US3657244A - 1-(2' 3' 4'-trisubstituted phenyl)-2-amino-alkanols-(1) and salts thereof - Google Patents

1-(2' 3' 4'-trisubstituted phenyl)-2-amino-alkanols-(1) and salts thereof Download PDF

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US3657244A
US3657244A US713265A US3657244DA US3657244A US 3657244 A US3657244 A US 3657244A US 713265 A US713265 A US 713265A US 3657244D A US3657244D A US 3657244DA US 3657244 A US3657244 A US 3657244A
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phenyl
methoxy
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hydrochloride
dihydroxy
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Anton Mentrup
Karl Zeile
Otto Thoma
Kurt Schromm
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CH Boehringer Sohn AG and Co KG
Boehringer Ingelheim GmbH
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline

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  • the compounds are 1-(2',3,4-trisubstituted-phenyl)-2- amino-alkanols-(l) and acid addition salts thereof, useful as sympathomimetics in warm-blooded animals.
  • This invention relates to novel 1-(2',3',4'-trisubstitutedphenyl)-2-secondary amino-alkanols-(l) and acid addition salts thereof, as well as to various methods of preparing these compounds.
  • the present invention relates to racemic mixtures of a novel class of compounds of the formula R10 R2 R3 ma-mun,
  • R is hydrogen or acyl
  • R is straight or branched alkyl of 1 to carbon atoms, stright or branched alkoxy of 1 to 5 carbon atoms, or cycloalkyl of 5 to 6 carbon atoms,
  • R is hydrogen or lower alkyl
  • R is straight or branched alkyl of l to 8 carbon atoms
  • Z is straight or branched alkylene of 2 to 6 carbon atoms
  • n 0 to 1
  • R and R which may be identical to or difierent from each other, are each hydrogen, hydroxyl, lower alkyl or lower alkoxy or, together with each other, methylenedioxy,
  • R is other than isopropyl when R is hydrogen, R is methyl or methoxy and R is hydrogen, methyl or ethyl; their stereoisomeric components; their diastereomeric antipodes; and non-toxic, pharmacologically acceptable acid addition salts of said racemic mixtures, stereoisomers or diastereomeric antipodes.
  • the compounds according to the present invention may be prepared by a number of different methods involving well known chemical principles, among which the following have proved to be particularly convenient and efficient:
  • R R and R have the same meanings as in Formula I; each R either has the same meanings as R; in Formula I or is a protective group which may subsequently be split off, preferably by hydrolysis or hydrogenation, such as acyl or benzyl; or both R, together with each other and the oxygen atoms to which they are attached, form an acetal group whose hydrocarbon moiety preferably contains the diphenylmethylene or cyclohexylidene group; and R is hydrogen or a protective group, such as benzyl.
  • the reduction may be carried out with the aid of hydrogen in the presence of a hydrogenation catalyst, such as Raney nickel, platinum or palladium; or also with the aid of complex hydrides, especially sodium borohydride or lithium aluminum hydride; or also by means of the Meerwein-Ponndorf-Verley Reduction.
  • a hydrogenation catalyst such as Raney nickel, platinum or palladium
  • complex hydrides especially sodium borohydride or lithium aluminum hydride
  • the various protective groups may be split off all at once or in stepwise fashion, during or after the reduction, by conventional methods.
  • a starting compound of the Formula II may be obtained by customary methods, such as by reacting a com pound of the formula 9 I am c crmgx m wherein R and K, have the same meanings as in Formula I, R has the same meanings as in Formula II, and X is chlorine, bromine or iodine, with an amine of the formula wherein R, has the same meanings as in Formula I and R" has the same meanings as in Formula II.
  • Method B By reducing a compound of the formula I R Q R2 9 mo n c R (V) wherein R and K, have the same meanings as in Formula I, R has the same meanings as in Formula II and R is C(') or CH(OH), in the presence of an amine of the formula H2NR4 (VI)
  • the reduction may be effected with hydrogen in the presence of a hydrogenation catalyst, such as Raney nickel or palladium, or with a complex hydride, such as lithium aluminum hydride or sodium borohydride.
