WO1995019336A1 - Ethers de phenylethanolamine et leur utilisation comme agonistes des recepteurs adrenergiques beta - Google Patents

Ethers de phenylethanolamine et leur utilisation comme agonistes des recepteurs adrenergiques beta Download PDF

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Publication number
WO1995019336A1
WO1995019336A1 PCT/EP1995/000082 EP9500082W WO9519336A1 WO 1995019336 A1 WO1995019336 A1 WO 1995019336A1 EP 9500082 W EP9500082 W EP 9500082W WO 9519336 A1 WO9519336 A1 WO 9519336A1
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WIPO (PCT)
Prior art keywords
phenyl
compounds
ethanol
alkyl
hexylamino
Prior art date
Application number
PCT/EP1995/000082
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German (de)
English (en)
Inventor
Jan Bron
Geert Jan Sterk
Hendrik Timmerman
Meta E. J. Veerman
Jan Fetze Van Der Werf
Albert D. Windhorst
Original Assignee
Iovis Biomedical And Pharmaceutical Consultants
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Iovis Biomedical And Pharmaceutical Consultants filed Critical Iovis Biomedical And Pharmaceutical Consultants
Priority to AU15334/95A priority Critical patent/AU1533495A/en
Publication of WO1995019336A1 publication Critical patent/WO1995019336A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • 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
    • C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
    • C07C217/08—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom
    • 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
    • C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
    • C07C217/08—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom
    • C07C217/10—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to an acyclic carbon atom to an acyclic carbon atom of a hydrocarbon radical containing six-membered aromatic rings
    • 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
    • C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C217/06—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted
    • C07C217/14—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring
    • C07C217/16—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one etherified hydroxy group and one amino group bound to the carbon skeleton, which is not further substituted the oxygen atom of the etherified hydroxy group being further bound to a carbon atom of a six-membered aromatic ring the six-membered aromatic ring or condensed ring system containing that ring not being further substituted

