US3205136A - Antidepressant phenyloxyalkylamines - Google Patents

Antidepressant phenyloxyalkylamines Download PDF

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Publication number
US3205136A
US3205136A US246672A US24667262A US3205136A US 3205136 A US3205136 A US 3205136A US 246672 A US246672 A US 246672A US 24667262 A US24667262 A US 24667262A US 3205136 A US3205136 A US 3205136A
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ether
solution
toluene
mixture
dimethyl
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US246672A
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David H Tedeschi
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Smith Kline and French Laboratories Ltd
SmithKline Beecham Corp
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Smith Kline and French Laboratories Ltd
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Priority to US246672A priority Critical patent/US3205136A/en
Priority to GB46923/63A priority patent/GB1014348A/en
Priority to BE640617A priority patent/BE640617A/xx
Priority to FR955689A priority patent/FR3075M/fr
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Assigned to SMITHKLINE BECKMAN CORPORATION reassignment SMITHKLINE BECKMAN CORPORATION CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). EFFECTIVE DATE: 03/04/82 Assignors: SMITHKLINE CORPORATION
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • 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

Definitions

  • novel compositions of this invention have a pharmacological profile strikingly similar to that of imipramine, a known antidepressant, but comprise as the active ingredient a compound of unrelated chemical structure.
  • a prominent pharmacological property of these compositions is their ability to prevent reserpine induced ptosis in rats. This pharmacological procedure is especially useful to characterize the antidepressant activity of irnipr-amine.
  • compositions of this invention do not inhibit monoamine oxidase activity in vivo. These compositions are further characterized by relative freedom from side effects, a rapid onset of: action and effectiveness in both mild and severe depression.
  • compositions of this invention comprise in dosage unit form a nontoxic pharmaceutical carrier and a phenoxyalkylamine or" the following formula:
  • R and R represent hydrogen, chlorine, bromine, lower alkvl of one to four carbon atoms, lower allcoxy of one to four carbon atoms or trifluoromethyl;
  • X represents the divalent group R represents hydrogen or methyl
  • R represents methyl or, when taken together with R forms with the nitrogen to which they are attached a pyrrolidine or piperidine ring.
  • a preferred composition in accordance with this invention comprises the compound N,Ndirnethyl-2-(2,6-dichlorophenoxy)propylarnine.
  • the nontoxic pharmaceutically acceptable acid addition salts of the compounds of the aboveforrnula are also included within the scope of this invention since such salts are likewise effective for producing antidepressant activity.
  • Both organic and inorganic acids can be employed-to form pharmaceutically acceptable salts, illustrative acids ein-g sulfuric, nitric, phosphoric hydrochloric, citric, acetic, lactic, tartaric, ethanedisulfonic, sulfamic, sucoinic, fumaric, maleic, benzoic and the like. prepared by methods known to the art.
  • compositions of this invention comprise a phen-oxyalkylamine of Formula I in an amount sufficient to produce antidepressant activity.
  • compositions contain firom about mg. to about 500 mg. of medicament, advantageously from about 25 mg. to about 400 mg. per dosage unit.
  • the pharmaceutical carrier employed in the composition can be either a sol-id or liquid.
  • exemplary of solid carriers are lactose, magnesium stearate, terra alba, sucrose, talc, ste-aric acid, gelatin, agar pectin or acacia.
  • liquid carriers are peanut oil, olive oil, sesame oil and Water.
  • the carnier or diluent may include a time delay material such as glyceryl monos-teara'te or glyceryl distearate alone or with a wax.
  • compositions can be ta-blotted, used as a pharmaceutical powder, placed in a hard gelatin capsule or in the form of a troch or lozenge.
  • a liquid carrier is used the composition can be in the form of a soft gelatin capsule or a liquid suspension.
  • Parenteral dosage for-ms are obtained by dis-solving a water soluble snt of the active medicament in water or saline solution in a concentration such that 1 cc. of the solution contains from about 10 mg. to about 50 mg. of active medicament. The solution can then be filled into single or multiple dose ampules.
