CA2010638A1 - Bisphenethanolamines - Google Patents
BisphenethanolaminesInfo
- Publication number
- CA2010638A1 CA2010638A1 CA002010638A CA2010638A CA2010638A1 CA 2010638 A1 CA2010638 A1 CA 2010638A1 CA 002010638 A CA002010638 A CA 002010638A CA 2010638 A CA2010638 A CA 2010638A CA 2010638 A1 CA2010638 A1 CA 2010638A1
- Authority
- CA
- Canada
- Prior art keywords
- ethyl
- hydroxy
- compounds
- chlorophenethyl
- amino
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/02—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
-
- 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
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K20/00—Accessory food factors for animal feeding-stuffs
- A23K20/10—Organic substances
- A23K20/111—Aromatic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Obesity (AREA)
- Pharmacology & Pharmacy (AREA)
- Hematology (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Polymers & Plastics (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Zoology (AREA)
- Animal Husbandry (AREA)
- Food Science & Technology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Fodder In General (AREA)
Abstract
Abstract 4-[2-[Bis[(R)-.beta.-hydroxy-3-chlorophenethyl]amino]ethyl]-phenoxyethanol and physiologically compatible salts thereof have catabolic activity and can be used for the treatment of obesity. of diabetes and of conditions which are associated with high protein breakdown, or as feed additives for fattening animals. They are manufactured starting from the phenol corresponding to the above--mentioned ester.
Description
Z010638 ~
The present invention i~ concerned with novel bi~phenethanoiamines, a proce66 for their manufacture and pharmaceutical prepacations ba6ed on these compounds, ag well as with the use of these compound6 in the control or prevention of illnes6e6.
The above bisphenethanolamines are 4-[2-rbisr~R)-~--hydroxy-3-chlorophenethyl]amino]ethyl]phenoxyethanol (hereinafter referred to as BAP) and phy6iologically compatible salts thereof. Example6 of such salts are salts of BAP with mineral acids such as hydrochloric acid, hydcobromic acid, sulphuric acid or pho~phoric acid or with organic acids such a~ oxalic acid, methanesulphonic aeid, acetic acid, propionic acid, citric acid, maleic acid, succinic acid, ~alic acid, fumaric acid, phenylacetic acid or ~alicylic acid. BAP maleate i8 preferred.
;~ The phenol ether BAP and it6 salts can be manufactured by etherifying the corresponding phenol, 4-[2-tbisr(R)-A- ~ ~ --hydroxy-3-chlorophenethyl]amino]ethyl]phenol, with an agent which introduces the 2-hydroxyethyl group and, if desired, converting the BAP obtained into a salt.
Exameles of agents which introduce the 2-hydroxyethyl group are 2-hydroxyethyl halides such as the chloride o~
bromide and 2-hydroxyethyl 6ulphonate6 6uch a6 ?-hydroxy-ethyl methane6ulphonate. The reaction of such an agent ~ ;
with the aboYe-mentioned phenol starting material can be carried out in a manner known per se, e.g. in a 601vent such as dimethyl 6ulphoxide (DMS0), acetone, tetrahydro-furan (THF) or n-propanol, in the eresence of a base ~uch M~/14.12.89 . ' ' ~ ~:
Z0~0638 as potassium hydroxide, potassium carbonate, potas6ium t-butylate or triethylamine, optionally under argon at a temperature up to the ceflux temperatuce of ehe reaction mixture, preferably at about 120~C.
The phenol starting material can be p~epared as described in Example lB) by reacting tyramine with (R)-m-chlorostyrene oxide in a solvent such aæ DMS0, acetonitrile, THF, dioxan or ethanol at a temperature betweer. 60C and the boiling point of the solvent.
BAP and its salts can be used as active ingredient~ in pharmaceutical preparations for the treatment of obesity and/or of diabetes mellitus, e~pecially of obese adult diabetics. In an animal experiment an increased cataboli~m, primarily of fat, has been observed upon the ~~~ administration of the said compounds. Furthermore, it has been ob6erved that these compounds stimulate the formation of brown adipose tissue in rats and obese-hyperglycaemic mice. It is known that defects of the brown adipose tissue play a sub~tantial role in the origin of obe6ity. In obese-hyperglycaemic mice and in ~treptozotocin-diabetic rats the above compounds have a pronounced antidiabetic effect, in that they have hypoglycaemic activity and reduce glycosuria. These compounds exhibit only a slight activity on the working of the heart and circulation. The dosage can amount to 0.5-1000 mg, preferably 2-600 mg, per day for an adult deeending on the individual requirements of the patient, whereby the dosage can be administered as a 6ingle dosage or in seYeral dosages divided over the day.