  • each R in the starting compound of the Formula V is a protective group, especially benzyl, and these protective groups may be removed in customary fashion subsequent to the reduction reaction. If desired, in those cases where R, is CH(OH)-, the Schiffs base formed by the condensation reaction between compound V and amine VI may also be used as the starting compound.
  • a dicarbonyl compound of the Formula V may be obtained by customary methods, such as by oxidation of an analogously substituted aceto-, propio-, butyroor valerophenone with selenium oxide.
  • Method D By reacting an amine of the formula wherein R R and R have the same meanings as in Formula VIIa, under reducing conditions, with a compound of the formula $3 en cu ma wherein R is hydrogen or s traight-chain lower alkyl; R is straight or branched lower alkyl, the sum of the carbon atoms in R and R being no greater than 7; and R may further be 1,4 benzodioxan 2 yl, 1,4 benzodioxan 2-ylmethyl, 1,4-benzodioxan-2-ylethyl or wherein Z is lower alkylene, the sum of the carbon atoms in Z and R being no more than 5, and R R and n have the same meanings as in Formula Ia; and R and R together with each other, may also be alkylene of no more than 6 carbon atoms.
  • the reducing agent may be hydrogen in the presence of a hydrogenation catalyst, such as platinum. If R in Formula X is a protective group which may be split off by hydrogenation, these protective groups may simultaneously be split off. If R is acyl, these may be removed subsequent to the reduction in customary fashion, if desired.
  • a hydrogenation catalyst such as platinum.
  • a complex hydride such as sodium borohydride or lithium aluminum hydride, may also be used as the reducing agent. Under those conditions, it is preferred to use as the starting material a compound of the Formula IX wherein R is a protective group, especially benzyl or diphenylmethyl, and any protective groups present in the reaction product may subsequently be split off in customary fashion.
  • An amine of the Formula IX may be obtained by well known methods from an analogously substituted isonitrosoketone, cyanhydrin, benzoylcyanide, hydrazine, hydrazide, azidophenone or diazophenone.
  • an analogously substituted starting compound mentioned in the preceding sentence may be subjected, as such, to the reductive substitution reaction, whereby the amine IX is formed in situ and undergoes reaction with compound X.
  • R and K have the same meanings as in Formula I, R has the same meanings as in Formula II, and R; has the same meanings as in Formula V, preferably with a complex hydride, such as lithium aluminum hydride.
  • a complex hydride such as lithium aluminum hydride.
  • a carboxylic acid amide of the Formula XI wherein the hydroxyl groups in the 3- and 4-positions on the phenyl ring are protected in the form of acetal or benzylether groupings. These protective groups may be split off again subsequent to the reduction.
  • Method F By reacting a compound of the formula CH CH NHR" OH (XII) wherein R and R have the same meanings as in Formula I and R and R have the same meanings as in Formula II, with a compound of the formula R Y (XIII) wherein R, has the same meanings as in Formula I and Y is chlorine, bromine, iodine, arylsulfonyl or alkylsulfonyl.
  • R has the same meanings as in Formula I and Y is chlorine, bromine, iodine, arylsulfonyl or alkylsulfonyl.
  • the reaction is advantageously carried out in the presence of an acid-binding condensation agent, such as sodium carbonate or potassium carbonate; however, the amine XII may itself also serve as the acid-binding agent, provided it is present in suflicient excess over and above the stoiehiometrically required amount.
  • the protective groups may subsequently be removed in customary fashion.
  • the compounds of the Formula I are organic bases and therefore form acid addition salts with inorganic or organic acids.
  • non-toxic, pharmacologically acceptable acid addition salts are those formed with hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, tartaric acid, fumaric acid, maleic acid, ascorbic acid, benzoic acid, cyclohexylsulfarnic acid, 8-chlorotheophylline or the like.