Definitions

  • the invention relates to new compounds, processes for their preparation and their use as active ingredients in pharmaceuticals.
  • Rl is hydrogen or 1-4C-alkyl
  • R2 is a phenyl radical substituted by R3 and R4, a pyridyl radical, a phenoxy radical, a naphthyl radical, a thienyl radical or one
  • R3 is hydrogen, halogen, hydroxy (-0H), 1-4C-alkyl, 1-4C-alkoxy,
  • R3 and R4 together form a methylenedioxy (-0-CH - 0-) or ethylenedioxy radical (-0-CH - CH - 0-), is an integer from 4 to 10 and n is an integer from 0 to 7, and the salts of these compounds, where m is not the number 4 or 5 when n is the number 0.
  • 1-4C-Alkyl stands for straight-chain or branched alkyl radicals with 1 to 4 carbon atoms. Examples include the butyl, iso-butyl, sec-butyl, tert-butyl, propyl, isopropyl, ethyl and especially the methyl radical.
  • Halogen in the sense of the present invention is bromine, chlorine and fluorine.
  • 1-4C-alkoxy radicals contain one of the 1-4C-alkyl radicals mentioned above.
  • the methoxy radical is preferred.
  • 1-4C-alkoxycarbonyl radicals contain one of the 1-4C-alkoxy radicals mentioned above.
  • the methoxycarbonyl and ethoxycarbonyl radicals may be mentioned as the 1-4C-alkoxycarbonyl ester R3.
  • Di-1-4C-alkylcarbamoyl radicals are substituted on the nitrogen atom by two identical or different of the above-mentioned 1-4C-alkyl radicals.
  • the diethylcarbamoyl radical may be mentioned as dial-4C-alkylcarbamoyl radical R3.
  • Examples of mono- or di-1-4C-alkylamino residues are methylamino, dimethylamino and diethyla inorest.
  • Suitable salts for compounds of the formula I are preferably all acid addition salts.
  • Pharmacologically incompatible salts which may initially be obtained as process products in the preparation of the compounds according to the invention on an industrial scale, are converted into pharmacologically acceptable salts by processes known to the person skilled in the art.
  • Suitable as such are water-soluble and water-insoluble acid addition salts with acids such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-gluconic acid, benzoic acid, 2- (4-hydroxybenzoyl) benzoic acid, butyric acid, sulfosalicylic acid, maleic acid, maleic acid Lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, embonic acid, stearic acid, toluenesulfonic acid, methanesulfonic acid or 3-hydroxy-2-naphthoic acid, the acids in the salt production - depending on whether it is a mono- or respectful acid and, depending on which salt is desired, be used in an equimolar or a different ratio.
  • acids such as, for example, hydrochloric acid, hydrobromic acid, phosphoric acid, ni
  • Rl is hydrogen or 1-4C-alkyl
  • R2 represents a phenyl radical substituted by R3 and R4 or a pyridyl radical, where
  • R3 is hydrogen, halogen, hydroxy (-0H), 1-4C-alkyl, 1-4C-alkoxy, benzyloxy, nitro (-NC) or trifluoromethyl (-CF 3 ) and
  • R4 is hydrogen, hydroxy (-0H), 1-4C-alkyl or 1-4C-alkoxy, or wherein
  • R3 and R4 together form a methylenedioxy (-0-CH - 0-) or ethylenedioxy radical (-0-CH - CH - 0-), m is an integer from 4 to 8 and n is an integer from 1 to 5, and the salts of these compounds.
  • Particularly noteworthy are compounds of the formula I in which
  • Rl is hydrogen
  • R2 represents a phenyl radical substituted by R3 and R4 or a pyridyl radical, where
  • R3 is hydrogen, halogen, hydroxy (-0H), 1-4C-alkyl or 1-4C-alkoxy and
  • R4 is hydrogen or 1-4C-alkyl, is an integer from 4 to 6 and n is an integer from 2 to 4, and the salts of these compounds.
  • the invention further relates to a process for the preparation of the compounds of the formula I and their salts.
  • the method is characterized in that a) compounds of the formula II,
  • Rl, R2, m and n have the meanings given above and Bz represents a benzyl group, reductively debenzylated, or that one
  • R2, m and n have the meanings given above and L represents a suitable leaving group, and that, if desired, the compounds I obtained according to a) or b) are subsequently converted into their salts, or if desired subsequently subsequently obtained salts of the compounds I releases the compounds I.
  • Debenzylation according to process variant a) is carried out in a manner familiar to the person skilled in the art, e.g. with hydrogen in the presence of palladium as a catalyst (in methanol or ethanol at room temperature) or with sodium in liquid ammonia (at -80'C).
  • the reaction of the compounds III with the compounds IV is carried out in a manner known per se to the person skilled in the art in inert, preferably polar solvents, for example in methanol, ethanol, 1- or 2-propanol, dimethyl formate, tetrahydrofuran, acetone, methyl ethyl ketone , Methyl isobutyl ketone or dioxane, at temperatures between 10 and 120 ⁇ C, preferably between 50 and 100 ⁇ C, optionally at the boiling point of the solvent used.
  • the reaction is carried out in the presence of a base, for example a tertiary organic amine, such as diisopropylethylamine, or an inorganic carbonate, such as potassium carbonate.
  • leaving groups L are suitable on the basis of his specialist knowledge.
  • the tosylate or the mesylate group but especially halogen atoms, and especially chlorine or bromine, are suitable.
  • chlorine or bromine compounds IV are used, the reaction can advantageously also take place in the presence of catalytic amounts of an iodide, such as, for example, potassium iodide.
  • the compounds according to the invention are initially obtained either as such or in the form of their salts.
  • the salts are obtained by dissolving the free compounds in a suitable solvent, e.g. in a chlorinated hydrocarbon, such as methylene chloride or chloroform, a low molecular weight aliphatic alcohol (ethanol, isopropanol), an ether (diisopropyl ether), a ketone (acetone) or water, which contains the desired acid, or which contains the desired acid - if necessary in the precisely calculated stoichiometric amount - is then added.
  • a suitable solvent e.g. in a chlorinated hydrocarbon, such as methylene chloride or chloroform, a low molecular weight aliphatic alcohol (ethanol, isopropanol), an ether (diisopropyl ether), a ketone (acetone) or water, which contains the desired acid, or which contains the desired acid - if necessary in the precisely calculated stoichiometric amount - is then added.
  • the salts are obtained by filtration, rep
  • the starting compound II is obtained by reacting the benzylamines V,
  • the reaction of the benzylamines V with the epoxides VI is carried out in a manner known per se (for example analogously to RK Atkins, J. Frazier, LL Moore and LO Wiegel, Tetrahedron Lett. 1986, 27, 2451-2454), for example by several hours Heating under reflux in a suitable inert solvent, such as 2-propanol.
  • the benzylamines V are obtained by reacting the compounds IV with benzylamine in a manner known per se, for example by heating to 100 to 150 ° C. without a further solvent with the addition of a suitable auxiliary base, e.g. a tertiary amine, or using an excess of benzylamine.