: :
In addition, in an animal experiment with BAP and its salts an increase in the body protein content and a decrease in the body fat content could be detected. The said compounds therefore lead to an increase in the lean composition of the body at the expense of fat.
- 3 _ 2 0 1 0 6 3 Accordingly, they can also be used in human medicine for the treatment of conditions which are associated with high protein breakdown. e.g in convale6cence after operation~.
In this case the do6ages administered are the same as in the treatment of obesity and/or of diabete6 mellitus.
BAP and its salts can also be u6ed in the maintenance of fattening animals such as beef cattle, pigs, sheep and poultry. In this case the dosages admini6tered and the dosage forms admini~tered can be the same as in the case of vitamins. The caid compounds can al~o be ufied as feed additives in dosages of 0.01-100 mg/kg depending on the substance, kind of animal and age.
The pharmaceutical preparations contain the active ingredient together with a compatible pharmaceutical organic or inorganic carrier material such as e.g. water, gelatine, gum arabic, lactose, starch, magnesium stearate, talc, vegeeable oils, polyalkylene glycols, Vaseline and the like. The pharmaceutical preparations are preferably administered orally, e.g. in the form of tablets, capsules, pill8. powders, granulates, 601ution~, syrups, suspensions, elixirs and the like. The administration can, however, also be effected parenterally, e.g. in the form of 6terile solutions, suspensions or emul6ions. The pharmaceutical preparations can be 6terilized and/or can contain ingredients such as prefierving agents, stabilizers, wetting agents, emul6ifiers, salts for varying the osmotic pressure and buffer substance~
The activity of BAP i8 evident from the following test results:
Activitv on oxY~en consumPtion Groups of 6 male albino rats weighing 160-180 g were placed in metabolic cage6 after fasting for Z4 hours. The cages were ventilated with a constant 6 litre room air/minute which was equilibrated at a dew point o ll~C.
Sample6 of the spent air were collected during periods of in each case 14 minutes after again eguilibrating and the oxygen content and C02 content were analyzed. After an adaptation time of 4 hours the animals received either placebo t5% gum arabic) or the test substance. namely BAP.
(suspended in 5% gum arabic) per 08 or intraperitoneally.
Thereafter, the detecminationg were carried out for a period of 12 hours. In the following Table there iB ~iven the average oxygen consumption after medication during the first 3 hours and the entire test duration (12 hours) a~ a per~entage of the oxygen consumption of the adaptation period, corresponding corrections for variation6 in the placebo group having been taken into con6ideration.
Table Dosage Oxygen con~umption (~M/kg) (% of the value of the pre-period) 1st to 3rd hour 1st to 12th hour 10 p.os` 191 157 3 p.os 179 137 1 p.os 156 122 0.3 p.o~ 105 10 i.p. 186 154 3 i.p. 174 134 1 i.p. 172 lZl 0.3 i.p.134 108 The following Examples illustrate the invention in more detail.
Example 1 ~;
~ -, -A) 186 mg of potassium hydroxide and 650 mg of 2-bromo-ethanol are added to a solution of 520 mg of 4-[Z--[bisr(R)-B-hydroxy-3-chlorophenethyl]amino]ethyl]phenol in 7 ml of n-propanol and the mixture i8 heated to lZ0C
for Z hour~. For the wocking-up, the mixture is poured on to ice-water and extracted with ethyl acetate. After washing with water, drying over NazSQ4 and evaporation of the solvent the extract gives 600 mg of crude oil.
After chromatography on 40 g of silica gel with chloro-form/n-propanol/aqueous ammonia (1000:10:1) there are obtained Z90 mg of BAP, ~a]D = -66 (c = 1.0 in methanol); ~Z25 = 14080.
B) For the prepara~ion of the phenol 6tarting material.
10.0 g of tyramine and 8.8 g of (R)-m-chlorostyrene oxide are heated to 100C in 300 ml of DMS0 for Z4 hours. A
further 17.5 g of (R)-m-chlorostyrene oxide are then added and the mixture i~ heated to 100C for a further 24 hours.
