WO1998013333A1 - Derives de 2-amino-1-(4-hydroxy-2-methylphenyl)propanol - Google Patents

Derives de 2-amino-1-(4-hydroxy-2-methylphenyl)propanol Download PDF

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Publication number
WO1998013333A1
WO1998013333A1 PCT/JP1997/003399 JP9703399W WO9813333A1 WO 1998013333 A1 WO1998013333 A1 WO 1998013333A1 JP 9703399 W JP9703399 W JP 9703399W WO 9813333 A1 WO9813333 A1 WO 9813333A1
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WIPO (PCT)
Prior art keywords
group
carbon atom
amino
general formula
hydroxy
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PCT/JP1997/003399
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English (en)
Japanese (ja)
Inventor
Makio Kitazawa
Kosuke Okazaki
Tetsuro Tamai
Masaru Saito
Nobuyuki Tanaka
Hiroaki Kobayashi
Ken Kikuchi
Hideyuki Muranaka
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Kissei Pharmaceutical Co., Ltd.
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Priority to AU43202/97A priority Critical patent/AU4320297A/en
Publication of WO1998013333A1 publication Critical patent/WO1998013333A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
    • C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
    • C07C217/60—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/18—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides
    • C07C235/20—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having at least one of the singly-bound oxygen atoms further bound to a carbon atom of a six-membered aromatic ring, e.g. phenoxyacetamides having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/07—Optical isomers

