H, d, J = 8.3Hz), 6.93 (2H, d, J = 8.7Hz), 7.20-7.50 (7H, m) Optical rotation: [a] D2S = -89.4 ° (c = 1.06, MeOH) It was dissolved (2 /?) - 2- (4-benzyloxyphenyl) -2-hydroxy- / V - ((2S) -7-hydroxy-1, 2,3,4-tetrahydronaphthalen-2-yl) acetamide (605 mg ) in tetrahydrofuran (7.5 ml), and 2M borane-dimethisulfide complex in tetrahydrofuran (2.25 ml) was added to the solution at room temperature with stirring. After the mixture was heated under reflux for 3 hours, a solution of triethanolamine (1.12 g) in tetrahydrofuran (2.5 ml) was added to the reaction mixture and the mixture was heated under reflux for 15 hours. After cooling, water was poured into the reaction mixture and the resulting mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Recrystallization of the ethyl acetate residue gave (1 R) -1 - (4-benzyloxyphenyl) -2 - [((2S) -7-hydroxy-1, 2,3,4-tetrahydronaphthalen-2-yl) -amino-ethanol (350 mg) having a melting point of 132-134 ° C. IR (KBr): 3250 crn "1 H NMR (CDCl 3) d ppm: 1.20-2.10 (2H, m), 2.50-3.05 (7H, m), 3.50 (1 H, br), 4.60-4.70 (1 H, m), 5.06 (2H, s), 6.50-6.55 (1 H, m), 6.60 (1 H, dd, J = 8.2, 2.7Hz), 6.90-7.00 (3H, m), 7.25-7.50 ( 7H, m) Optical rotation: [a] D2S = -63.1 ° (c = 0.98, MeOH) To a stirred suspension of (1 R) -1 - (4-benzyloxyphenyl) -2 - [((2S) -7-hydroxy-1, 2,3,4-tetrahydronaphthalen-2-yl) amino] -ethanol (350 mg) and N, N-diisopropylethylamine (0.78 ml) in dichloromethane (3.6 ml) were added trifluoroacetic anhydride (0.38 ml) at -15 ° C. After 30 minutes of reaction, the reaction mixture was washed with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. The resulting residue was dissolved in? /,? / - dimethylformamide (4.5 ml), and 2-bromo-? /,? / - dimethylacetamide (0.1 ml), cesium carbonate (880 mg) and sieve powder 4A were added. Molecules (350 mg) to the solution. After the mixture was stirred at room temperature for 2 hours, diethylamine (0.1 ml) was added to the reaction mixture. After 20 minutes of reaction at room temperature, water (3.5 ml) and methanol (3.5 ml) were added to the reaction mixture under cooling with ice and the mixture was stirred at room temperature for 1.5 hours. Brine was emptied into the reaction mixture and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Purification of the residue by medium pressure liquid column chromatography on aminopropyl silica gel (levigant: chloroform / methanol = 50/1) gave 2 - [(2S) -2 - [[(2f?) - 2- (4- benzyloxyphenyl) -2-hydroxy-ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] -? /,? / - dimethylacetamide (283 mg) as an amorphous. IR (KBr): 3430, 1651 cm "1 1 H NMR (CDCl 3) d ppm: 1.35-1.70 (2H, m), 2.00--2.10 (1 H, m), 2.50-3.15 (13H, m ), 3.50 (1 H, br), 4.60-4.70 (3 H, m), 5.07 (2 H, s), 6.65 (1 H, d, J = 2.5 Hz), 6.73 (1 H, dd, J = 8.4, 2.5Hz), 6.90-7.05 (3H, m), 7.25-7.50 (7H, m) Optical rotation: [a] D2S = -61 .0 ° (c = 0.62, MeOH) Reference example 4 The following compounds were prepared according to a reaction and treatment similar to those described in Reference example 3, using 1-bromoacetylpiperidine or 4-bromoacetylmorpholine in place of 2-bromo-β /, / V-dimethylacetamide. 1 - . 1 - [2 - [(2S) -2 - [[(2R) -2- (4-benzyloxyphenyl) -2-hydroxyethyl] -amino-1, 2,3,4-tetrahydronaphthalen-7-yloxy] acetyl] piperidine Amorphous IR (KBr): 3420, 1645 cm "1 1 H NMR (CDCl 3) d ppm: 1.50-1.70 (7H, m), 2.00--2.10 (1 H, m), 2.50-2.65 (1 H, m), 2.70-2.85 (3H, m), 2.95-3.10 (3H, m), 3.45-3.60 (4H, m), 4.63 (2H, s), 4.66 (1H, dd, J = 9.0, 3.5Hz), 5.07 (2H, s), 6.65 (1 H, d, J = 2.7Hz), 6.73 (1H, dd, J = 8.4, 2.7Hz), 6.95-7.05 (3H, m), 7.25-7.50 (7H, m Optical rotation: [a] D2S = -53.0 ° (c = 0.54, MeOH) 4- [2 - [(2s) -2 - [[(2r) -2- (4-benzyloxyphenyl) -2-hydroxyethyl] amino-1, 2,3,4-tetrahydronaphthaIen-7-yloxy] acetyl] morpholine amorphous IR (KBr): 3365, 1653 cm "1 d ppm: 1.55-1.70 (1 H, m), 2.00-2.10 (1 H, m), 2.50-3.10 (7H, m), 3.55-3.75 (9H, m), 4.60-4.70 (3H, m), 5.06 (2H, s), 6.64 (1H, d, J = 2.6Hz), 6.72 (1H, dd, J = 8.4, 2.6Hz), 6.96 ( 2H, d, J = 8.6Hz), 7.00 (1H, d, J = 8.4Hz), 7.25-7.50 (7H, m) Optical rotation: [a] D25 = -49.8 ° (c = 0.59, MeOH) Example Reference 5 2 - [(2S) -2 - [[(2S) -2- (4-benzyloxyphenyl) -2-hydroxyethyl] amino] -1, 2,3,4-tetrahydronaphthalen-7-yloxy] -? ,? dimethyl acetamide 4-benzyloxymandelic acid (40.8 g) was dissolved in methanol (405 ml) and ethyl acetate (405 ml), and a solution of (S) -l-phenylethylamine (20.4 ml) in methanol (200 ml). mi) and ethyl acetate (200 ml) was added to the solution.