The solvent is then removed by evaporation in a high vacuum and the residue i8 chromatographed on 1 kg of silica gel with chloroform/n-propanol/saturated ammonia (1000:5:0.Z). The uniform fractions are combined. There are obtained 13 g of the desired phenol, r~]D =
22 (c = 0.8 in methanol).
~xam~le 2 Tablets of the following compo~ition are manufactured in the usual manner:
BAP 250 mg Lactose 200 mg Maize starch 300 mg Maize starch paste 50 mg Calcium stearate 5 mg Dicalcium phosphate 45 mg ~.
The present invention i~ concerned with novel bi~phenethanoiamines, a proce66 for their manufacture and pharmaceutical prepacations ba6ed on these compounds, ag well as with the use of these compound6 in the control or prevention of illnes6e6.
The above bisphenethanolamines are 4-[2-rbisr~R)-~--hydroxy-3-chlorophenethyl]amino]ethyl]phenoxyethanol (hereinafter referred to as BAP) and phy6iologically compatible salts thereof. Example6 of such salts are salts of BAP with mineral acids such as hydrochloric acid, hydcobromic acid, sulphuric acid or pho~phoric acid or with organic acids such a~ oxalic acid, methanesulphonic aeid, acetic acid, propionic acid, citric acid, maleic acid, succinic acid, ~alic acid, fumaric acid, phenylacetic acid or ~alicylic acid. BAP maleate i8 preferred.
;~ The phenol ether BAP and it6 salts can be manufactured by etherifying the corresponding phenol, 4-[2-tbisr(R)-A- ~ ~ --hydroxy-3-chlorophenethyl]amino]ethyl]phenol, with an agent which introduces the 2-hydroxyethyl group and, if desired, converting the BAP obtained into a salt.
Exameles of agents which introduce the 2-hydroxyethyl group are 2-hydroxyethyl halides such as the chloride o~
bromide and 2-hydroxyethyl 6ulphonate6 6uch a6 ?-hydroxy-ethyl methane6ulphonate. The reaction of such an agent ~ ;
with the aboYe-mentioned phenol starting material can be carried out in a manner known per se, e.g. in a 601vent such as dimethyl 6ulphoxide (DMS0), acetone, tetrahydro-furan (THF) or n-propanol, in the eresence of a base ~uch M~/14.12.89 . ' ' ~ ~:
Z0~0638 as potassium hydroxide, potassium carbonate, potas6ium t-butylate or triethylamine, optionally under argon at a temperature up to the ceflux temperatuce of ehe reaction mixture, preferably at about 120~C.
The phenol starting material can be p~epared as described in Example lB) by reacting tyramine with (R)-m-chlorostyrene oxide in a solvent such aæ DMS0, acetonitrile, THF, dioxan or ethanol at a temperature betweer. 60C and the boiling point of the solvent.
BAP and its salts can be used as active ingredient~ in pharmaceutical preparations for the treatment of obesity and/or of diabetes mellitus, e~pecially of obese adult diabetics. In an animal experiment an increased cataboli~m, primarily of fat, has been observed upon the ~~~ administration of the said compounds. Furthermore, it has been ob6erved that these compounds stimulate the formation of brown adipose tissue in rats and obese-hyperglycaemic mice. It is known that defects of the brown adipose tissue play a sub~tantial role in the origin of obe6ity. In obese-hyperglycaemic mice and in ~treptozotocin-diabetic rats the above compounds have a pronounced antidiabetic effect, in that they have hypoglycaemic activity and reduce glycosuria. These compounds exhibit only a slight activity on the working of the heart and circulation. The dosage can amount to 0.5-1000 mg, preferably 2-600 mg, per day for an adult deeending on the individual requirements of the patient, whereby the dosage can be administered as a 6ingle dosage or in seYeral dosages divided over the day.
: :
In addition, in an animal experiment with BAP and its salts an increase in the body protein content and a decrease in the body fat content could be detected. The said compounds therefore lead to an increase in the lean composition of the body at the expense of fat.
- 3 _ 2 0 1 0 6 3 Accordingly, they can also be used in human medicine for the treatment of conditions which are associated with high protein breakdown. e.g in convale6cence after operation~.
In this case the do6ages administered are the same as in the treatment of obesity and/or of diabete6 mellitus.
BAP and its salts can also be u6ed in the maintenance of fattening animals such as beef cattle, pigs, sheep and poultry. In this case the dosages admini6tered and the dosage forms admini~tered can be the same as in the case of vitamins. The caid compounds can al~o be ufied as feed additives in dosages of 0.01-100 mg/kg depending on the substance, kind of animal and age.