  • the method for using the compositions in accordance wit-h this invention comprises administering internally to animals, including human beings, a phenoxyalky-la-mine of Formula I or a nontoxic organic or inorganic acid addition salt thereof, preferably with a nontoxic pharmaceutical carrier such as described above, in an amount sufiicient to produce antidepressant activity.
  • the compositions are administered to treat both mild and severe depression as exhibited by mildly depressed outpatients and more severely disturbed and hospitalized depressed patients, respectively.
  • the active medicament in dosage units as described above is administered orally or parenter-ally in repeated doses in a range of from about 10 mg. .to about 1500 mg. daily. In mild depression, the daily dosage is from about 10 mg. to about 250 mg. of active medicament, advantageously from about mg. to about 250 mg. In severe depression, the daily dosage is from about250 mg. to about 1500 mg. of active medicament, advantageously from about 250 mg. to about 1200 mg. -When the methods described above are carried out, antidepressant activity is produced
  • the compounds of Formula I above which form the active medicament in the pharmaceutical compositions and are useful in the method of this invention are prepared by the following general procedure.
  • the appropriate phenol (as the sodium salt) is condensed with the aminoalkyl halide to give the product directly or alternatively condensed with an a-haloaminoalkylamide and the resultant phenoxyamide reduced with for example lithium aluminum hydride to the alkylamine.
  • Example 1 To a suspension of 1.9 g. of sodium hydride in ml. of dry toluene is rapidly added a solution of 8.8 g. of 2,6- dimethylphenol in ml. of dry toluene. The mixture is stirred at reflux for one hour, then cooled in an ice bath while a solution of 15 g. of N,N-dimethyl-ot-bromopropionamide (prepared from the reaction of u-bromopropionyl bromide and dimethylamine) is added. The mixture is stirred at reflux for 12 hours and then filtered. The filtrate is washed with 10 percent sodium hydroxide solution and then with water, dried over magnesium sul fate and concentrated under reduced pressure. The resi due is distilled at llOl23 C./ 0.6-0.8 mm. to give N,N- dimethyl-a-(2,6-dimethylphenoxy)propionamide.
  • Example 2 Using the same procedure as in Example 1, 2.6 g. of sodium hydride, 16.3 g. of 2,6-dichlorophenol and 21.1 g. of N,N-dimethyl-oc-bromopropionamide are reacted to yield N,N-dimethyl a (2,6 dichlorophenoxy)propionamide.
  • Example 3 A solution of 22.5 g. of anhydrous dimethylamine in 26.3 g. of formic acid and 50 g. of 2,6-dichlorophenoxyacetone (prepared from the reaction of 2,6-dichlorophenol and chloroacetone) is heated at a reaction temperature of 120-125 C. until the evolution of carbon dioxide almost ceases. The mixture is cooled to room temperature and made acidic with dilute hydrochloric acid. The aqueous layer is separated, washed with ether, made alkaline with sodium hydroxide and the amine taken up with ether. After drying over potassium carbonate the ether is removed by evaporation and the oily residue is distilled at 9091 C./O.25 mm. to give a yelow oil, 2-(2,6-dichlorophenoxy)-N,N-1-trimethylethylamine.
  • 2,6-dichlorophenoxyacetone prepared from the reaction of 2,6-dichlorophenol and chloroacetone
  • Example 4 A dry toluene solution of fl-dimethylaminoethyl chloride is prepared by trituration of 144.1 g. of the amine hydrochloride in toluene with large excess of potassium hydroxide pellets.
  • 2,6-dichlorophenol (81.5 g.) in 300 ml. of dry toluene is added slowly to a stirred suspension of 12.5 g. of sodium hydride in 200 ml. of toluene over a period of 20 minutes. The mixture is stirred at reflux for one hour and cooled. The toluene solution of fi-dimethylaminoethyl chloride is added dropwise over a period of one hour and the well-stirred mixture is refluxed for eight hours. After cooling to room temperature the mixture is treated with 150 ml. of water followed by 250 ml. of 3 M hydrochloric acid. The toluene layer is separated and extracted with 250 ml. of 3 M hydrochloric acid.
  • the combined aqueous acid solution is extracted with ether and then made basic with 40% sodium hydroxide.
  • the amine is taken up with ether and the aqueous layer is extracted several times with ether.
  • the combined ether solution is extracted once with water, dried over potassium carbonate, and evaporated.
  • the amber residue is i distilled at -92 C./ 0.8-0.9 mm. to give N,N-dimethyl- 2-(2,6-dichlorophenoxy)ethylamine.
  • Example 5 To a stirred suspension of 2.9 g. of sodium hydride in 75 ml. of sodium-dried toluene is added a solution of 13.6 g. of 2,6-dirnethylphenol in ml. of dry toluene over a 20 minute period. The mixture is stirred at reflux for one hour and cooled. A toluene solution of Z-dimethylaminopropylchloride, which is prepared by it-riturating 35.4 g. of 3-dimethylaminopropylchl-oride hydrochloride with an excess of potassium hydroxide pellets under toluene, is added over a one hour period. Reflux is resumed and continued for eight hours.
  • Example 6 To a stirred suspension of 4.7 g. of sodium hydride in ml. of sodium-dried toluene is added a solution of 25.1 g. of 2,4-dich-lorophenol in 180 ml. of dry toluene over a 15 minute period. The mixture is stirred at reflux for 55 minutes, then cooled in an ice bath during the 15 minute addition of -a toluene solution of ,B-dimethylaminoethyl chloride, prepared by tritura'ting 46 g. of B-dimethylaminoe thyl chloride hydrochloride with potassium hydroxide pellets under toluene. After an eight hour period of stirring at reflux the mixture is cooled and 50 ml.
  • Example 7 To a stirred suspension of 7.5 g. of sodium hydride in 350 ml. of sodium-dried toluene is added a solution of 50 g. of 2,6-diisopropylphenol in 200 ml. of dried toluene over la 30 minute period. The mixture is stirred for one hour at 25 C. and for 70 minutes at refl x temperature. To the cooled mixture is added a toluene solution of B- dimethylaminoe'thyl chloride (prepared by triturating g. of fi dimethylaminoethyl chloride hydrochloride with excess potassium hydroxide pellets under toluene) during a 20 minute period. Reflux is resumed and continued for 12 hours.
  • B- dimethylaminoe'thyl chloride prepared by triturating g. of fi dimethylaminoethyl chloride hydrochloride with excess potassium hydroxide pellets under toluene
  • Example 8 To a stirred suspension of 2.9 g. of sodium hydride in 70 ml. of sodium-dried toluene is added -a solution of 25.2 g. of 2,6-di'bromophenol in 70 ml. of dry toluene over a minute period. The mixture is stirred at reflux temperature for 55 minutes, then cooled in an ice bath While a toluene solution of B-dimethylaminoethyl chloride, which had been prepared by triturating 28.8 g. of B-dimethylaminoethyl chloride hydrochloride with potassium hydroxide pellets under toluene, is added over a minute period.
  • Ethereal hydrochloric acid is added to an ethereal solution of a sample of this oil.
  • the hydrochloride salt is recrystallized from isopropanol-eth-er to give white crystals, MJP. 201-203.5 C.
  • Example 9 Following the general procedure of Example 4, the sodium 2,6-dichlorophenoxide (18.5 g.) prepared from sodium hydride and 2,6-dichlor'ophenol is reacted with 20.4 g. of N-(B-chloroethyDpyrrolidine freshly liberated in toluene to give upon workup an oily residue which is distilled to give N-[2-(2,6-dichlorophenoxy)ethyl1pyrrolidine, BF. 118'122 'C./0.15 mm.; hydrochloride salt, MJP. 181.5- 182.5 C.
  • Example 10 Similarly following the general procedure of Example 4, the sodium 2,6-dichlorophenoxide (18.5 g.) prepared from sodium hydride and 2,6-dichlorophenol is reacted with 22.3 g. of N-(fi-chloroethyl)piperidine freshly liberated in toluene to give upon workup an oily residue which is distilled to give N-[2-(2,6-dichlorophenoxy)ethylJpiperidine, RP. 121l24 C./ 0.15 mm.; hydrochloride salt, M.P. 185-186 C.
  • Example 11 A solution of 18.9 g. of N,N-dimethyl-2-(2,6-dichlorophenoxy)propylamine (prepared as in Example 2) in 75 ml. of benzene is added over a two hour period to a solution of 12.1 g. of cyanogen bromide in 100 ml. of benzene, at 5055 C. The reaction mixture is heated at this temperature for two hours and then allowed to stand for 18 hours. The solution is extracted with dilute hydrochloric acid and then washed with water. The benzene is removed in vacuo and the residue is hydrolyzed for 24 hours with 14.6 g. of sodium hydroxide and 175 ml. of 65% ethanol.
  • Example 12 Following the general procedure of Example 4, the sodium 3,5-hist-rifluoromethylphenoxide prepared from 12.0 g. of 3,5-bis-trifiuoromethylphenol and 2.6 g. of sodium hydride is reacted with 8.45 g. of N,N-dimethylaminoethyl chloride in 300 ml. of toluene. Working up the reaction mixture yields N,N-dimethyl-2-(3,5-bis-trifluoromethylphenoxy)ethylamine, B.P. 110 C./2l mm. The hydrochloride salt recrystallized from acetone melts at 193193.5 C.
  • Example 14 To a stirred suspension of 8.4 g. of sodium hydride in 300 ml. of anhydrous toluene is added a solution of 50 g. of 2,6-dimethoxyphenol in 200 ml. of anhydrous toluene and the mixture is stirred and refluxed for two and onehalf hours. The reaction mixture cooled in an ice-bath is treated slowly with N,N-dimethylaminoethyl chloride freshly liberated from 144 g. of its hydrochloride with potassium hydroxide pellets under toluene. Refluxing is resumed for 12 hours and then the reaction mixture is cooled in an ice-bath while 100 ml. of water and 85 ml.