After the mixture was allowed to stand at room temperature, the resulting precipitates (37.9 g) were obtained. Recrystallization of the precipitates from methanol (926 ml) gave a salt of (S) -l-phenylethylamine and (S) -4-benzyloxy-mandelic acid (24.8 g) having a melting point of 174-180 ° C. . IR (KBr): 3301, 3036, 1609 crn "1 1H NMR (DMSO-d6) d ppm: 1.42 (3H, d, J = 6.7Hz), 4.27 (1H, q, J = 6.7Hz), 4.50 ( 1 H, s), 5.07 (2H, s), 6.85-6.95 (2H, m), 7.20-8.00 (14H, m) Optical rotation: [a] D25 = + 36.2 ° (c = 0.50, MeOH) A salt of (S) -l-phenylethylamine and (S) -4-benzyloxy-mandelic acid (1.0 g) was suspended and suspended in a mixed solvent of ethyl acetate (20 ml) and water (20 ml), and 1N hydrochloric acid (3.0 ml) was added to the solution under cooling with ice. After the mixture was stirred for 30 minutes, the organic layer was separated, washed with water and dried over anhydrous magnesium sulfate. The solvent was removed in vacuo to give (S) -4-benzyloxymandelic acid (595 mg) having a melting point of 158-162 ° C. IR (KBr): 3440, 1734 cm'1 d ppm: 4.95 (1 H, s), 5.09 (2h, s), 5.70 (1 H, br), 6.90-7.00 (2H, m), 7.25-7.50 ( 7H, m), 12.30 (1 H, br) Optical rotation: [a] D2S = + 99.9 ° (c = 1 .00, MeOH) (S) -4-Benzyloximidelic acid (1.80 g), (S) -2-amino-7-hydroxytetralin hydrobromide (1.87 g) and benzotriazol-1-yloxy-tris (dimethylamino) phosphonium hexafluorophosphate were dissolved. (3.39 g) in N, N-dimethylformamide (21 ml), and triethylamine (2.03 ml) was added to the solution under ice cooling with stirring. After one hour of reaction at room temperature, diethyl ether and water were added to the reaction mixture. Collection by filtration of resulting precipitates gave (2S) -2- (4-benzyloxyphenyl) -2-hydroxy- / V - ((2S) -7-hydroxy-1, 2,3,4-tetrahydronaphthalen-2-yl) acetamide (2.64 g) as powders. IR (KBr): 3487, 3402, 1652 cm "1 1 H NMR (CDCl 3) d ppm: 1.65-1.80 (1 H, m), 1.95-2.10 (1 H, m), 2.53 ( 1 H, dd, J = 16.3, 8.6Hz), 2.65-2.85 (2H, m), 3.00 (1 H, dd, J = 16.3, 5.1 Hz), 4.15-4.20 (1 H, m), 4.99 (1 H, s), 5.06 (2H, s), 6.32 (1 H, d, J = 8.0Hz), 6.48 (1 H, d, J = 2.6Hz), 6.62 (1 H, dd, J = 8.3, 2.6 Hz), 6.85-7.00 (3H, m), 7.20-7.50 (7H, m) Optical rotation: [] D2s = -6.8 ° (c = 1.00, MeOH) Dissolved (2S) -2- (4- benzyloxyphenyl) -2-hydroxy -? / - ((2S) -7-hydroxy-1, 2,3,4-tetrahydronaphthalen-2-yl) acetamide (2.50 g) in tetrahydrofuran (31 ml), and complex of borane-dimethisulfide (1.76 ml) to the solution After the mixture was heated under reflux for 4 hours, a solution of triethanolamine (4.62 g) in tetrahydrofuran (4.6 ml) was added to the reaction mixture and the mixture was added. it was heated under reflux for 11 hours After cooling, water was poured into the reaction mixture and the resulting mixture was extracted with ethyl acetate. it was diluted with water and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Purification of the residue by medium pressure liquid column chromatography on silica gel (levigant: ethyl acetate / ethanol = 7/1) gave (1 S) -1 - (4-benzyloxy-phenyl) -2 - [(( 2S) -7-hydroxy-1, 2,3,4-tetrahydronaphthalen-2-yl) amino] ethanol (1.63 g) as an amorphous. IR (KBr): 3290 cm "1 1 H NMR (CDCl 3) d ppm: 1.55-1.70 (1 H, m), 1.95-2.10 (1 H, m), 2.50-3.05 (7H, m), 3.40 (2H, br), 4.67 (1H, dd, J = 9.1, 3.5Hz), 5.06 (2H, s), 6.50 (1H, d, J = 2.6Hz), 6.60 (1H, dd, J = 8.2, 2.6Hz), 6.93 (1H, d, J = 8.2Hz), 6.96 (2H, d, J = 8.7Hz), 7.20-7.50 (7H, m) Optical rotation: [a] D25 = -1 1 .9 ° (c = 1 .00, CHCI3) To a stirred suspension of (1 S) -1 - (4-benzyloxyphenyl) -2 - [((2S) -7-hydroxy-1, 2,3,4-tetrahydronaphthalen-2-yl) amino] ethanol (1. 