The pharmaceutical preparations contain the active ingredient together with a compatible pharmaceutical organic or inorganic carrier material such as e.g. water, gelatine, gum arabic, lactose, starch, magnesium stearate, talc, vegeeable oils, polyalkylene glycols, Vaseline and the like. The pharmaceutical preparations are preferably administered orally, e.g. in the form of tablets, capsules, pill8. powders, granulates, 601ution~, syrups, suspensions, elixirs and the like. The administration can, however, also be effected parenterally, e.g. in the form of 6terile solutions, suspensions or emul6ions. The pharmaceutical preparations can be 6terilized and/or can contain ingredients such as prefierving agents, stabilizers, wetting agents, emul6ifiers, salts for varying the osmotic pressure and buffer substance~
The activity of BAP i8 evident from the following test results:
Activitv on oxY~en consumPtion Groups of 6 male albino rats weighing 160-180 g were placed in metabolic cage6 after fasting for Z4 hours. The cages were ventilated with a constant 6 litre room air/minute which was equilibrated at a dew point o ll~C.
Sample6 of the spent air were collected during periods of in each case 14 minutes after again eguilibrating and the oxygen content and C02 content were analyzed. After an adaptation time of 4 hours the animals received either placebo t5% gum arabic) or the test substance. namely BAP.
(suspended in 5% gum arabic) per 08 or intraperitoneally.
Thereafter, the detecminationg were carried out for a period of 12 hours. In the following Table there iB ~iven the average oxygen consumption after medication during the first 3 hours and the entire test duration (12 hours) a~ a per~entage of the oxygen consumption of the adaptation period, corresponding corrections for variation6 in the placebo group having been taken into con6ideration.
Table Dosage Oxygen con~umption (~M/kg) (% of the value of the pre-period) 1st to 3rd hour 1st to 12th hour 10 p.os` 191 157 3 p.os 179 137 1 p.os 156 122 0.3 p.o~ 105 10 i.p. 186 154 3 i.p. 174 134 1 i.p. 172 lZl 0.3 i.p.134 108 The following Examples illustrate the invention in more detail.
Example 1 ~;
~ -, -A) 186 mg of potassium hydroxide and 650 mg of 2-bromo-ethanol are added to a solution of 520 mg of 4-[Z--[bisr(R)-B-hydroxy-3-chlorophenethyl]amino]ethyl]phenol in 7 ml of n-propanol and the mixture i8 heated to lZ0C
for Z hour~. For the wocking-up, the mixture is poured on to ice-water and extracted with ethyl acetate. After washing with water, drying over NazSQ4 and evaporation of the solvent the extract gives 600 mg of crude oil.
After chromatography on 40 g of silica gel with chloro-form/n-propanol/aqueous ammonia (1000:10:1) there are obtained Z90 mg of BAP, ~a]D = -66 (c = 1.0 in methanol); ~Z25 = 14080.
B) For the prepara~ion of the phenol 6tarting material.
10.0 g of tyramine and 8.8 g of (R)-m-chlorostyrene oxide are heated to 100C in 300 ml of DMS0 for Z4 hours. A
further 17.5 g of (R)-m-chlorostyrene oxide are then added and the mixture i~ heated to 100C for a further 24 hours.
The solvent is then removed by evaporation in a high vacuum and the residue i8 chromatographed on 1 kg of silica gel with chloroform/n-propanol/saturated ammonia (1000:5:0.Z). The uniform fractions are combined. There are obtained 13 g of the desired phenol, r~]D =
22 (c = 0.8 in methanol).
~xam~le 2 Tablets of the following compo~ition are manufactured in the usual manner:
BAP 250 mg Lactose 200 mg Maize starch 300 mg Maize starch paste 50 mg Calcium stearate 5 mg Dicalcium phosphate 45 mg ~.
Claims (8)
1. 4-[2-[Bis[(R)-.beta.-hydroxy-3-chlorophenethyl]amino]-ethyl]phenoxyethanol and physiologically compatible salts thereof.
2. Compounds according to claim 1 as therapeutically active substances, especially for the treatment of obesity, of diabetes mellitus and of conditions which are associated with high protein breakdown.
3. Pharmaceutical preparations containing a compound according to claim 1, especially for the treatment of obesity, of diabetes mellitus and of conditions which are associated with high protein breakdown.