  • Example 1 5 To a mixture of 26.6 g. of lithium aluminum hydride in 700 ml. of ether is added over a period of one hour a solution of 80 g. of N,N-dimethyl-a-(2-chloro)phenoxypropionamide. The resulting mixture is stirred for two days at room temperature and the excess hydride then destroyed by careful addition of 25 ml. of water, 50 ml. of 10% sodium hydroxide solution and 25 ml. of water. The mixture is stirred for one hour and filtered. The dried ethereal filtrate is evaporated and the residue distilled in vacuo to give N,N-dimethyl-2-(2-chlorophenoxy)propylamine, B.P. C./1.0 mm. Hydrochloride salt, MP. l34.5- 136 C.
  • Example 16 To a mixture of 19.7 g. of lithium aluminum hydride in 700 ml. of ether is added a solution of 50 g. of N,N- dimethyl-2-phenoxypropionamide in two liters of ether over a period of one hour. The resulting mixture is stirred at room temperature for three days and then treated cautiously with 25 ml. of water, 50 ml. of 10% sodium hydride solution and 25 ml. of water. This mixture is stirred for one hour, filtered and the dried filtrate evaporated. The residue is distilled in vacuo to give N,N-dimethyl-Z-phenoxypropylamine, B.P. 5459 C./0.50.6 mm. Hydrochloride salt, M.P. 146147 C.
  • the above ingredients are screened, mixed and filled into #2 hard gelatin capsules.
  • a method of producing antidepressant activity in animals and humans which comprises internally administering to said animals and humans a non-toxic out eifective amount of a compound selected from the group consisting of a phenoxyalkylamine and a nontoxic pharmaceutically acceptable acid addition salt thereof, said phenoxy allqylamine having the following formula:
  • R and R are members selected from the group consisting of hydrogen, chlorine, bromine, lower alkyl of from one to four carbon atoms, lower alkoxy of from one to four carbon atoms and trifiuoromethyl;
  • X is an alkylene group selected from the group consisting of CH3 CH3 R is a member selected from the group consisting of hydrogen and methyl;
  • R is a member selected from the group consisting of methyl and, when taken together with R and the nitrogen to which they are attached, a pyrrolidine and a piperidine ring.
  • a method of producing antidepressant activity in animals and humans which comprises internally administering to said animals and humans a daily dosage of from about 10 mg. to about 250 mg. of an antidepressant selected from the group consisting of a phenoxyalkylamine and a nontoxic pharmaceutically acceptable acid addition salt thereof, said phenoxyalkylamine having the following formula:
  • R and R are members selected from the group consisting of hydrogen, chlorine, bromine, lower alkyl of from one to four carbon atoms, lower alkoxy of from one to four carbon atoms and tritiuoromethyl;
  • X is an alkylene group selected from the group consisting of -CHgCH (3HCH2, -CHZCH and CH2CHgCI'Iz- CH3 CIIQ
  • R is a member selected from the group consisting of hydrogen and methyl; and R is a member selected from the group consisting of methyl and, when taken together with R and the nitrogen to which they are attached, a pyrrolidine and a piperidine ring.
  • a method of producing antidepressant activity in animals and humans which comprises internally adminis- 90 tering to said animals and humans a daily dosage of from about 250 mg. to about 1500 mg. of an antidepressant selected from the roup consisting of a phenoxyalkylamine and a nontoxic pharmaceutically acceptable acid addition salt thereof, said phenoxyalkylamine having the following formula:
  • R and R are members selected from the group consisting of hydrogen, chlorine, bromine, lower alkyl of from one to four carbon atoms, lower alkoxy of from one to four carbon atoms and trifiuoromethyl;
  • X is an alkylene group selected from the group consisting of -o1I oHi-, -CI-ICHZ, -CI I GII and CII2CH2CH1 H3 CH3 administered.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pyrrole Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
US246672A 1962-12-24 1962-12-24 Antidepressant phenyloxyalkylamines Expired - Lifetime US3205136A (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US246672A US3205136A (en) 1962-12-24 1962-12-24 Antidepressant phenyloxyalkylamines
GB46923/63A GB1014348A (en) 1962-12-24 1963-11-27 Antidepressant compositions comprising phenoxyalkylamines
BE640617A BE640617A (en:Method) 1962-12-24 1963-11-29
FR955689A FR3075M (fr) 1962-12-24 1963-12-02 Médicament agissant contre les troubles dus a une dépression, a base de phénoxy-alcoylamine.