  • a suitable auxiliary base e.g. a tertiary amine
  • the compounds of the formula IV are known or they can be prepared by methods known per se (for example analogously to A. McKillop, J.-C. Fiaud and RP Hug, Tetrahedron, 1974, 30, 1379-1382 or analogously to HH Freedman and RA Dubois , Tetrahedron Lett. 1975, 38, 3251-3254).
  • a solution of 7 mmol of the starting compound IV, 10 mmol of the compound III, 1.0 g of potassium iodide and 4 ml of diisopropylethylamine in 50 ml of diethyl amide is heated to 90 ° C. for 2 h with nitrogen gas. After concentration, the residue is taken up in a mixture of aqueous sodium carbonate solution and ethyl acetate. The organic phase is dried over magnesium sulfate and concentrated, the residue is purified by chromatography and / or recrystallization.
  • the chromatography is carried out on silica gel using ethyl acetate / triethylamine (mixture P) or petroleum ether 60-80 / ethyl acetate / triethylamine (mixture Q).
  • the compounds according to the invention have valuable pharmacological properties which make them commercially usable. They are primarily effective ß-adrenoceptor agonists (ß-sympathomimetics) with a ß 2 -stimulating effect, whereby they are characterized by their good solubility.
  • the compounds according to the invention are suitable, for example, for the treatment of bradycardia and conduction disorders and increase the contractility of the heart, they can be used as tocolytics for the treatment of premature labor, they generally act as vasodilants and can be used for treatment (peri- circulatory disorders are used, they lead to a relaxation of the bladder wall muscles and are suitable for the treatment of bladder emptying disorders, they lower the (pathologically increased) intraocular pressure and can be used to treat glaucoma, they influence the metabolism and are suitable, for example for the treatment of obesity, and because of their ß - sympathomimetic effect they are particularly suitable for the treatment of respiratory diseases of various origins.
  • bronchial diseases due to the broncholytic effectiveness of the compounds according to the invention can be treated.
  • the compounds according to the invention are distinguished by a low toxicity, a large therapeutic breadth, a long-lasting effect and reduced systemic side effects. Of particular importance in this context is - compared to systemic application - the pronounced effectiveness with topical application.
  • the broncholytic activity of the compounds according to the invention enables them to be used in human and veterinary medicine, and they are used for the treatment and prophylaxis of diseases which are based on diseases of the bronchi.
  • diseases which are based on diseases of the bronchi.
  • acute and chronically obstructive respiratory diseases of various origins bronchitis, allergic see bronchitis, bronchial asthma
  • bronchitis acute and chronically obstructive respiratory diseases of various origins
  • bronchitis allergic see bronchitis, bronchial asthma
  • the properties of the compounds according to the invention also enable their use in the topical treatment of dermatoses, for example in the case of inflammatory and allergic skin diseases, such as, for example, toxic and allergic contact dermatitis, atopic eczema, seborrheic eczema, follicular and areal pyoderma, endogenous and exogenous acne and acne rosacea.
  • dermatoses for example in the case of inflammatory and allergic skin diseases, such as, for example, toxic and allergic contact dermatitis, atopic eczema, seborrheic eczema, follicular and areal pyoderma, endogenous and exogenous acne and acne rosacea.
  • the compounds according to the invention are suitable for the treatment of those disease states which are known to be positively influenced by the application of certain ⁇ -adrenoceptor agonists.
  • metabolic disorders of various origins e.g. obesity or disorders such as those associated with diabetes
  • Gastrointestinal motility disorders and pathological changes in the gastrointestinal tract for example inflammatory bowel diseases such as ulcerative colitis or Crohn's disease
  • Another object of the invention is therefore a method for the treatment of mammals, including humans, who are suffering from one of the abovementioned diseases.
  • the method is characterized in that the sick mammal is administered a therapeutically effective and pharmacologically acceptable amount of one or more of the compounds according to the invention.
  • the invention furthermore relates to the compounds according to the invention for use in the treatment and / or prophylaxis of the diseases mentioned.
  • the invention also relates to the use of the compounds according to the invention for the production of medicaments which are used for the treatment and / or prophylaxis of the diseases mentioned.
  • the invention furthermore relates to medicaments for the treatment and / or prophylaxis of the diseases mentioned which contain one or more of the compounds according to the invention and / or their pharmacologically tolerable salts.
  • the medicaments according to the invention are produced by methods known per se, reference being made, for example, to the statements in European patent 163 965 with regard to the preparations, the dosage forms (in particular with regard to inhalation administration), etc.
  • inhalative administration is particularly important in the treatment of bronchial diseases, for which the compounds according to the invention appear to be outstandingly suitable on account of their activity profile.
  • daily doses of 0.01 to 2.0 mg, in particular 0.05 to 1.0 mg are advantageously administered in several individual doses to, for example, 10 to 50 ⁇ g of active ingredient.
  • doses from 0.5 to 50 mg per day, if appropriate in the form of several individual doses, are to be administered.
  • the excellent bronchospasmolytic effect of the compounds according to the invention can be demonstrated by in vitro investigations on the guinea pig trachea.
  • the relaxing effect on a guinea pig trachea is measured for the compounds to be examined, which has previously been contracted with a suitable dose of metacholine.
  • the trachea of male guinea pigs (200-300 g) is removed, divided into individual segments and each segment is in an organ bath with 120 mM NaCl, 6 M KCl, 1 mM MgSO 4 , 2.5 mM CaCl 1 M NaH -P0 4 , 2.5 M NaHC0 3 and 6 mM glucose at 35 ⁇ C suspended.
  • Oxygen mixed with 5% CO 2 , is continuously passed through the solution. After stabilization, the trachea is contracted with a suitable dose of methacholine. A dose-response curve is then recorded in a cumulative manner with the test substances. The concentration ( ⁇ mol / 1) is then determined from this curve, which corresponds to 50% of the maximum effect (EC 5Q ). This EC. Q is thus a measure of the activity of the compounds according to the invention.