  • an end product of the Formula I contains only one asymmetric carbon atom
  • a racemic mixture thereof may, if desired, be separated into its optical antipode components by conventional methods. If more than one center of asymmetry are present, the racemates of the diastereomeric pairs of antipodes may be separated from each other, and each pair may in turn be separated into the individual antipodes.
  • fractional crystallization of their addition salts formed with optically active acids such as dibenzoylor ditoluyl-a-tartaric acid.
  • raw 1-(2-ethoxy 3',4 diphenylmethylenedioxy-phenyl)-loxo-2-(benzyl-isopropylamino)-ethane 81 gm. of this raw base were dissolved in a mixture of 540 cc. of methanol and 270 cc. of water, the solution was purified by filtering it through animal charcoal, and the filtrate was hydrogenated in the presence of palladized charcoal.
  • the 1-(2'- ethoxy-3',4'-dihydroxypheny1) 1 oXo-2-isopropylaminoethane formed thereby was isolated as its hydrochloride, M.P. 3-205 C. (recrystallized from 95% isopropanol), with the aid of acetone.
  • the hydrochloride thus obtained was boiled for 90 minutes with 48% hydrobromic acid, yielding Ot-[Z-(P- hydroxy-phenyl)-isopropylamino]-2-methyl 3,4 dihydroxy-acetophenone hydrobromide, M.P. l l25 C., which was converted into the hydrochloride, MP. 120 135 C., by dissolving it in water and acidifying the solution with concentrated hydrochloric acid.
  • reaction solution was cooled to room temperature and was then diluted with ether, whereby N-benzyl-fl-phenoxyethyl-amine hydrobromide precipitated out, which was separated by vacuum filtration.
  • the benzene was distilled out of the filtrate in vacuo, the residue was dissolved in ethyl acetate, and the solution was acidified with ethereal hydrochloric acid, whereby a-(N-benzyl-B-phenoxyethylamine)-2-methoxy 3,4 diphenylmethylenedioxy-acetophenone hydrochloride crystallized out, which was recrystallized from a mixture of methylenechloride and ethyl acetate, whereupon it had a melting point of 159-161 C.
  • the hydrochloride thus obtained was converted into the free base a-(fi-phenoxyethyl-amino)-2-methoxy-3,4- dihydroxy-acetophenone with concentrated aqueous ammonia, the free base was dissolved in methanol, and the solution was hydrogenated at standard temperature and pressure in the presence of Raney nickel as a catalyst until substantially the theoretical amount of hydrogen had been absorbed. Thereafter, the catalyst was filtered off, the filtrate was evaporated in vacuo in a stream of nitrogen, the residue was dissolved in acetone, and the solution was acidified with ethereal hydrochloric acid.
  • the amino-acetophenone salt thus obtained was dissolved in methanol, and the solution was hydrogenated at standard temperature and pressure with platinum as a catalyst until substantially the theoretical amount of hydrogen had been absorbed. Thereafter, the catalyst was filtered off, the methanol was distilled out of the filtrate in vacuo, and the oily residue was allowed to stand with a mixture of isopropanol and ethyl acetate, whereby it became crystalline.
  • the crystalline substance was recrystallized from acetonitrile, yielding 1-(2'-methoxy-3,4'-dihydroxy-phenyl) 2 (B-p-tolyloxyethyl-amino)-ethanol- (l) hydrochloride, M.P.
  • EXAMPLE 13 Using a procedure analogous to that described in Example 8, 1-(2'-methoxy-3',4'-dihydroxy-phenyl) 2 [(oc,- a-dimethyl-y-p-tolyl-n-propyl) amino] ethanol (l) hydrochloride, M.P. 168-170 C. (recrystallized from ethanol/ether), was prepared from a-[(u',a'-dimethyl-'y'- p-tolyl-n-propyl)-amino] 2 methoxy-3,4-dihydroxyacetophenone hydrochloride (M.P. 166-167 C.).