Definitions

  • the present invention relates to novel 2-amino-1- (4-hydroxy-12-methylphenyl) propanol derivatives which are useful as pharmaceuticals, and pharmacologically acceptable salts thereof.
  • the present invention relates to a compound represented by the general formula: which has a potent and selective 32 2 -adrenergic receptor stimulating action, and is useful as a ⁇ ⁇ -adrenergic receptor stimulant.
  • one of Y and Z is a general formula — A— C 0 — R
  • a in the formula is a general formula-0-D-E-(D is a lower alkylene group, and E is R is a hydroxyl group, a lower alkyl group, a lower alkoxy group, an alkoxy group, an amino group, a di-lower alkylamino group or a group of 3 to 7 which is a single bond or a phenylene group) or an ethylene group.
  • the other is a hydrogen atom
  • the carbon atom with (R) is a carbon atom in the R configuration
  • (S) is attached.
  • the carbon atom represents the carbon atom in the S configuration.
  • the present invention relates to a 2-amino-1- (4-hydroxy-2-methylphenyl) propanol derivative represented by the formula: and pharmaceutically acceptable salts thereof.
  • Sympathetic - adrenergic receptors the presence of three subtypes of beta iota and 3 3 are known. These subtypes are specifically distributed in each organ, and it is strongly known that there is a species difference in their distribution.
  • Adrenergic receptors are known to be distributed mainly in the heart, adrenergic receptors in the bronchi, uterus, vascular smooth muscle and ureters, and adrenergic receptors in the adipocytes and intestinal tract. I have.
  • ⁇ 2-adrenergic receptor stimulants are used clinically as bronchodilators and threatening flow and premature birth-preventing agents.They have side effects such as tachycardia based on the stimulatory action of ⁇ -adrenergic receptor. Due to concerns, the development of a highly selective ⁇ -adrenergic receptor stimulant having a stimulating effect of) S 2 -adrenergic receptor, which is more potent than that of stimulating adrenergic receptor, has been desired. Disclosure of the invention
  • the present inventors have excellent) 3 2 - Adorenarin receptor agonists intensive studies and as a result to find that certain 2-Amino represented by the general formula (I) - 1 i (4-hydro Kishi 2 - Mechirufuweniru) propanol derivative is potent and selective yS 2 - has ad Renarin receptor stimulating effect,) 8 2 - obtained a finding that it is very useful as adrenergic receptor agonists, forms of the invention Led to.
  • the present invention has the general formula
  • one of Y and Z is a group represented by the general formula A—C 0—R (where A is a group represented by the general formula -0-D-E- (where D is a lower alkylene group, and E is R is a hydroxyl group, a lower alkyl group, a lower alkoxy group, an alkoxy group, an amino group, a di-lower alkylamino group, or a 3- to 7-membered group.
  • the other is a hydrogen atom
  • the carbon atom with (R) is a carbon atom in the R configuration
  • (S) is The carbon atom represents the carbon atom in the S configuration.
  • 2-amino-11- (4-hydroxy-2-methylphenyl) propanol derivatives and their pharmacological properties Pertains to salts that are acceptable.
  • the present invention relates to a medicament containing the 2-amino-1_ (4-hydroxy-2-methylphenyl) pro, ethanol derivative or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention relates to an imminent flow / premature birth inhibitor, a bronchodilator comprising the 2-amino-1- (4-hydroxy-2-methylphenyl) propanol derivative or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention relates to a pain relieving agent for urolithiasis or a lithotripsy accelerator.
  • the present invention relates to a method for preventing urgency and premature birth by administering the 2-amino-1- (4-hydroxyl-2-methylphenyl) propanol derivative or a pharmacologically acceptable salt thereof, and airway obstruction.
  • the present invention relates to a method for preventing or treating dysfunction, a disease caused by bronchial stenosis, and a method for relieving pain in urolithiasis or facilitating stone removal.
  • the present invention relates to the manufacture of a preparation for the prevention of imminent flow and premature birth, the prevention or treatment of diseases caused by airway obstructive disorder and bronchial stenosis, and the manufacture of a preparation for relieving pain in urolithiasis or promoting stone removal.
  • the present invention relates to the use of an amino-1- (4-hydroxy-2-methylphenyl) propanol derivative or a pharmacologically acceptable salt thereof.
  • the present invention relates to the imminent flow of the 2-amino-11- (4-hydroxy-2-methylphenyl) propanol derivative or a pharmacologically acceptable salt thereof ⁇ Preterm labor, bronchodilator, pain relief for urolithiasis It is related to its use as an agent or lithotripsy.
  • a lower alkyl group is a straight-chain or branched alkyl having 1 to 6 carbon atoms such as methyl, ethyl, propyl and isopropyl.
  • a lower alkylene group means a linear or branched alkylene group having 1 to 6 carbon atoms such as a methylene group, an ethylene group, a trimethylene group, and a propylene group; a lower alkoxy group includes a methoxy group and an ethoxy group; A linear or branched alkoxy group having 1 to 6 carbon atoms, such as a group, a propoxy group, an isopropoxy group, etc., and the alkoxy group is the lower alkoxy group having an aryl group such as a phenyl group or a naphthyl group.
  • di-lower alkylamino group refers to an amino group substituted with two of the lower alkyl groups which may be substituted, and a 3- to 7-membered alicyclic amino group refers to an oxygen atom such as 1-pyrrolidinyl group, piperidino group, and morpholino group. Refers to an alicyclic amino group which may be contained.
  • the compound of the present invention represented by the general formula (I) can be produced as follows.
  • one of Y 1 and ⁇ 1 is a group represented by the general formula A—CO—R 1 (wherein R 1 is a hydroxyl group, a lower alkyl group, a lower alkoxy group or an alkoxy group, and A is The other is a hydrogen atom, and the carbon atoms to which (R) and (S) are attached have the same meaning as described above.
  • R 2 is a protecting group for a hydroxyl group, and the carbon atoms to which (R) and (S) are attached have the same meaning as described above). It can be manufactured by removal. Further, among the compounds represented by the general formula (I) of the present invention,
  • Y 2 and ⁇ 2 are either forces, one of which is a general formula— ⁇ —C 0 —R 3 (wherein R 3 is an amino group, a di-lower alkylamino group or a 3- to 7-membered alicyclic amino group)
  • A is a group having the same meaning as described above
  • the other is a hydrogen atom
  • the carbon atoms to which (R) and (S) are attached have the same meanings as described above.
  • one of Y 3 and ⁇ 3 is a group represented by the general formula: 1 -CO—R 4 (wherein R 4 is a lower alkoxy group, and A has the same meaning as described above) And the other is a hydrogen atom, and the carbon atoms to which (R) and (S) are attached have the same meaning as described above.
  • one of Y 4 and Z 4 is a group represented by a general formula—0-D—E—CO—R ′ (D, E and R 1 in the formula have the same meanings as described above) And the other is a hydrogen atom).
  • R 1 has the same meaning as described above.
  • the amine compound represented by the general formula ( ⁇ ) used as a starting material in the production method is represented by the general formula:
  • R 5 is a protecting group for an amino group, and the carbon atom to which (S) is attached has the same meaning as described above).
  • a reducing agent such as sodium borohydride.
  • the compounds of the present invention and salts thereof obtained by the above-mentioned production method can be separated by a conventional separation means such as a fractional recrystallization method, a purification method using column chromatography, It can be easily isolated and purified by the above method.
  • the 2-amino-11- (4-hydroxy-2-methylphenyl) propanol derivative of the present invention represented by the above general formula (I) can be converted into a pharmacologically acceptable salt thereof by a conventional method.
  • salts include acid addition salts with mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, nitric acid, and phosphoric acid, formic acid, acetic acid, methanesulfonic acid, benzenesulfonic acid, p- Acid addition salts with organic acids such as 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, and aspartic acid;
  • salts with inorganic bases such as sodium and potassium
  • salts with organic amines such as morpholine, piperidine
  • the compounds of the present invention also include solvates with pharmaceutically acceptable solvents such as water and ethanol.
  • Preferred compounds among the compounds represented by the general formula (I) of the present invention include 2- [4- [2-[[(1S, 2R) -2-hydroxy-2- (4-hydroxy-12 —Methylphenyl) -1-methylethyl] amino] ethyl] phenoxy] isopropyl acetate, 2- [4-1 (2-([((1S, 2R)) — 2-hydroxy-2- (4-hydroxy-12-methylphenyl) 1-1 -Methylethyl] amino] ethyl] phenoxy] benzyl acetate, 2- [4-1- [2-[[(IS, 2R) —2-hydroxy-2- (4-hydroxy-12-methylphenyl) -1-methylethyl] amino Ethyl] funinoxy] acetic acid and their pharmacologically acceptable salts.
  • the compound represented by the above general formula (I) of the present invention can be obtained by in vitro using a rat extirpated pregnant uterus.
  • O xl O_ 8 ⁇ 8. Indicates 0 X 1 0- 7 molar action to relax 50% automatic movements of uterine smooth muscle by (EC 5. Value) was.
  • 2- [4-1- [2-[[(1S, 2R) -2-hydroxy-12- (4-hydroxy-2-methylphenyl) -1-methylethyl] amino] ethyl] phenoxy] isopropyl acetate is 3 .
  • the value was shown.
  • the compounds of the present invention are non- Always strong yS 2 - are those having adrenergic activity, 3 2 - is very useful as Adore Nalin receptor stimulants.
  • the adrenergic receptor stimulating effect of the compound represented by the above general formula (I) of the present invention was measured by an in vitro test using a rat isolated atria as usual.
  • the compound of the present invention is a compound having extremely weak adrenergic receptor stimulating action.
  • the compound of the present invention has) ⁇ 2 -adrenoceptor stimulating action very strong and ⁇ ⁇ ⁇ , —adrenoceptor stimulating action is extremely weak. It is a selective S 2 -adrenergic receptor stimulant that is extremely useful as a drug, reducing the burden on the heart.
  • the compound of the present invention is a selective ⁇ 2 -adrenoceptor stimulant, an agent for preventing imminent flow / premature birth, a bronchodilator (prophylactic or therapeutic agent for diseases caused by airway obstructive disorder, bronchial stenosis disorder) and It is a very useful compound as a medicinal product such as a pain relieving agent for urolithiasis or a lithotripsy accelerator.
  • 2-amino-1- (4-hydroxy-2-methylphenyl) propanol derivative represented by the general formula (I) of the present invention and a pharmacologically acceptable salt thereof are used for actual treatment
  • an appropriate drug is used. It is orally or parenterally administered as a formulation, for example, as tablets, powders, fine granules, granules, capsules, injections and the like.
  • These pharmaceutical preparations can be prepared by commonly used pharmaceutical methods using commonly used pharmaceutical carriers, excipients and the like.
  • the dose is determined as appropriate depending on the gender, age, weight, degree of symptoms, etc. of the target patient.
  • oral administration generally 1 to 100 mg per adult per day
  • parenteral administration generally For adults, it is administered in a dose of 0.01 to 10 Omg per day, in single or divided doses.
  • reaction solution was poured into ice water, extracted with getyl ether, washed with saturated saline, and dried over anhydrous magnesium sulfate. After evaporating the solvent under reduced pressure, the residue was dissolved in methylene chloride (20 ml), and trifluoroacetic acid (20ral) was added with stirring under ice-cooling, followed by reaction for 1 hour. Concentrate the reaction mixture under reduced pressure and add 2N to the residue. An aqueous sodium hydroxide solution (20 ml), water (20 ral) and getyl ether were added, and the mixture was shaken vigorously to separate the aqueous layer.
  • Example 3 After heating in a sealed tube using the corresponding amine in place of the 28% aqueous ammonia solution, the same treatment as in Example 3 was performed to obtain the following compound.
  • the uterus of an SD pregnant rat (day 2 of pregnancy) was excised, and a specimen about 5 mm in width and about 15 mm in length was made in the longitudinal muscle direction, avoiding the placenta attachment, and was prepared according to the Magnus method. Test was carried out. The sample was suspended at 37 ° C in a L0 cke_Ringer solution aerated with a mixture of 95% oxygen and 5% carbon dioxide, and a 1 g load was applied. Uterine motility was derived isometrically via a pressure transducer and recorded on a rectogram.
  • the efficacy was evaluated by comparing the sum of the uterine contraction height for 5 minutes before the addition of the drug and the sum of the uterine contraction height for 5 minutes after the addition of the drug, and the concentration of the drug that inhibited 50% was evaluated as an EC 50 value.
  • Test example 2
  • the atrium of an SD male rat (body weight 350-400 g) was excised and the experiment was performed according to the Magnus method. Specimens were suspended in Krebs-Henseleit solution aerated with 95% oxygen and 5% carbon dioxide at 37 ° C and loaded with 1 g. The systolic force was derived isometrically via a pressure transducer and recorded on a rectogram. In the drug efficacy evaluation, the drug concentration at the time of increasing the heart rate 20 times per minute by adding the drug was evaluated as an EC 20 value. Test example 3

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Dérivés de 2-amino-1-(4-hydroxy-2-méthylphényl)propanol de formule générale (I), et leurs sels pharmaceutiquement acceptables. Dans ladite formule, l'un des deux éléments Y et Z représente -A-CO-R [dans laquelle A est -O-D-E (avec D représentant alkylène, et E représentant une liaison unique ou phénylène) ou éthylène; et R est hydroxy, alkyle, alcoxy, aralcoxy, amino, dialkylamino ou amino alicyclique], tandis que l'autre représente hydrogène; en outre, les atomes de carbone symbolisés par (R) et (S) sont respectivement ceux des configurations R et S. Les composés considérés ont la propriété de stimuler de manière sélective les récepteurs de β2-adrénaline en allégeant la charge résultante pour le coeur (par exemple, pouls rapide), et ils sont utiles comme médicaments, notamment pour prévenir le danger d'avortement ou l'accouchement avant terme et comme bronchodilatateurs.
PCT/JP1997/003399 1996-09-26 1997-09-25 Derives de 2-amino-1-(4-hydroxy-2-methylphenyl)propanol WO1998013333A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU43202/97A AU4320297A (en) 1996-09-26 1997-09-25 2-amino-1-(4-hydroxy-2-methylphenyl)propanol derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP8/291028 1996-09-26
JP29102896 1996-09-26

Publications (1)

Publication Number Publication Date
WO1998013333A1 true WO1998013333A1 (fr) 1998-04-02

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999005090A1 (fr) * 1997-07-25 1999-02-04 Kissei Pharmaceutical Co., Ltd. Derives d'acide aminoethylphenoxyacetique et medicaments qui reduisent la douleur et favorisent la suppression des calculs dans la lithiase urinaire
WO1999052856A1 (fr) * 1998-04-14 1999-10-21 Kissei Pharmaceutical Co., Ltd. Derives de l'acide 2-methylpropionique et compositions medicinale correspondantes
WO2000002846A1 (fr) * 1998-07-08 2000-01-20 Kissei Pharmaceutical Co., Ltd. Derives d'acide phenoxyacetique et compositions medicinales contenant lesdits derives
WO2000043350A1 (fr) * 1999-01-21 2000-07-27 Kissei Pharmaceutical Co., Ltd. Polymorphisme cristallin de derive d'acide aminoethylphenoxyacetique

Citations (5)

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Publication number Priority date Publication date Assignee Title
JPS565444A (en) * 1979-06-16 1981-01-20 Beecham Group Ltd Ethanamine derivative* its manufacture and its medicinal composition
JPS56138150A (en) * 1980-03-28 1981-10-28 Tanabe Seiyaku Co Ltd Novel benzyl alcohol derivative and its preparation
JPS6067450A (ja) * 1983-08-17 1985-04-17 ビ−チヤム・グル−プ・ピ−エルシ− ２−フエニルエチルアミン誘導体．その製法及びそれを含む医薬組成物
JPS6176446A (ja) * 1984-07-19 1986-04-18 ビ−チヤム・グル−プ・ピ−エルシ− 新規化合物、その製法及びそれを含む医薬組成物
JPS62228011A (ja) * 1986-03-03 1987-10-06 ビーチャム・グループ・ピーエルシー 新規な医薬組成物

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Publication number Priority date Publication date Assignee Title
JPS565444A (en) * 1979-06-16 1981-01-20 Beecham Group Ltd Ethanamine derivative* its manufacture and its medicinal composition
JPS56138150A (en) * 1980-03-28 1981-10-28 Tanabe Seiyaku Co Ltd Novel benzyl alcohol derivative and its preparation
JPS6067450A (ja) * 1983-08-17 1985-04-17 ビ−チヤム・グル−プ・ピ−エルシ− ２−フエニルエチルアミン誘導体．その製法及びそれを含む医薬組成物
JPS6176446A (ja) * 1984-07-19 1986-04-18 ビ−チヤム・グル−プ・ピ−エルシ− 新規化合物、その製法及びそれを含む医薬組成物
JPS62228011A (ja) * 1986-03-03 1987-10-06 ビーチャム・グループ・ピーエルシー 新規な医薬組成物

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Title
BR. J. CLIN. PHARMACOL., (1993), 36(6), NEWNHAM D.M., INGRAM C.G., MACKIE A., LIPWORTH B.J., "Beta-Adrenoceptor Subtypes Mediating the Airways Response to BRL 35135 in Man", pages 567-571. *
BR. J. PHARMACOL., (1993), 110(4), MARTIN CORINNE A.E., NALINE EMMANUEL, MANARA LUCIANO, ADVENIER CHARLES, "Effects of two Beta3-Adrenoceptor Agonists, SR 58611A and BRL 37344 and of Salbutamol on Cholinergic and NANC Neural Contraction in Guinea Pig Main Bronchi In Vitro", pages 1311-1316. *
FARM. AIKAK., (1973), 82(7-8), HALMEKOSKI JAAKKO, MAUKONEN LIISA, "Selective Acetylations of Terbutaline and Ritodrine", pages 111-115. *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999005090A1 (fr) * 1997-07-25 1999-02-04 Kissei Pharmaceutical Co., Ltd. Derives d'acide aminoethylphenoxyacetique et medicaments qui reduisent la douleur et favorisent la suppression des calculs dans la lithiase urinaire
WO1999052856A1 (fr) * 1998-04-14 1999-10-21 Kissei Pharmaceutical Co., Ltd. Derives de l'acide 2-methylpropionique et compositions medicinale correspondantes
US6696489B1 (en) 1998-04-14 2004-02-24 Kissei Pharmaceutical Co., Ltd. 2-Methylpropionic acid derivatives and medicinal compositions containing the same
WO2000002846A1 (fr) * 1998-07-08 2000-01-20 Kissei Pharmaceutical Co., Ltd. Derives d'acide phenoxyacetique et compositions medicinales contenant lesdits derives
US6538152B1 (en) 1998-07-08 2003-03-25 Kissei Pharmaceutical Co., Ltd. Phenoxyacetic acid derivatives and medicinal compositions containing the same
AU771200B2 (en) * 1998-07-08 2004-03-18 Kissei Pharmaceutical Co. Ltd. Phenoxyacetic acid derivatives and medicinal compositions containing the same
WO2000043350A1 (fr) * 1999-01-21 2000-07-27 Kissei Pharmaceutical Co., Ltd. Polymorphisme cristallin de derive d'acide aminoethylphenoxyacetique
CZ302572B6 (cs) * 1999-01-21 2011-07-20 Kissei Pharmaceutical Co. Ltd. Krystalická polymorfní forma derivátu kyseliny aminoethylfenoxyoctové

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