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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

L'invention concerne des composés de la formule (I): C6H5-CH(OH)-CH(R1)-NH-(CH2)m-O-(CH2)nR2, et leurs sels, dans laquelle R1 désigne hydrogène ou alkyle 1-4C, R2 désigne un reste phényle substitué par R3 et R4, un reste pyridyle, un reste phénoxy, un reste naphtyle, un reste thiényle ou un reste benzhydryle; R3 désignant hydrogène, halogène, hydroxy (-OH), alkyle 1-4C, alcoxy 1-4C, benzyloxy, nitro (-NO2), trifluorométhyle (-CF3), alcoxycarbonyle (-CO-O-alkyle 1-4C), carbamoyle (-CO-NH2), di-alkylcarbamoyle [-CO-N(alkyle 1-4C)2], amino (-NH2) ou mono- ou di-(alkyle 1-4C) amino et R4 désignant hydrogène, halogène, hydroxy (-OH), alkyle 1-4C ou alcoxy 1-4C, ou R3 et R4 constituant conjointement un reste méthylène-dioxy (-O-CH2-O-) ou un reste éthylène-dioxy (-O-CH2-CH2-O-), m vaut un nombre entier compris entre 4 et 10 et n vaut un nombre entier compris entre 0 et 7, m ne pouvant valoir 4 ou 5 lorsque n vaut 0. Ces composés présentent des propriétés pharmacologiques précieuses. Ils constituent en tout premier lieu des agonistes efficaces des récepteurs adrénergiques β (sympathomimétiques β) exerçant notamment une action β2-stimulante et se caractérisent par une bonne solubilité.
PCT/EP1995/000082 1994-01-12 1995-01-11 Ethers de phenylethanolamine et leur utilisation comme agonistes des recepteurs adrenergiques beta WO1995019336A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU15334/95A AU1533495A (en) 1994-01-12 1995-01-11 Phenyl ethanol amine ethers and uses thereof as beta-adreno-receptor agonists