  • EXAMPLE 14 Preparation of 1-(2-methyl-3',4'-dihydroxy-phenyl)-2- tert. butylamino-ethanol-(l) by method A A mixture consisting of 31 gm. of a-bromo-2-methyl- 3,4-di-benzyloxy-acetophenone (M.P. 123 C.), 155 cc. of benzene and 27 gm. of tert, butylarnine was stirred for two hours at 40-50 C.
  • M.P. 123 C. a-bromo-2-methyl- 3,4-di-benzyloxy-acetophenone
  • 155 cc. of benzene and 27 gm. of tert, butylarnine was stirred for two hours at 40-50 C.
  • reaction mixture was extracted with water, the aqueous extract solution was discarded, the benzene solution was evaporated, the residue was dissolved in acetonitrile, and the solution was acidified with etheral hydrochloric acid, yielding atert. butylamino-2-methyl-3,4-di-benzyloxy-acetophenone hydrochloride, M.P. 199-204 C.
  • the hydrochloride thus obtained was converted into the free base by treating it with aqueous ammonia, extracting the alkaline aqueous mixture with ether, and evaporating the ethereal solution.
  • 16 gm. of the free base were dissolved in 100 cc. of ethanol, 0.73 gm. of sodium borohydride was added thereto, and the mixture was allowed to stand at room temperature for 12 hours. Thereafter, the reaction mixture was evaporated, the residue was decomposed with water, the aqueous mixture was extracted with ether, the ethereal extract solution was evaporated, and the residue was recrystallized from petroleum ether, yielding crystalline l (2 methyl 3',4'-di-benbyloxyphenyl) 2 tert. butylamino-ethanol-(l), M.P. 111- 112 C.
  • the compounds according to the present invention that is, racemic mixtures of those embraced by Formula I, their pure stereoisomers, diasteromeric antipode pairs thereof, and non-toxic, pharmacologically acceptable acid addition salts of any of these, have useful pharmacodynamic properties. More particularly, they exhibit sympathomimetic activities in warm-blooded animals, such as mice and rats; especially, they exhibit bronchospasmolytic and antipuritic activities and dilate the peripheral 13 blood vessels in warm-blooded animals, such as those above referred to.
  • R is methoxy, ethoxy, methyl, ethyl or propyl
  • R is hydrogen, methyl or ethyl
  • R is alkyl of up to 8 carbon atoms, cycloalkyl of 5 to 6 carbon atoms or a substituent of the Formula Ia where Z is alkylene of 2 to 5 carbon atoms, and R and R are each hydrogen, hydroxyl, methyl or methoxy.
  • the compounds of the present invention are administered to warm-blooded animals topically, perorally or parenterally as active ingredients in customary dosage unit compositions, that is compositions in dosage unit form consisting essentially of an inert pharmaceutical carrier and one effective dosage unit of the active ingredient, such as sprays, tablets, coated pills, granulates, suppositories, ointments, solutions or suspensions.
  • One eifective dosage unit of a compound according to the present invention is from 0.1 to 10.0 mgm./ kg. body weight.
  • EXAMPLE 18 Tablets The tablets are compounded from the following in- Compounding procedure
  • the t1-(2-ethoxy-3',4'-dihydroxy-phenyl)-1-hydroxy-2- isopropylamino-ethane hydrochloride is thoroughly admixed with the lactose, 25.0 parts of the corn starch and 4.0 parts of the SiO and the resulting mixture is uniformly moistened with a 5% ethanolic solution of the polyvinyl pyrrolidone.
  • the moist mass is then passed through a 1 mm. mesh screen.
  • the resulting granulate is dried for about 24 hours at 60 C. in a drying chamber with fresh air circulation.
  • the dry granulate is again passed through a 1 mm. mesh screen.