30 g) and N, N-diisopropylethylamine (2.91 ml) in dichloromethane (16.7 ml), trifluoroacetic anhydride (1.41 ml) was added at -15 ° C. After 20 minutes of reaction, water was poured into the reaction mixture and the resulting mixture was extracted with dichloromethane. The extract was washed with water and brine, dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. The resulting residue was dissolved in / V,? / - dimethylformamide (8.6 ml) and 2-bromo-? /,? / - dimethylacetamide (571 mg), cesium carbonate (2.52 g) and molecular sieve powder 4A were added ( 860 mg) to the solution. After 2.5 hours of reaction at room temperature, water and methanol were added to the reaction mixture under cooling with ice and the resulting mixture was stirred at room temperature for 12 hours. The insoluble material was filtered and the filtrate was concentrated in vacuo. The resulting residue was dissolved in ethyl acetate, washed with water and brine, and dried over anhydrous magnesium sulfate, and the solvent was removed in vacuo. Recrystallization of the residue from diethyl ether gave 2 - [(2S) -2 - [[(2S) -2- (4-benzyloxyphenyl) -2-hydroxyethyl] amino] 1, 2,3,4-tetrahydronaphthalene -7-yloxy] -? /,? / - dimethylacetamide (437 mg) having a melting point of 103-106 ° C. IR (KBr): 3438, 1672, 1653 cm "1 1 HN MR (CDCl 3) d ppm: 1.50-1.70 (1 H, m), 2.00-2.15 (1 H, m), 2.55-3. 10 (13H, m), 4.60-4.70 (3H, m), 5.07 (2h, s), 6.64 (1H, d, J = 2.8Hz), 6.74 (1H, dd, J = 8.4, 2.8Hz) , 6.97 (2H, d, J = 8.8Hz), 6.99 (1H, d, J = 8.4Hz), 7.20-7.50 (7H, m) Optical rotation: [a] D25 = -14.2 ° (c = 1. 00, CHCI3) Reference Example 6 The following compounds were prepared according to a reaction and treatment similar to those described in Reference Example 5, using 1-bromoacetylpiperidine or 4-bromoacetylmorpholine in place of 2-bromo-β /, / V-dimethylacetamide. Oil of 1- [2 - [(2S) -2 - [[(2S) -2- (4-benzyloxyphenyl) -2-hydroxyethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] acetyl ] piperidine IR (pure): 3304, 1638 cm "1 1 H NMR (CDCl 3) d ppm: 1.50-1.70 (7H, m), 2.00-2.15 (1H, m), 2.50-3.05 (7H, m), 3.40- 3.60 (4H, m), 4.60-4.70 (3H, m), 5.07 (2H, s), 6.64 (1H, d, J = 2.7Hz), 6.73 (1H, dd, J = 8.4, 2.7Hz), 6.90 -7.05 (3H, m), 7.25-7.60 (7H, m) Optical rotation: [a] D25 = -12.1 ° (c = 1.00, CHCI3) 4- [2 - [(2S) -2 - [[(2S) -2- (4-benzyloxyphenyl) -2-hydroxyethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] acetyl] morpholine Amorphous IR (KBr): 3438, 1651 cm "1 d ppm: 1.50-1.70 (1H, m), 2.00-2.10 (1H, m), 2.50-3.10 (7H, m), 3.55-3.75 (9H, m), 4.60-4.70 (3H, m), 5.07 (2H, s), 6.64 (1H, d, J = 2.7Hz), 6.72 (1H, dd, J = 8.4, 2.7Hz), 6.97 ( 2H, d, J = 8.7Hz), 6.98 (1H, d, J = 8.4Hz), 7.25-7.50 (7H, m) Optical rotation: [a] D2S = -26.3 ° (c = 0.50, MeOH) Example 1 2 - [(2S) -2 - [[(2 /? S) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] -amino-1, 2,3,4-tetrahydronaphthalen-7-yloxy] -? /,? / - dimethyl acetamide 2 - [(2S) -2 - [[(2f? S) -2-hydroxy-2- (4-hydroxyphenyl) -ethyl] amino] -1,2, was dissolved Ethyl 3,4-tetrahydronaphthalen-7-yloxy] acetate (250 mg) in tetrahydrofuran (5 ml), and dimethylamine (1 ml) was added to the solution under ice-cooling. After the reaction in a sealed tube at 60 ° C for 60 hours, the reaction mixture was concentrated in vacuo. Purification of the residue by medium pressure liquid column chromatography on aminopropyl silica gel (levigant: ethyl acetate / ethanol = 10/1) gave 2 - [(2S) -2 - [[(2f? S) -2- hydroxy-2- (4-hydroxyphenyl) -ethyl] amino] 