US4034106A
Expired / Lapsed
US
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Alkanolamine derivatives
Assignee: Imperial Chemical Industries Ltd
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Filing: 1975-06-02
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Granted: 1977-07-05
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Expires: 1995-06-02
Abstract
Abstract Novel 1-heterocyclyloxy- or 1-aryloxy-3-amido-alkylamino-2-propanol derivatives, processes for their manufacture, pharmaceutical compositions containing them and methods of using them in the treatment of heart diseases. The compounds possess beta -adrenergic blocking activity. Representative of the compounds disclosed is 1-(4-indolyloxy)-3- beta -isobutyramidoethylamino-2-propanol.
Inventors
- 👤 Leslie Harold Smith
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-27 10:10
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/04; C07D209/08; C07D209/10; C07D209/18; C07D209/30; C07D209/42; C07D213/00; C07D213/02; C07D213/04; C07D213/60; C07D213/78; C07D213/81; C07D215/00; C07D215/02; C07D215/16; C07D215/20; C07D215/22; C07D215/233; C07D215/48; C07D231/00; C07D231/02; C07D231/10; C07D231/14; C07D231/38; C07D231/40; C07D235/00; C07D235/02; C07D235/04; C07D235/06; C07D235/16; C07D239/00; C07D239/02; C07D239/24; C07D239/28; C07D239/32; C07D239/34; C07D277/00; C07D277/02; C07D277/20; C07D277/22; C07D277/30; C07D277/32; C07D277/34; C07D307/00; C07D307/02; C07D307/34; C07D307/56; C07D307/68; C07D307/77; C07D307/78; C07D307/79; C07D307/82; C07D307/84; C07D311/00; C07D311/02; C07D311/04; C07D311/22; C07D319/00; C07D319/10; C07D319/14; C07D319/16; C07D319/18; C07D333/00; C07D333/02; C07D333/04; C07D333/06; C07D333/24; C07D333/26; C07D333/38; C07D333/50; C07D333/52; C07D333/54; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/55
Claims Analysis
Total Claims: 12
Claim 1
Independent Claim
289 words
An alkanolamine derivative selected from a compound of the formula: R.OCH.sub.2.CHOH.CH.sub.2 NH--A--NH--X--Y--R.sup.1 wherein A is alkylene of from 2 to 12 carbon atoms; wherein X is carbonyl (--CO--); wherein Y is a direct link, or is alkylene or alkyleneoxy each of up to 6 carbon atoms, and wherein R is aryl of the formula: ##STR15## and R 1 is aryl of the formula: ##STR16## wherein R 2 , R 3 , R 12 and R 13 , which may be the same or different, each is hydrogen, halogen, hydroxy, amino, nitro or cyano, or alkyl, hydroxyalkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkylthio, cycloalkoxy, alkenyloxy, alkynyloxy or alkanoyl each of up to 6 carbon atoms or aryl, aryloxy or dialkylamino each of up to 12 carbon atoms; or wherein R 2 and R 3 together, and/or R 12 and R 13 together, form trimethylene, tetramethylene, 1-oxotetramethylene, propenylene, but-2-enylene or buta-1,3-dienylene such that together with two adjacent carbon atoms of the benzene ring they form respectively indanyl, 5,6,7,8-tetrahydronaphthyl, 5-oxo-5,6,7,8-tetrahydronaphthyl, indenyl, 5,8-dihydronaphthyl or naphthyl; wherein R 4 is hydrogen or amidic of the formula: R.sup.15 R.sup.16 N--CO--Q-- r.sup.15 r.sup.16 n--co--nh--q-- r.sup.15 r.sup.16 n--co--q.sup.1 --o-- or R.sup.16 --X--NR.sup.15 --Q-- wherein Q is a direct link or is alkylene or alkenylene each of up to 6 carbon atoms; wherein Q 1 is alkylene of up to 6 carbon atoms; wherein R 15 is hydrogen or alkyl of up to 6 carbon atoms; wherein R 16 is hydrogen or alkenyl, cycloalkyl, hydroxyalkyl or alkoxyalkyl each of up to 6 carbon atoms, or alkyl, aryl, aralkyl, or aralkenyl each of up to 10 carbon atoms; wherein X is carbonyl; and wherein R 14 is amidic as defined above for R 4 ; and an acid-addition salt thereof.
Claim 2
Dependent Claim
289 words
An alkanolamine derivative selected from a compound of the formula: R.OCH.sub.2.CHOH.CH.sub.2 NH--A--NH--X--Y--R.sup.1 wherein A is alkylene of from 2 to 12 carbon atoms; wherein X is carbonyl (--CO--); wherein Y is a direct link, or is alkylene or alkyleneoxy each of up to 6 carbon atoms, and wherein R is aryl of the formula: ##STR15## and R 1 is aryl of the formula: ##STR16## wherein R 2 , R 3 , R 12 and R 13 , which may be the same or different, each is hydrogen, halogen, hydroxy, amino, nitro or cyano, or alkyl, hydroxyalkyl, cycloalkyl, alkenyl, alkynyl, alkoxy, alkylthio, cycloalkoxy, alkenyloxy, alkynyloxy or alkanoyl each of up to 6 carbon atoms or aryl, aryloxy or dialkylamino each of up to 12 carbon atoms; or wherein R 2 and R 3 together, and/or R 12 and R 13 together, form trimethylene, tetramethylene, 1-oxotetramethylene, propenylene, but-2-enylene or buta-1,3-dienylene such that together with two adjacent carbon atoms of the benzene ring they form respectively indanyl, 5,6,7,8-tetrahydronaphthyl, 5-oxo-5,6,7,8-tetrahydronaphthyl, indenyl, 5,8-dihydronaphthyl or naphthyl; wherein R 4 is hydrogen or amidic of the formula: R.sup.15 R.sup.16 N--CO--Q-- r.sup.15 r.sup.16 n--co--nh--q-- r.sup.15 r.sup.16 n--co--q.sup.1 --o-- or R.sup.16 --X--NR.sup.15 --Q-- wherein Q is a direct link or is alkylene or alkenylene each of up to 6 carbon atoms; wherein Q 1 is alkylene of up to 6 carbon atoms; wherein R 15 is hydrogen or alkyl of up to 6 carbon atoms; wherein R 16 is hydrogen or alkenyl, cycloalkyl, hydroxyalkyl or alkoxyalkyl each of up to 6 carbon atoms, or alkyl, aryl, aralkyl, or aralkenyl each of up to 10 carbon atoms; wherein X is carbonyl; and wherein R 14 is amidic as defined above for R 4 ; and an acid-addition salt thereof.
Claim 3
Dependent Claim
166 words
An alkanolamine derivative as claimed in claim 1 selected from a compound of the formula given in claim 1 wherein A is ethylene, 1-methylethylene or 1,1-dimethylethylene, wherein Y is a direct link or is methylene or methyleneoxy, and wherein R is aryl of the formula: ##STR17## and R 1 is aryl of the formula: ##STR18## wherein R 2 , R 3 , R 12 and R 13 , which may be the same or different, each is hydrogen, fluorine, chlorine, bromine, iodine, hydroxy, amino, nitro, cyano, methyl, ethyl, n-propyl, hydroxymethyl, 1-hydroxyethyl, cyclopropyl, cyclopentyl, allyl, ethynyl, methoxy, isopropoxy, methylthio, cyclopentyloxy, allyloxy, propargyloxy, formyl, acetyl, phenyl, phenoxy or dimethylamino, or wherein R 2 and R 3 together, and/or R 12 and R 13 together, are trimethylene, tetramethylene, 1-oxotetramethylene, propenylene, but-2-enylene or buta-1,3-dienylene; wherein R 4 is hydrogen, acetamido, propionamido, carbamoyl, carbamoylmethyl, acetamidomethyl, 3-methylureido, carbamoylmethoxy, 3-n-butylureido, N-methylcarbamoylmethoxy or N-β-hydroxyethylcarbamoylmethoxy and wherein R 14 is, other than hydrogen, as defined above for R 4 ; and an acid-addition salt thereof.
Claim 4
Dependent Claim
139 words
An alkanolamine derivative as claimed in claim 1 selected from a compound of the formula given in claim 1 wherein A is ethylene, 1-methylethylene or 1,1-dimethylethylene, wherein R and R 1 are both aryl, wherein R 2 is hydrogen, chloro, cyano, nitro or methoxy which is in the 2-position of the aryl nucleus, wherein R 3 , R 4 , R 12 and R 13 are all hydrogen, wherein R 14 has the formula: R.sup.16 NHCO--Q-- r.sup.16 nhconh-- r.sup.16 nhco--q.sup.1 --o-- or R.sup.16 --X--NH--Q-- wherein R 16 is hydrogen or methyl, wherein Q is a direct link or is methylene and wherein Q 1 is methylene, which substituent R 14 is in the 4-position of the aryl nucleus, wherein X is carbonyl and wherein Y is a direct link or is methylene or methyleneoxy, and an acid-addition salt thereof.
Claim 5
Dependent Claim
20 words
A compound selected from 1-phenoxy-3-β -(p-acetamidobenzamido)ethylamino-2-propanol; 1-(2-nitrophenoxy)-3-β -(p-acetamidophenylacetamido)ethylamino-2-propanol; 1-(2-methoxyphenoxy-3-β-(p-acetamidophenylacetamido)ethylamino-2-propanol; 1-(2-chlorophenoxy)-3-β -(p-acetamidophenylacetamido)ethylamino-2-propanol; 1-(2-cyanophenoxy)-3-β -(p-acetamidomethylphenoxyacetamido)ethylamino-2-propanol; 1-(2-cyanophenoxy)-3-β -(p-carbamoylmethoxyphenylacetamido)ethylamino-2-propanol; and an acid-additioon salt thereof.
Claim 6
Dependent Claim
20 words
A compound selected from 1-phenoxy-3-β -(p-acetamidobenzamido)ethylamino-2-propanol; 1-(2-nitrophenoxy)-3-β -(p-acetamidophenylacetamido)ethylamino-2-propanol; 1-(2-methoxyphenoxy-3-β-(p-acetamidophenylacetamido)ethylamino-2-propanol; 1-(2-chlorophenoxy)-3-β -(p-acetamidophenylacetamido)ethylamino-2-propanol; 1-(2-cyanophenoxy)-3-β -(p-acetamidomethylphenoxyacetamido)ethylamino-2-propanol; 1-(2-cyanophenoxy)-3-β -(p-carbamoylmethoxyphenylacetamido)ethylamino-2-propanol; and an acid-additioon salt thereof.
Claim 7
Dependent Claim
35 words
An acid-addition salt as claimed in claim 1 which is a hydrochloride, hydrobromide, phosphate, sulphate, oxalate, lactate, tartarate, acetate, salicylate, citrate, benzoate, β-naphthoate, adipate or 1,1-methylene-bis-(2-hydroxy-3-naphthoate), or a salt derived from a sulphonated polystyrene resin.
Claim 8
Dependent Claim
20 words
An alkanolamine derivative as claimed in claim 1 selected from the group consisting of 1-(2-cyanophenoxy)-3-β-(p-carbamoylmethoxyphenylacetamido)ethylamino-2-propanol; and an acid-addition salt thereof.
Claim 9
Dependent Claim
30 words
A pharmaceutical composition comprising as active ingredient at least one alkanolamine derivative or an acid-addition salt thereof, claimed in claim 1, in association with a pharmaceutically-acceptable diluent or carrier therefor.
Claim 10
Dependent Claim
49 words
A composition as claimed in claim 7 which contains, in addition to the alkanolamine derivative, one or more drugs selected from sedatives, vasodilators, diuretics, hypotensive agents, cardiac membrane stabilising agents, agents used in the treatment of Parkinson's disease and other tremors, cardiotonic agents, α-adrenergic blocking agents and sympathomimetic bronchodilators.
Claim 11
Dependent Claim
34 words
A method for the treatment of prophylaxis of heart diseases and hypertension in a warm-blooded animal which comprises administering to said animal an effective amount of at least one compound claimed in claim 1.
Claim 12
Dependent Claim
34 words
A method for producing coronary β-adrenergic blockade in a warm-blooded animal in need of such blockade which comprises administering to said animal an effective amount of at least one compound claimed in claim 1.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-07-04 | 1981-01-03 | 1981-07-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-07-04 | 1985-01-03 | 1985-07-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-07-04 | 1989-01-03 | 1989-07-05 | $7700.00 | Window Closed / Lapsed |