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Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3515741A (en) * 1964-04-20 1970-06-02 Boehringer Sohn Ingelheim 1-cyanophenoxy-2-amino-alkanes
US3538228A (en) * 1966-06-03 1970-11-03 Ciba Ltd Pharmaceutical preparations comprising sulphur-containing amino-compounds for the treatment of depressive conditions and methods therefor
US4059621A (en) * 1972-07-21 1977-11-22 Science Union Et Cie, Societe Francaise De Recherche Medicale Substituted benzamido propanolamines
US4105796A (en) * 1975-06-02 1978-08-08 Boehringer Ingelheim Gmbh Pharmaceutical compositions containing racemic or optically active 1-(2,6-dimethyl-phenoxy)-2-methylamino-propane and method of use
US4218472A (en) * 1977-08-05 1980-08-19 Ab Kabi Geminally disubstituted indene derivatives
US4795758A (en) * 1986-02-10 1989-01-03 Societe A Responsabilite Limitee: Institut De Recherches Chimiques Et Biologiques Appliquees (I.R.C.E.B.A.) 5-[2-(pyrrolidin-1-yl)ethoxy]-p-cymene derivatives, the process for the preparation of the said derivatives and drugs in which the said derivatives are present
US4922021A (en) * 1981-03-04 1990-05-01 Basf Aktiensellschaft New alkylene diamine derivatives
WO1997015548A1 (en) * 1995-10-27 1997-05-01 Astra Aktiebolag New [(3-alkoxy-phenoxy)-ethyl]-dialkylamine derivatives and their use as local anaesthetics

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE761623A (fr) * 1970-04-15 1971-06-16 Recordati Chem Pharm Nouvelles phenoxyethylamines substituees therapeutiquement actives et procede pour leur preparation
ZA855101B (en) * 1984-07-13 1986-05-28 Merrell Dow Pharma Fluoroallylaine derivatives
GB0004152D0 (en) 2000-02-23 2000-04-12 Astrazeneca Uk Ltd Novel compounds
GB0004153D0 (en) 2000-02-23 2000-04-12 Astrazeneca Uk Ltd Novel use
GB0004151D0 (en) 2000-02-23 2000-04-12 Astrazeneca Uk Ltd Novel use
SE0102640D0 (sv) * 2001-07-31 2001-07-31 Astrazeneca Ab Novel compounds

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB765849A (en) * 1953-09-21 1957-01-16 Univ Leeds Improvements in or relating to new aminoalkyl phenyl ethers
US3077472A (en) * 1961-03-21 1963-02-12 Univ Kansas Res Foundation 3-[4-(aminoalkoxy)-phenyl]-4-(4-oxyphenyl)-alkanes and alkenes
US3105854A (en) * 1958-11-06 1963-10-01 Ciba Geigy Corp Meta-substituted phenoxyethylamines

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB765849A (en) * 1953-09-21 1957-01-16 Univ Leeds Improvements in or relating to new aminoalkyl phenyl ethers
US3105854A (en) * 1958-11-06 1963-10-01 Ciba Geigy Corp Meta-substituted phenoxyethylamines
US3077472A (en) * 1961-03-21 1963-02-12 Univ Kansas Res Foundation 3-[4-(aminoalkoxy)-phenyl]-4-(4-oxyphenyl)-alkanes and alkenes

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3515741A (en) * 1964-04-20 1970-06-02 Boehringer Sohn Ingelheim 1-cyanophenoxy-2-amino-alkanes
US3538228A (en) * 1966-06-03 1970-11-03 Ciba Ltd Pharmaceutical preparations comprising sulphur-containing amino-compounds for the treatment of depressive conditions and methods therefor
US4059621A (en) * 1972-07-21 1977-11-22 Science Union Et Cie, Societe Francaise De Recherche Medicale Substituted benzamido propanolamines
US4105796A (en) * 1975-06-02 1978-08-08 Boehringer Ingelheim Gmbh Pharmaceutical compositions containing racemic or optically active 1-(2,6-dimethyl-phenoxy)-2-methylamino-propane and method of use
US4218472A (en) * 1977-08-05 1980-08-19 Ab Kabi Geminally disubstituted indene derivatives
US4922021A (en) * 1981-03-04 1990-05-01 Basf Aktiensellschaft New alkylene diamine derivatives
US4795758A (en) * 1986-02-10 1989-01-03 Societe A Responsabilite Limitee: Institut De Recherches Chimiques Et Biologiques Appliquees (I.R.C.E.B.A.) 5-[2-(pyrrolidin-1-yl)ethoxy]-p-cymene derivatives, the process for the preparation of the said derivatives and drugs in which the said derivatives are present
WO1997015548A1 (en) * 1995-10-27 1997-05-01 Astra Aktiebolag New [(3-alkoxy-phenoxy)-ethyl]-dialkylamine derivatives and their use as local anaesthetics
US6310252B1 (en) 1995-10-27 2001-10-30 Astrazeneca Ab [(3-alkoxy-phenoxy)-ethyl]-dialkylamine derivatives and their use as local anaesthetics

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BE640617A (en:Method) 1964-05-29
FR3075M (fr) 1965-01-18
GB1014348A (en) 1965-12-22

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