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH8594 1994-01-12
CH85/94-3 1994-01-12

Publications (1)

Publication Number Publication Date
WO1995019336A1 true WO1995019336A1 (fr) 1995-07-20

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Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003074458A1 (fr) * 2002-03-05 2003-09-12 Boehringer Ingelheim Pharma Gmbh & Co Kg Procede ameliore de production de 4-(6-bromohexyloxy)-butylbenzene
WO2003097073A1 (fr) * 2002-04-19 2003-11-27 Astion Development A/S Combinaison d'agonistes de recepteur adrenergique beta-2 et d'un sucre amine et leur utilisation pour le traitement de troubles immunomodulateurs
WO2004016578A2 (fr) * 2002-07-25 2004-02-26 Glaxo Group Limited Composes medicamenteux
WO2004037768A2 (fr) * 2002-10-28 2004-05-06 Glaxo Group Limited Composes a usage medicinal
US6835857B2 (en) 2002-03-05 2004-12-28 Boehringer Ingelheim Pharma Gmbh & Co. Kg Process for the manufacture of 4-(6-bromohexyloxy)-butylbenzene
EP1719507A1 (fr) 2005-04-13 2006-11-08 Astion Development A/S Des agonistes de bêta-2 adrénocepteur pour le traitement de maladies du tissus conjonctifs
US7361787B2 (en) 2001-09-14 2008-04-22 Glaxo Group Limited Phenethanolamine derivatives for treatment of respiratory diseases
US7538127B2 (en) 2003-02-14 2009-05-26 Glaxo Group Limited Medicinal compounds
JP4782961B2 (ja) * 1999-06-11 2011-09-28 富山化学工業株式会社 Ｎ−アルコキシアルキル−ｎ，ｎ−ジアルキルアミン誘導体またはその塩、それらを含有する神経変性疾患の治療剤

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FR2119844A1 (fr) * 1970-12-28 1972-08-11 Laroche Navarron Lab
EP0040000A1 (fr) * 1980-05-08 1981-11-18 Beecham Group Plc Dérivés d'aryléthanolamine, leur préparation et leur utilisation dans des compositions pharmaceutiques
US4460580A (en) * 1978-06-05 1984-07-17 Ciba-Geigy Corporation N-Alkylated aminoalcohols and their pharmaceutical compositions useful for the treatment of cardiac insufficiency
EP0220054A2 (fr) * 1985-10-16 1987-04-29 Glaxo Group Limited Dérivés d'éthanolamine
EP0303464A2 (fr) * 1987-08-11 1989-02-15 Glaxo Group Limited Dérivés de chloroaniline
GB2230525A (en) * 1989-04-14 1990-10-24 Glaxo Group Ltd 1-(Hydroxyphenyl)-2-aminoethanol derivatives