1, 2,3,4-tetrahidornaphthalen-7-yloxy] - / ,? -dimethylacetamide (189 mg) as an amorphous. IR (KBr): 3290, 1651 cm "1 1 H-NMR (DMSO-d 6) d ppm: 1.35-1.70 (2H, m), 1.80-2.00 (1 H, m), 2.35-3.05 (13H, m), 4.45-4.55 (1 H, m), 4.65-4.75 (2H, m), 5.06 (1 H, br s), 6.55-6.75 (4H, m), 6.93 (1 H, d, J = 8.4Hz), 7.14 (2H, d, J = 8.3Hz), 9.19 (1H, br s) Example 2 The following compounds were prepared according to a reaction and treatment similar to those described in Example 1 using piperidine, morpholine or pyrrolidine in place of dimethylamine. 1 - . 1 - [2 - [(2S) -2 - [[(2? S) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,4-tetrahydronaphthalen-7-yloxy] acetyl] piperidine amorphous IR (KBr): 3397, 1638 cm "1 1 H-NMR (CDCl 3) d ppm: 1.40-1.70 (7H, m), 2.00--2.10 (1H, m), 2.45-3.10 (7H, m) , 3.40-3.70 (4H, m), 4.60-4.70 (3H, m), 6.62 (1H, d, J = 2.6Hz), 6.65-6.85 (3H, m), 6.97 (1H, d, J = 8.4Hz ), 7.20-7.25 (2H, m) 4- [2 - [(2S) -2 - [[(2RS) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] acetyl] amorphous morpholine IR (KBr): 3402, 1651 cm "1 d ppm: 1.50-1.65 (1H, m), 1.95-2.10 (1H, m), 2.40-2.55 (1H, m), 2.60-3.00 (6H, m ), 3.55-3.75 (8H, m), 4.60-4.70 (3H, m), 6.55-6.65 (1H, m), 6.69 (1H, dd, J = 8.4, 2.7Hz), 6.79 (2H, d, J = 8.5Hz), 6.97 (1H, d, J = 8.4Hz), 7.19 (2H, d, J = 8.5Hz) 1- [2 - [(2S) -2 - [[(2 S) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] acetyl ] amorphous pyrrolidine IR (KBr): 3403, 1643 cm "1 d ppm: 1.45-1.65 (1H, m), 1.70-2.05 (6H, m), 2.10-3.00 (9H, m), 3.45-3.55 (4H, m), 4.55-4.70 (3H, m), 6.58 (1H, dd, J = 8.2, 2.7Hz), 6.65-6.75 (1H, m), 6.80 (2H, d, J = 8.4Hz), 6.96 (1H , d, J = 8.2Hz), 7.18 (2H, d, J = 8.4Hz) Example 3 2 - [(2S) -2 - ([(2R) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] -? / V-dimethylacetamide 2 - [(2S) -2 - [[(2R) -2- (4-benzyloxyphenyl) -2-hydroxyethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] was suspended] -? /,? / - dimethylacetamide (173 mg) and 10% palladium on activated carbon (60 mg) in ethanol (5.5 ml).

After the mixture was stirred at room temperature for 12 hours under hydrogen atmosphere, the catalyst was filtered and the filtrate was concentrated in vacuo. Recrystallization of the resulting residue from methanol gave 2 - [(2S) -2 - [[(2f?) - 2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] 1, 2,3,4-tetrahydro -naphthalene-7-yloxy]?,? / - dimethylacetamide (200 mg), having a melting point of 169-172 ° C. IR (KBr): 3255, 1656 cm "1 1 H-NMR (DMSO-d 6) d ppm: 1.70-1.85 (1H, m), 2.20-2.30 (1H, m), 2.60-2.90 (6H, m), 2.98 (3H, s), 3.00-3.25 (3H, m), 3.35-3.50 (1H, m), 4.73 (2H, s), 4.80-4.95 (1H, m), 6. 02 (1H, br s), 6.65 (1H, d, J = 2.6Hz), 6.70 (1H, dd, J = 8.4, 2.6Hz), 6.78 (2H, d, J = 8.5Hz), 6.99 (1H, d, J = 8.4Hz), 7.22 (2H, d, J = 8.5Hz), 8.80 (1H, br), 9.47 (1H, br s) Rotation optics (hydrochloride): [a] 25 = -69.3 ° (c = 1.01, H2O) Example 4 The following compounds were prepared according to a reaction and treatment similar to those described in Example 3, using the corresponding amide compound in place of 2 - [(2S) -2 - [[(2R) -2- ( 4- benzyloxyphenyl) -2-hydroxyethyl] amino] 1,2,3,4-tetrahydronaphthalen-7-yloxy] -? /,? - dimethylacetamide. 1- [2 - [(2S) -2 - [[(2) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] acetyl] IR amorphous piperidine (KBr): 3309, 1638 cm "1 1 H-NMR (DMSO-de) d ppm: 1.35-1.65 (6H, m), 1.70-1.90 (1H, m), 2.20-2.35 (1H, m) , 2.60-2.90 (3H, m), 3.00-3.50 (8H, m), 4.71 (2H, s), 4.85-5.00 (1H, m), 6.02 (1H, br s), 6.66 (1H, s), 6.71 (1H, dd, J = 8.4, 2.2Hz), 6.78 (2H, d, J = 8.4Hz), 6.99 (1H, d, J = 8.4Hz), 7.22 (2H, d, J = 8.4Hz), 8.90 (1H, br), 9.50 (1H, s) Optical rotation: [a] D25 = -85.2 ° (c = 0.58, MeOH) 4- [2 - [(2S) -2 - [[(2R) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] acetyl] morpholine melting point: 98-101 ° C (recrystallization solvent: chloroform-diethyl ether) IR (KBr): 3393, 1643 cm "1 1 H-NMR (DMSO-d6) d ppm: 1.65-1.80 (1H, m) , 2.10-2.25 (1H, m), 2.60-3.20 (6H, m), 3.25-3.65 (10H, m), 4.70-4.90 (3H, m), 5.88 (1H, br), 6.66 (1H, d, J = 2.5Hz), 6.71 (1H, dd, J = 8.5, 2.5Hz), 6.77 ( 2H, d, J = 8.5Hz), 6.99 (1H, d, J = 8.5Hz), 7.21 (2H, d, J = 8.5Hz), 9.45 (1H, br s) Optical rotation: [a] D25 = - 68.4 ° (c = 0.98, MeOH) 2- [2 - [(2S) -2 - [[(2S) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1, 2,3,4 -tetrahydronaphthalen-7-yloxy]?, / V-dimethylacetamide melting point: 181-183 ° C (recrystallization solvent: ethanol-ethyl acetate) IR (KBr): 3156, 1652 cm "1 1 H-NMR (DMSO- d6) d ppm: 1.35-1.55 (1H, m), 1.85-2.00 (1H, m), 2.30-3.05 (14H, m), 4.45-4.55 (1H, m), 4.69 (2H, s), 5.10 ( 1H, br s), 6.59 (1H, d, J = 2.6Hz), 6.63 (1H, dd, J = 8.4, 2.6Hz), 6.69 (2H, d, J = 8.5Hz), 6.93 (1H, d, J = 8.4Hz), 7.14 (2H, d, J = 8.5Hz), 9.22 (1H, s) Optical rotation: [a] D2S = -24.1 ° (c = 1.00, AcOH) 1- [2 - [(2S) -2 - [[(2S) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] acetyl] IR amorphous piperidine (KBr): 3374, 1634 cm "1 1 H-NMR (DMSO-d6) d ppm: 1.45-1.70 (7H, m), 1.95-2.00 (1H, m), 2.40-2.55 (1H, m) , 2.65-3.00 (8H, m), 3.45-3.60 (4H, m), 4.60-4.70 (3H, m), 6.58 (1H, d, J = 2.7Hz), 6.69 (1H, dd, J = 8.4, 2.7Hz), 6.78 (2H, d, J = 8.5Hz), 6.96 (1H, d, J = 8.4Hz), 7.15 (2H, d, J = 8.5Hz) Optical rotation: [a] D25 = -14.2 ° (c = 1.00, CHCI3) 4- [2 - [(2S) -2 - [[(2S) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] acetyl] amorphous morpholine IR (KBr): 3402, 1649 cm'1 1 H-NMR (DMSO-d6) d ppm: 1.40-1.75 (2H, m), 1.85-2.00 (1 H, m), 2.30-2.95 (7H, m), 3.40-3.65 (8H, m), 4.45-4.55 (1 H, m), 4.72 (2H, s), 5.10 (1 H, d, J = 4.1 Hz), 6.61 (1 H, d, J = 2.6Hz), 6.65 (1H, dd, J = 8.3, 2.6Hz), 6.69 (2H, d, J = 8.5Hz), 6.94 (1H, d, J = 8.3Hz), 7.13 ( 2H, d, J = 8.5Hz), 9.22 (1 H, s) Optical rotation: [a] D25 = -15.5 ° (c = 0.49, MeOH) 4 - [(2S) -2 - [[(2RS) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] - / V? / amorphous -dimethylbutyramide IR (film): 3220, 1616 cm "1 1 H-NMR (DMSO-de) d ppm: 1.35-1.75 (2H, m), 1.80-2.00 (3H, m), 2.35-3.00 (14H, m), 3.31 (1 H, s), 3.85-3.95 (2H, m), 4.45-4.55 (1 H, m), 5.10 (1 H, br s), 6.55-6.75 (4H , m), 6.93 (1 H, d, J = 7.4 Hz), 7.13 (2 H, d, J = 8.4 Hz), 9.22 (1 H, s) Example 5 2 - [(2S) -2 - [[(2 /?) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] 1, 2,3,4-tetrahydronaphthalen-7-yloxy hydrochloride] -? ,? / - dimethylacetamide 2 - [(2S) -2 - [[(2f?) - 2-hydroxy-2- (4-hydroxy-phenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalene was suspended -7-yloxy] -? ,? dimethylacetamide (210 mg) in ethanol (10.5 ml), and 1 N hydrochloric acid (546 ml) was added to the suspension and the mixture was dissolved by heating. After cooling, collection by filtration of the precipitated crystals gave 2 - [(2S) -2 - [[(2-ft-2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2-hydrochloride. 3,4-tetrahydronaphthalen-7-yloxy] -?,? V-dimethylacetamide (100 mg), having a melting point of 165-168 ° C. IR (KBr): 2433, 1652 cm "1 1 H-NMR (DMSO-d 6) d ppm: 1.70-1.90 (1H, m), 2.15-2.30 (1H, m), 2.60-3.60 (13H, m), 4.74 (2H, s), 4.80-4.95 (1H, m), 6.06 (1H, d, J = 2.8Hz), 6.66 (1H, d, J = 2.6Hz), 6.72 (1H, dd, J = 8.4, 2.6Hz), 6.79 (2H, d, J = 8.6Hz), 7.01 (1H, d, J = 8.4Hz), 7.24 (2H, d, J = 8.6Hz), 8.65-9.00 (2H, m), 9.48 (1H, s) Optical rotation: [a] D25 = -69.3 ° (c = 1.01, H2O) Example 6 According to a manner similar to that described in Example 5, the following compounds were prepared from 2 - [(2S) -2 - [[(2R) -2-hydroxy-2- (4-hydroxy in il) ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] -?, / V-dimethylacetamide, using L-tartaric acid or 1 N aqueous sulfuric acid solution. 0. 5 L - Tartrate of 2 - [(2S) -2 - [[(2 /?) - 2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalene-7 iloxy] - / V,? / - dimethylacetamide Melting point: 178-181 ° C (recrystallization solvent: ethanol) IR (KBr): 3634, 3360, 2440, 1659, 1616 cm "1 H-NMR (DMSO-de ) d ppm: 1.50-1.70 (1H, m), 1.95-2.1581H, m), 2.40-3.20 (14H, m), 3.40 (2H, br), 3.79 (1H, s), 4.60-4.80 (3H, m), 5.60 (1H, br), 6.63 (1H, d, J = 2.6Hz), 6.67 (1H, dd, J = 8.3, 2.6Hz), 6.73 (2H, d, J = 8.5Hz), 6.96 (1 H, d, J = 8.3 Hz), 7.18 (2 H, d, J = 8.5 Hz), 9.30 (1 H, br) Optical Rotation: [a] D25 = -64.7 ° (c = 1.03, H2O) Hemisulfate of 2 - [(2S) -2 - [[(2f?) - 2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalen-7-yloxy] -? /,? / - dimethylacetamide Melting point: 202-205 ° C (decomposition) (recrystallization solvent: ethanol) IR (KBr): 2429, 1638 cm "1 1 H-NMR (DMSO-d6) d ppm: 1 .50 -1 .70 (1 H, m), 1.95-2.15 (1 H, m), 2.30-3.30 (15H, m), 4.60-4.80 (3H, m), 5.60 (1H, br), 6.63 (1H, d, J = 2.6Hz), 6.67 (1H, dd, J = 8.4, 2.6Hz), 6. 74 (2H, d, J = 8.5Hz), 6.96 (1H, d, J = 8.4Hz), 7.18 (2H, d, J = 8.5Hz), 9.34 (1 H, br s) Optical rotation: [a] D2S = -65.2 ° (c = 0.50, DMSO) Example 7 According to a manner similar to that described in Example 5, the following compounds were prepared from 1 - [2 - [(2S) -2 - [[(2) -2-hydroxy-2- (4 -hydroxyphenyl) ethyl] amino] -1, 2,3,4-tetrahydronaphthalen-7-yloxy] acetyl] piperidine, using L-tartaric acid or D-tartaric acid. 0. 5 L-tartrate of 1 - [2 - [(2S) -2 - [[(2) -2-hydroxy-2- (4-h id roxif en il) ethyl] a mino] - 1, 2, 3, 4-tetrahydronaphthalen-7-yloxy] acetyl] piperidine Melting point: 208-210 ° C (recrystallization solvent: ethanol) IR (KBr): 3373, 1645 cm "1 1 H-NMR (DMSO-de) d ppm: 1.30 -1 .70 (7H, m), 2.00-2.15 (1 H, m), 2.50-3.25 (7H, m), 3.30-3.50 (4H, m), 3.85 (1 H, s), 4.60-4.75 ( 3H, m), 6.64 (1H, d, J = 2.6Hz), 6.67 (1H, dd, J = 8.4, 2.6Hz), 6.73 (2H, d, J = 8.5Hz), 6.96 (1H, d, J = 8.4Hz), 7.19 (2H, d, J = 8.5Hz), 9.20 (1H, br) Optical rotation: [a] D2S = -66.9 ° (c = 0.55, MeOH) 0. 5 D-tartrate of 1 - [2 - [(2S) -2 - [[(2R) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1, 2,3,4-tetrahydronaphthalene-7 -yloxy] acetyl] pi? eridine Melting point: 206-208 ° C (recrystallization solvent: ethanol) IR (KBr): 3395, 1645 cm "1 1 H-NMR (DMSO-d6) d ppm: 1.35-1.70 (7H, m), 2.00-2.15 (1 H, m), 2.50-3.20 (7H, m), 3.30-3.50 (4H, m), 3.82 (1 H, s), 4.60-4.75 (3H, m), 5.70 (1 H, br), 6.63 (1 H, d, J = 2.7Hz), 6.67 (1H, dd, J = 8.4, 2.7Hz9, 6.73 (2H, d, J = 8.5Hz) 6.96 (1H, d, J = 8.4Hz), 7.18 (2H, d, J = 8.5Hz), 9.30 (1H, br) Optical rotation: [a] D25 = -82.8 ° (c = 0.50, MeOH) Example 8 According to a manner similar to that described in Example 5, the following compounds were prepared from 4- [2 - [(2S) -2 - [[(2) -2-hydroxy-2- (4 -hydroxyphenyl) ethyl] amino] -1,3, 4, 4-tetrahydronaphthalen-7-yloxy] acetyl] morpholine, using L-tartaric acid, D-tartaric acid or fumaric acid. 0. 5 L-Tartrate of 4- [2 - [(2S) -2 - [[(2fi) -2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalene-7 -yloxy] acetyl] morpholine Melting point: 199-201 ° C (recrystallization solvent: ethanol) IR (KBr): 3430, 1652 cm "1 H-NMR (DMSO-d6) d ppm: 1.50-1.70 (1H, m), 2.00-2.15 (1H, m), 2.50-3.20 (7H, m), 3.30-3.70 (8H, m), 3.82 (1H, s9, 4.66 (1H, d, J = 6.2Hz), 4.74 ( 2H, s), 5.70 (1H, br), 6.65 (1H, d, J = 2.5Hz), 6.68 (1H, dd, J = 8.4, 2.5Hz), 6.73 (2H, d, J = 8.5Hz), 6.97 (1H, d, J = 8.4Hz), 7.18 (2H, d, J = 8.5Hz), 9.30 (1H, br) Optical rotation: [a] D2S = -62.6 ° (c = 0.54, MeOH) 0. 5 D-Tartrate of 4- [2 - [(2S) -2 - [[(2f?) - 2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalene- 7-Iloxy] acetyl] morpholine Melting point: 202-204 ° C (recrystallization solvent: ethanol) IR (KBr): 3423, 1655 cm'1 1 H-NMR (DMSO-d6) d ppm: 1.50-1.70 (1H , m), 2.00-2.20 (1H, m), 2.55-3.25 (7H, m), 3.35-3.65 (8H, m), 3.85 (1H, s), 4.68 (1H, dd, J = 9.3, 3.0Hz), 4.74 (2H, s), 5.90 (1H, br), 6.65 (1H, d, J = 2.6 Hz), 6.68 (1H, dd, J = 8.4, 2.6Hz), 6.73 (2H, d, J = 8.5Hz), 6.97 (1H, d, J = 8.4Hz), 7.18 (2H, d, J = 8.5Hz), 9.20 (1H, br) Optical rotation: [a] D S = -71.5 ° (c = 0.54, MeOH) Hemifumarate of 4- [2 - [(2S) -2 - [[(2f?) - 2-hydroxy-2- (4-hydroxyphenyl) ethyl] amino] -1,2,3,4-tetrahydronaphthalene-7 iloxy] acetyl] morpholine Melting point: 193-197 ° C (recrystallization solvent: ethanol) IR (KBr): 3459, 1643 cm "1 1 H-NMR (DMSO-d6) d ppm: 1.50-1.65 (1 H, m), 2.00-2.15 (1 H, m), 2.55-3.20 (7H, m), 3.35-3.70 (8H, m), 4.67 (1 H, dd, J = 9.3, 3.2Hz), 4.74 (2h, s), 6.46 (1 H, s), 6.64 (1 H, d, J = 2.6 Hz), 6.68 (1 H, dd, J = 8.3, 2.6 Hz), 6.73 (2 H, d, J = 8.5 Hz) , 6.96 (1 H, d, J = 8.3 Hz), 7.17 (2 H, d, J = 8.5 Hz), 9.30 (1 H, br) Optical Rotation: [a] D25 = -67.0 ° (c = 0.54, MeOH ) Test Example 1 Drug action in spontaneous contractions of pregnant rat myometrium isolated The uteri of pregnant SD rats (day of pregnancy 21) were isolated and longitudinal strips of uterine muscle were prepared (approximately 15 mm in length and approximately 5 mm wide) free from the basal plate. The experiment was conducted according to the Magnus method. Preparations with a tension of 1 g were exposed to Locke-Ringer solution maintained at 37 ° C and gassed with a mixture of 95% oxygen and 5% carbon dioxide. Spontaneous contractions of myometrium were induced in an isometric manner via a pressure transducer and recorded in a rectigram. The efficacy of the drug was evaluated as 50% inhibitory drug concentration (ie, EC50 value) by comparing the total degree of uterine contraction for 5 minutes before the addition of the drug to the total degree of uterine contraction for 5 minutes after of the medication addition.

Test Example 2 Action of medicaments in the contraction of the isolated rat atrium The atria of SD male rats were isolated (350 to 400 g in body weight) and the experiment was conducted according to the Magnus method. Preparations with a tension of 1 g were exposed to Krebs-Henseleit solution maintained at 37 ° C and gasified with a mixture of 95% oxygen and 5% carbon dioxide. The contraction of the atrium was induced in an isometric manner via a pressure transducer and recorded in a rectigram. After the addition of the drug, its effectiveness was evaluated as a drug concentration, which increases 20 beats per minute of heart rate (ie, EC2o value) - Test Example 3 Acute toxicity A 4-week-old female ICR mice was administered intravenously 2 - [(2S) -2 - [[(2?) - 2-hydroxy-2- (4-hydroxyphenyl) -ethyl ] amino] -1, 2,3,4-tetrahydronaphthalen-7-yloxy] -? /,? / - dimethylacetamide dissolved in saline at a dose of 50 mg / kg. The death of animals was not observed for 24 hours after administration.