  • EXAMPLE 19 2% inhalation solution This solution is packaged in m1. bottles, the contents of each bottle being composed of the following ingredients:
  • EXAMPLE 22 Starch capsules for peroral administration The contents of the capsules are compounded from the following ingredients:
  • Z is alkylene of 2 to 6 carbon atoms, and R and R are each hydrogen or lower alkyl;
  • a racemic mixture of a compound of the formula R is hydrogen or alkyl of 1 to 3 carbon atoms, Z is alkylene of 2 to 6 carbon atoms, and R and R are each hydrogen or lower alkyl;
  • a compound according to claim 1 which is a racemic mixture of 1-(2-methoxy 3',4 dihydroxy-phenyl)-2- 16 [(a,a-dimethyl-' -p-stereoisomer thereof, or a non-toxic, pharmacologically acceptable acid addition salt of said racemic mixture or stereoisorner.
  • a compound according to claim 2 which is a racemic mixture of 1-(2'-methoxy 3',4 dihydroxy-phenyl)-2- a,u-dimethyl-'y-phenyl-n-propyl)-amino] -ethanol-( 1 a pure stereoisomer thereof, or a non-toxic, pharmacologically acceptable acid addition salt of said racemic mixture or stereoisomer.

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US713265A 1966-10-18 1967-10-16 1-(2' 3' 4'-trisubstituted phenyl)-2-amino-alkanols-(1) and salts thereof Expired - Lifetime US3657244A (en)

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Cited By (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3868461A (en) * 1972-11-22 1975-02-25 Interx Research Corp Ester of 3,4-dihydroxy-alpha (isopropylamino) methyl benzyl alcohol, composition and anti-asthma use thereof
US3908017A (en) * 1973-04-26 1975-09-23 Interx Research Corp Sympathomimetic compositions containing an ester of -3-hydroxy-{60 -{8 (methylamino)methyl{8 benzyl alcohol and methods of use
US3969410A (en) * 1972-01-12 1976-07-13 Boehringer Ingelheim Gmbh 1-(2'-Alkyl-3',4'-dihydroxy-phenyl)-2-(phenylalkyl-amino)-alkanols-(1) and salts thereof
US4042713A (en) * 1966-10-18 1977-08-16 Boehringer Ingelheim Gmbh Pharmaceutical compositions containing a 1-(2-alkyl-3,4-dihydroxy-phenyl)-2-(phenylalkyl-amino)-alkanol-(1) and method of use
US4046913A (en) * 1973-08-18 1977-09-06 Boehringer Ingelheim Gmbh 1-(M-alkanoyloxy-phenyl)-1-hydroxy-2-(N-lower alkyl-amino)-ethanes and salts thereof
US4094983A (en) * 1977-01-17 1978-06-13 Interx Research Corporation Method for reducing intraocular pressure in warm-blooded animals
US4115585A (en) * 1976-05-17 1978-09-19 Instituto Luso Farmaco D'italia S.R.L. Esters of 1-(p-hydroxyphenyl)-2-(1'-methyl-2'-phenoxyethylamino)-1-propanol
US4138581A (en) * 1969-04-01 1979-02-06 Sterling Drugs Inc. 3(Hydroxy or hydroxymethyl)-4(hydroxy)-α-(aminomethyl)benzyl alcohols
US4147799A (en) * 1971-06-24 1979-04-03 Kyowa Hakko Kogyo Co., Ltd. Process for reducing blood pressure and blocking β-adrenergic receptor
US4192805A (en) * 1975-11-27 1980-03-11 Nicholas International Limited Process of preparing amino ethanols
US4275074A (en) * 1979-03-09 1981-06-23 Graham J. Dobbie Catecholamine treatment of ocular hypertension
US4287212A (en) * 1976-04-30 1981-09-01 American Hoechst Corporation 2-Aryl-1,2-dialkylcycloalkylamines
US4324800A (en) * 1980-03-28 1982-04-13 Tanabe Seiyaku Co., Ltd. Novel benzylalcohol derivatives and processes for preparing same
US4336400A (en) * 1969-04-01 1982-06-22 Sterling Drug Inc. 3-(Hydroxy or hydroxymethyl)-4-hydroxy-alpha(aminomethyl)benzyl alcohols and methods of use
WO1982003327A1 (en) * 1981-04-01 1982-10-14 Maurice E Langham Compounds and compositions for treatment of ocular hypertension
US4450115A (en) * 1979-03-20 1984-05-22 Kyowa Hakko Kogyo Co., Ltd. Amino-alcohol derivatives
US4461914A (en) * 1983-02-01 1984-07-24 American Cyanamid Company Method for the preparation of 1-(4'-amino-3',5'-dichlorophenyl)-2-alkyl(or dialkyl)aminoethanols
US4535159A (en) * 1981-05-13 1985-08-13 Ferrer Internacional, S.A. Process for producing 1-position amino-derivatives of 1-(3',4'-methylenedioxyphenyl)propane-2-ol
US4699928A (en) * 1984-07-13 1987-10-13 Merrell Dow Pharmaceuticals Inc. Fluoroallylamine derivatives
US4843160A (en) * 1984-10-01 1989-06-27 The Dow Chemical Company Preparation of alpha-aminoalkylphenols
US4990505A (en) * 1984-04-17 1991-02-05 Glaxo Group Limited Phenethanolamine compounds
US5063246A (en) * 1980-07-29 1991-11-05 Yamanouchi Pharmaceutical Co., Ltd. Phenethylamine derivative compositions and use
US5068432A (en) * 1988-03-30 1991-11-26 Aldrich Chemical Company, Inc. Process for producing optically pure 2-phenoxyphenylalkylamines
US20040122108A1 (en) * 2002-10-04 2004-06-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg Betamimetics with a prolonged duration of activity, processes for preparing them, and their use as pharmaceutical compositions
US20040138307A1 (en) * 2002-11-15 2004-07-15 Boehringer Ingelheim Pharma Gmbh & Co. Kg Dihydroxymethylphenyl derivatives, processes for preparing them, and their use as pharmaceuticals
CN110743544A (zh) * 2019-11-07 2020-02-04 西安凯立新材料股份有限公司 一种苯乙酮选择加氢制备α-苯乙醇用钯炭催化剂及其制备方法与应用

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DE1962497C3 (de) * 1969-12-12 1979-09-20 C.H. Boehringer Sohn, 6507 Ingelheim Naphthylalkyl- a -hydroxyphenäthyl-amine, ihre Herstellung und diese enthaltende Arzneimittel
ATE7689T1 (de) 1980-07-09 1984-06-15 Aktiebolaget Draco 1-(dihydroxyphenyl)-2-amino-aethanol-derivate, verfahren und mittel zu ihrer herstellung sowie diese derivate enthaltende mittel.
US4472427A (en) * 1980-12-23 1984-09-18 Merck & Co., Inc. (Aralkylamino-2-OR-propoxy)heterocyclic compounds
JPH02124884A (ja) * 1988-07-08 1990-05-14 Zhongguo Yixuekexueyuan Yaowo Yanjiusuo Ｎ―置換アミド誘導体
DE10246374A1 (de) * 2002-10-04 2004-04-15 Boehringer Ingelheim Pharma Gmbh & Co. Kg Neue Betamimetika mit verlängerter Wirkungsdauer, Verfahren zu deren Herstellung und deren Verwendung als Arzneimittel

Cited By (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4042713A (en) * 1966-10-18 1977-08-16 Boehringer Ingelheim Gmbh Pharmaceutical compositions containing a 1-(2-alkyl-3,4-dihydroxy-phenyl)-2-(phenylalkyl-amino)-alkanol-(1) and method of use
US4138581A (en) * 1969-04-01 1979-02-06 Sterling Drugs Inc. 3(Hydroxy or hydroxymethyl)-4(hydroxy)-α-(aminomethyl)benzyl alcohols
US4336400A (en) * 1969-04-01 1982-06-22 Sterling Drug Inc. 3-(Hydroxy or hydroxymethyl)-4-hydroxy-alpha(aminomethyl)benzyl alcohols and methods of use
US4147799A (en) * 1971-06-24 1979-04-03 Kyowa Hakko Kogyo Co., Ltd. Process for reducing blood pressure and blocking β-adrenergic receptor
US3969410A (en) * 1972-01-12 1976-07-13 Boehringer Ingelheim Gmbh 1-(2'-Alkyl-3',4'-dihydroxy-phenyl)-2-(phenylalkyl-amino)-alkanols-(1) and salts thereof
US3868461A (en) * 1972-11-22 1975-02-25 Interx Research Corp Ester of 3,4-dihydroxy-alpha (isopropylamino) methyl benzyl alcohol, composition and anti-asthma use thereof
US3908017A (en) * 1973-04-26 1975-09-23 Interx Research Corp Sympathomimetic compositions containing an ester of -3-hydroxy-{60 -{8 (methylamino)methyl{8 benzyl alcohol and methods of use
US4046913A (en) * 1973-08-18 1977-09-06 Boehringer Ingelheim Gmbh 1-(M-alkanoyloxy-phenyl)-1-hydroxy-2-(N-lower alkyl-amino)-ethanes and salts thereof
US4192805A (en) * 1975-11-27 1980-03-11 Nicholas International Limited Process of preparing amino ethanols
US4287212A (en) * 1976-04-30 1981-09-01 American Hoechst Corporation 2-Aryl-1,2-dialkylcycloalkylamines
US4115585A (en) * 1976-05-17 1978-09-19 Instituto Luso Farmaco D'italia S.R.L. Esters of 1-(p-hydroxyphenyl)-2-(1'-methyl-2'-phenoxyethylamino)-1-propanol
US4094983A (en) * 1977-01-17 1978-06-13 Interx Research Corporation Method for reducing intraocular pressure in warm-blooded animals
US4275074A (en) * 1979-03-09 1981-06-23 Graham J. Dobbie Catecholamine treatment of ocular hypertension
US4590210A (en) * 1979-03-09 1986-05-20 Langham Maurice E Compositions for treatment of ocular hypertension
US4450115A (en) * 1979-03-20 1984-05-22 Kyowa Hakko Kogyo Co., Ltd. Amino-alcohol derivatives
US4324800A (en) * 1980-03-28 1982-04-13 Tanabe Seiyaku Co., Ltd. Novel benzylalcohol derivatives and processes for preparing same
US5063246A (en) * 1980-07-29 1991-11-05 Yamanouchi Pharmaceutical Co., Ltd. Phenethylamine derivative compositions and use
WO1982003327A1 (en) * 1981-04-01 1982-10-14 Maurice E Langham Compounds and compositions for treatment of ocular hypertension
US4535159A (en) * 1981-05-13 1985-08-13 Ferrer Internacional, S.A. Process for producing 1-position amino-derivatives of 1-(3',4'-methylenedioxyphenyl)propane-2-ol
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ES360964A1 (es) 1970-10-16
NL158480B (nl) 1978-11-15
ES360962A1 (es) 1970-11-16
SE380792B (sv) 1975-11-17
AT288357B (de) 1971-03-10
DE1543374B2 (de) 1973-02-22
CH523219A (de) 1972-05-31
DK130070B (da) 1974-12-16
DE1543374A1 (de) 1972-04-20
NL6714161A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1968-04-19
ES360965A1 (es) 1970-11-16
CH490323A (de) 1970-05-15
DK130070C (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1975-05-26
DE1543374C3 (de) 1973-10-04
DE1543372A1 (de) 1971-04-01
ES346057A1 (es) 1969-03-16
ES360963A1 (es) 1970-11-16
SE368196B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1974-06-24
CH548365A (de) 1974-04-30
ES360961A1 (es) 1970-11-16
GB1204195A (en) 1970-09-03
FR7338M (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1969-10-13
BE705312A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) 1968-04-18
CH507200A (de) 1971-05-15
AT285582B (de) 1970-11-10
AT288358B (de) 1971-03-10

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