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Publication number Priority date Publication date Assignee Title
FR2119844A1 (fr) * 1970-12-28 1972-08-11 Laroche Navarron Lab
US4460580A (en) * 1978-06-05 1984-07-17 Ciba-Geigy Corporation N-Alkylated aminoalcohols and their pharmaceutical compositions useful for the treatment of cardiac insufficiency
EP0040000A1 (fr) * 1980-05-08 1981-11-18 Beecham Group Plc Dérivés d'aryléthanolamine, leur préparation et leur utilisation dans des compositions pharmaceutiques
EP0220054A2 (fr) * 1985-10-16 1987-04-29 Glaxo Group Limited Dérivés d'éthanolamine
EP0303464A2 (fr) * 1987-08-11 1989-02-15 Glaxo Group Limited Dérivés de chloroaniline
GB2230525A (en) * 1989-04-14 1990-10-24 Glaxo Group Ltd 1-(Hydroxyphenyl)-2-aminoethanol derivatives

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP4782961B2 (ja) * 1999-06-11 2011-09-28 富山化学工業株式会社 Ｎ−アルコキシアルキル−ｎ，ｎ−ジアルキルアミン誘導体またはその塩、それらを含有する神経変性疾患の治療剤
US7982067B2 (en) 2001-09-14 2011-07-19 Glaxo Group Limited Phenethanolamine derivatives for treatment of respiratory diseases
US7439393B2 (en) 2001-09-14 2008-10-21 Glaxo Group Limited Phenethanolamine derivatives for treatment of respiratory diseases
USRE44874E1 (en) 2001-09-14 2014-04-29 Glaxo Group Limited Phenethanolamine derivatives for treatment of respiratory diseases
US7361787B2 (en) 2001-09-14 2008-04-22 Glaxo Group Limited Phenethanolamine derivatives for treatment of respiratory diseases
US8198483B2 (en) 2001-09-14 2012-06-12 Glaxo Group Limited Phenethanolamine derivatives for treatment of respiratory diseases
US7776895B2 (en) 2001-09-14 2010-08-17 Glaxo Group Limited Inhalation devices for delivering phenethanolamine derivatives for the treatment of respiratory diseases
US6835857B2 (en) 2002-03-05 2004-12-28 Boehringer Ingelheim Pharma Gmbh & Co. Kg Process for the manufacture of 4-(6-bromohexyloxy)-butylbenzene
WO2003074458A1 (fr) * 2002-03-05 2003-09-12 Boehringer Ingelheim Pharma Gmbh & Co Kg Procede ameliore de production de 4-(6-bromohexyloxy)-butylbenzene
US7112701B2 (en) 2002-03-05 2006-09-26 Boehringer Ingelheim Pharma Gmbh & Co. Kg Process for the manufacture of 4-(6-bromohexyloxy)-butylbenzene
EA007906B1 (ru) * 2002-04-19 2007-02-27 Астион Девелопмент А/С Комбинация агониста бета-2-адренорецепторов и аминосахара и их применение для лечения иммуномодуляторных расстройств
WO2003097073A1 (fr) * 2002-04-19 2003-11-27 Astion Development A/S Combinaison d'agonistes de recepteur adrenergique beta-2 et d'un sucre amine et leur utilisation pour le traitement de troubles immunomodulateurs
WO2004016578A3 (fr) * 2002-07-25 2004-06-10 Glaxo Group Ltd Composes medicamenteux
US7402598B2 (en) 2002-07-25 2008-07-22 Glaxo Group Limited Arylethanolamine β2-adrenoreceptor agonist compounds
WO2004016578A2 (fr) * 2002-07-25 2004-02-26 Glaxo Group Limited Composes medicamenteux
WO2004037768A3 (fr) * 2002-10-28 2004-07-29 Glaxo Group Ltd Composes a usage medicinal
WO2004037768A2 (fr) * 2002-10-28 2004-05-06 Glaxo Group Limited Composes a usage medicinal
US7538127B2 (en) 2003-02-14 2009-05-26 Glaxo Group Limited Medicinal compounds
EP1719507A1 (fr) 2005-04-13 2006-11-08 Astion Development A/S Des agonistes de bêta-2 adrénocepteur pour le traitement de maladies du tissus conjonctifs
US8426475B2 (en) 2005-04-13 2013-04-23 Astion Development A/S Treatment of connective tissue diseases of the skin
US9907765B2 (en) 2005-04-13 2018-03-06 Cipher Pharmaceuticals Inc. Treatment of connective tissue diseases of the skin

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