Claims (10)

1. A phenylethanolaminotetraincarboxamide derivative represented by the general formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which may contain an oxygen atom in the ring; carbon labeled with * represents a carbon atom in configuration (R), configuration (S) or a mixture thereof, and the carbon atom marked with (S) represents a carbon atom in configuration (S) and a pharmaceutically salt acceptable thereof

2. A phenylethanolaminotetralincarboxamide derivative as claimed in claim 1, represented by the general formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which may contain an oxygen atom in the ring; carbon labeled with (R) represents a carbon atom in (R) configuration, and the carbon atom marked with (S) represents a carbon atom in (S) -configuration and a pharmaceutically acceptable salt thereof.

3. A phenylethanolaminotetralincarboxamide derivative as claimed in claim 2, represented by the formula: (wherein the carbon atom marked with (R) represents a carbon atom in the (R) configuration, and the carbon atom marked with (S) represents a carbon atom in (S) -configuration and a pharmaceutically acceptable salt of the same.

4. A pharmaceutical composition comprising a phenylethanolaminotetraincarboxamide derivative represented by the general formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amine group or a 3 to 7 membered alicyclic amino group, which may contain an oxygen atom in the ring; carbon labeled with * represents a carbon atom in configuration (R), configuration (S) or a mixture thereof, and the carbon atom marked with (S) represents a carbon atom in (S) configuration or a salt pharmaceutically acceptable thereof.

5. A pharmaceutical composition as claimed in claim 4 comprising a phenylethanolaminotetraincarboxamide derivative represented by the general formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which may contain an oxygen atom in the ring; carbon labeled with (R) represents a carbon atom in (R) configuration, and the carbon atom marked with (S) represents a carbon atom in (S) -configuration or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition as claimed in claim 5 comprising a phenylethanolaminotetralincarboxamide derivative represented by the formula: (wherein the carbon atom marked with (R) represents a carbon atom in the (R) configuration, and the carbon atom marked with (S) represents a carbon atom in (S) -configuration or a pharmaceutically acceptable salt of the same.

7. An agent for the prevention of threatened abortion and premature labor, a bronchodilator and an agent for remission of pain and promote the removal of stones in urolithiasis, which comprises, as the active ingredient, a derivative of phenylethanolaminotetralincarboxamide, represented by the General Formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which may contain an oxygen atom in the ring; carbon labeled with * represents a carbon atom in configuration (R), configuration (S) or a mixture thereof, and the carbon atom marked with (S) represents a carbon atom in (S) configuration or a salt pharmaceutically acceptable thereof.

8. An agent for the prevention of threatened abortion and premature labor, a broncho dilator and an agent for remission of pain and promote the removal of stones in urolithiasis as claimed in claim 7, which comprises, as the active ingredient, a phenylethanolaminotetraincarboxamide derivative represented by the general formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which may contain an oxygen atom in the ring, the carbon labeled with (R) represents a carbon atom in (R) configuration, and the carbon atom marked with (S) represents a carbon atom in (S) -configuration or a pharmaceutically acceptable salt thereof.

9. An agent for the prevention of threatened abortion and premature labor, a bronchodilator and an agent for remission of pain and promote the removal of stones in urolithiasis as claimed in claim 8, which comprises, as the active ingredient, a Phenylethanolaminotetralincarboxamide derivative represented by the general formula: (wherein the carbon atom marked with (R) represents a carbon atom in the (R) configuration, and the carbon atom marked with (S) represents a carbon atom in (S) -configuration or a pharmaceutically acceptable salt of the same.

10. A method for the prevention of threatened abortion and premature labor, the prevention and treatment of diseases associated with bronchiostenosis and airway obstruction, and remission of pain and promotion of stone removal in urolithiasis, which comprises, as the ingredient active, a phenylethanolaminotetraincarboxamide derivative represented by the general formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which may contain an oxygen atom in the ring; carbon labeled with * represents a carbon atom in configuration (R), configuration (S) or a mixture thereof, and the carbon atom marked with (S) represents a carbon atom in (S) configuration or a salt pharmaceutically acceptable thereof. eleven . A use of a phenylethanolaminotetraincarboxamide derivative represented by the general formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which may contain an oxygen atom in the ring; of carbon marked with * represents a carbon atom in configuration (/?), configuration (S) or a mixture thereof, and the carbon atom marked with (S) represents a carbon atom in (S) configuration) or a pharmaceutically acceptable salt thereof, for the manufacture of a pharmaceutical composition for the prevention of threatened abortion and premature labor, the prevention and treatment of diseases associated with bronchiostenosis and airway obstruction, and remission of pain and promotion of the removal of stones in urolithiasis. 12. A use of a phenylethanolaminotetralincarboxamide derivative represented by the general formula: (wherein A represents a lower alkylene group, B represents an amino group, a di (lower alkyl) amino group or an alicyclic amino group of 3 to 7 members, which may contain an oxygen atom in the ring, the carbon labeled with * represents a carbon atom in configuration (R), configuration (S) or a mixture thereof, and the carbon atom marked with (S) represents a carbon atom in (S) configuration or a salt pharmaceutically acceptable thereof, as an agent for the prevention of threatened abortion and premature labor, a bronchodilator and an agent for pain remission and promotion of stone removal in urolithiasis.