4. Feedstuffs for fattening animals containing a compound according to claim 1.
5. A process for the manufacture of the compounds according to claim 1, which process comprises etherifying the phenol, 4-[2-[bis[(R)-.beta.-hydroxy-3-chlorophenethyl]-amino]ethyl]phenol, corresponding to 4-[2-[bis[(R)-.beta.--hydroxy-3-chlorophenethyl]amino]ethyl]phenoxyethanol with an agent which introduces the 2-hydroxyethyl group and, if desired, converting the compound obtained into a salt.
6. The use of a compound according to claim 1 for the manufacture of pharmaceutical preparations for the treatment of obesity, of diabetes mellitus and of conditions which are associated with high protein breakdown.
7. The compounds of claim 1, whenever prepared by the process of claim 5 or by an obvious chemical equivalent thereof.
8. The compounds, process, preparations and use as hereinbefore described, particularly with reference to the Examples.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH84189 | 1989-03-07 | ||
| CH841/89 | 1989-03-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2010638A1 true CA2010638A1 (en) | 1990-09-07 |
Family
ID=4196454
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002010638A Abandoned CA2010638A1 (en) | 1989-03-07 | 1990-02-22 | Bisphenethanolamines |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP0386603A3 (en) |
| JP (1) | JPH02279659A (en) |
| KR (1) | KR900014308A (en) |
| AU (1) | AU5061490A (en) |
| CA (1) | CA2010638A1 (en) |
| FI (1) | FI901145A0 (en) |
| HU (1) | HUT58039A (en) |
| IL (1) | IL93589A0 (en) |
| MC (1) | MC2104A1 (en) |
| NO (1) | NO901058L (en) |
| PT (1) | PT93348A (en) |
| ZA (1) | ZA901550B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9124512D0 (en) * | 1991-11-19 | 1992-01-08 | Smithkline Beecham Plc | Novel compounds |
| US5578638A (en) * | 1993-11-05 | 1996-11-26 | American Cyanamid Company | Treatment of glaucoma and ocular hypertension with β3 -adrenergic agonists |
| US5563171A (en) * | 1993-11-05 | 1996-10-08 | American Cyanamid Company | Treatment of glaucoma and ocular hypertension with β3-adrenergic agonists |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3169094D1 (en) * | 1980-11-20 | 1985-03-28 | Beecham Group Plc | Secondary amines |
| EP0118489A1 (en) * | 1982-08-27 | 1984-09-19 | Beecham Group Plc | Secondary arylethanolamines |
| AU592557B2 (en) * | 1985-04-16 | 1990-01-18 | F. Hoffmann-La Roche Ag | Phenethanolamine derivatives |
-
1990
- 1990-02-22 CA CA002010638A patent/CA2010638A1/en not_active Abandoned
- 1990-02-28 ZA ZA901550A patent/ZA901550B/en unknown
- 1990-02-28 EP EP19900103863 patent/EP0386603A3/en not_active Withdrawn
- 1990-03-01 IL IL93589A patent/IL93589A0/en unknown
- 1990-03-02 HU HU901260A patent/HUT58039A/en unknown
- 1990-03-02 JP JP2049658A patent/JPH02279659A/en active Pending
- 1990-03-02 MC MC902114A patent/MC2104A1/en unknown
- 1990-03-02 AU AU50614/90A patent/AU5061490A/en not_active Abandoned
- 1990-03-05 KR KR1019900002803A patent/KR900014308A/en not_active Application Discontinuation
- 1990-03-06 PT PT93348A patent/PT93348A/en not_active Application Discontinuation
- 1990-03-06 NO NO90901058A patent/NO901058L/en unknown
- 1990-03-07 FI FI901145A patent/FI901145A0/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP0386603A3 (en) | 1991-04-24 |
| JPH02279659A (en) | 1990-11-15 |
| PT93348A (en) | 1990-11-07 |
| NO901058D0 (en) | 1990-03-06 |
| HU901260D0 (en) | 1990-05-28 |
| MC2104A1 (en) | 1991-03-11 |
| AU5061490A (en) | 1990-09-13 |
| HUT58039A (en) | 1992-01-28 |
| NO901058L (en) | 1990-09-10 |
| ZA901550B (en) | 1990-11-28 |
| IL93589A0 (en) | 1990-12-23 |
| FI901145A0 (en) | 1990-03-07 |
| EP0386603A2 (en) | 1990-09-12 |
| KR900014308A (en) | 1990-10-23 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |