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US4460580A
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N-Alkylated aminoalcohols and their pharmaceutical compositions useful for the treatment of cardiac insufficiency
Assignee: Novartis Corp
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Filing: 1982-06-24
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Granted: 1984-07-17
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Expires: 2002-06-24
Abstract
Abstract The invention relates to novel N-alkylated aminoalcohols of the formula <IMAGE> (I) in which Ar is a radical of aromatic character which is unsubstituted or substituted by hydroxyl, n has the values nought or 1 and Alk is an alkylene radical having 2 to 5 carbon atoms and the nitrogen atom and the oxygen atom or, if n is nought, the salicylamide radical are separated from one another by at least two carbon atoms in the straight-chain, and their salts. The main action of the novel compounds consists in a stimulation of cardiac beta -receptors; the compounds also effect a blockage of adrenergic alpha -receptors and a lowering in the blood pressure. They can therefore be used as beta -stimulators, especially as agents having a positively inotropic action for the treatment of cardiac insufficiency. Compounds of the formula I in which Ar is phenyl, unsubstituted or substituted by 1 or 2 hydroxyl groups, Alk is an alkylene radical having 2 to 4 carbon atoms, n has the value 1, and the nitrogen atom and the oxygen atom are separated from one another by at least 2 carbon atoms in the straight-chain, or salts thereof, exhibit effects on the central nervous system, which are reflected for example in the suppression of the symptoms of impaired sympathetic functions and in the suppression of lack of initiative. Such compounds of the formula I therefore can be used for the treatment of reactive or endogenic states of depression of varying degrees of severity, and also for the treatment of neurotic or other psychic disturbances involving loss of initiative and depressive disorders. Such compounds can also be used for the short-term treatment of post-partum or postoperative depression, or of depression of different origin. Such compounds of the formula I can be used on their own or in combination with other antidepressants.
Inventors
- 👤 Franz Ostermayer
- 👤 Markus Zimmermann
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-09 06:28
CPC Classifications
C; C07; C07C; C07C231/00; C07C231/02; C07D; C07D265/00; C07D265/04; C07D265/12; C07D265/14; C07D265/20; C07D265/22; A; A61; A61P; A61P25/00; A61P25/02; A61P9/00; A61P9/04; C07C229/00; C07C229/38; C07D213/00; C07D213/02; C07D213/04; C07D213/24; C07D213/36; C07D213/38; C07D307/00; C07D307/02; C07D307/34; C07D307/38; C07D307/52; C07D333/00; C07D333/02; C07D333/04; C07D333/06; C07D333/14; C07D333/20
Claims Analysis
Total Claims: 42
Claim 1
Independent Claim
95 words
A compound of the formula ##STR25## in which Ar is phenyl or pyridyl unsubstituted or substituted by 1 or 2 hydroxyl groups, n has the values 0 or 1 and Alk is an alkylene radical having 2 to 5 carbon atoms, and the nitrogen atom and the oxygen atom appearing in the group ##STR26## or, if n is 0, the salicylamide radical, are separated from one another by at least 2 carbon atoms, in the form of racemates, a mixture of racemates, or an optical antipode, or a pharmaceutically acceptable non-toxic acid addition salt thereof.
Claim 2
Dependent Claim
95 words
A compound of the formula ##STR25## in which Ar is phenyl or pyridyl unsubstituted or substituted by 1 or 2 hydroxyl groups, n has the values 0 or 1 and Alk is an alkylene radical having 2 to 5 carbon atoms, and the nitrogen atom and the oxygen atom appearing in the group ##STR26## or, if n is 0, the salicylamide radical, are separated from one another by at least 2 carbon atoms, in the form of racemates, a mixture of racemates, or an optical antipode, or a pharmaceutically acceptable non-toxic acid addition salt thereof.
Claim 3
Dependent Claim
11 words
A compound as claimed in claim 1, which is alpha-[N-[2-(3-Carbamoyl-4-hydroxy-phenoxy)-1-methylethyl]-aminomethyl]-benzyl alcohol.
Claim 4
Dependent Claim
15 words
The enantiomer pair of the compound of claim 2 with a melting point of 166°-168°.
Claim 5
Dependent Claim
15 words
The enantiomer pair of the compound of claim 2 with a melting point of 152°-154°.
Claim 6
Dependent Claim
11 words
A compound as claimed in claim 1, which is alpha-[N-[2-(3-Carbamoyl-4-hydroxy-phenoxy)-1-methylethyl]-amino methyl]-3-pyridinemethanol.
Claim 7
Dependent Claim
10 words
A compound as claimed in claim 1, which is alpha-[N-[2-(3-Carbamoyl-4-hydroxy-phenoxy)-1-methylethyl]-aminoethyl-2-pyridinemethanol.
Claim 8
Dependent Claim
11 words
A compound as claimed in claim 1, which is alpha-[N-[2-(3-carbamoyl-4-hydroxy-phenoxy)-1,1-dimethyl-ethyl]-aminomethyl]-benzyl alcohol.
Claim 9
Dependent Claim
11 words
A compound as claimed in claim 1, which is alpha-[N-[4-(3-carbamoyl-4-hydroxy-phenoxy)-butyl]-aminomethyl]-benzyl alcohol.
Claim 10
Dependent Claim
11 words
A compound as claimed in claim 1, which is alpha-[N-[2-(4-Carbamoyl-3-hydroxy-phenoxy)-1-methylethyl]-aminomethyl]-benzyl alcohol.
Claim 11
Dependent Claim
15 words
The enantiomer pair of the compound of claim 9 with a melting point of 171°-173°.
Claim 12
Dependent Claim
15 words
The enantiomer pair of the compound of claim 9 with a melting point of 149°-151°.
Claim 13
Dependent Claim
11 words
A compound as claimed in claim 1 which is alpha-[N-[2-(3-Carbamoyl-4-hydroxy-phenoxy)-ethyl]-aminomethyl]-benzyl alcohol.
Claim 14
Dependent Claim
11 words
A compound as claimed in claim 1 which is alpha-[N-[2-(4-Carbamoyl-3-hydroxy-phenoxy)-ethyl]-aminomethyl]-benzyl alcohol.
Claim 15
Dependent Claim
9 words
The hydrochloride salt of the compound of claim 13.
Claim 16
Dependent Claim
10 words
The neutral fumarate salt of the compound of claim 5.
Claim 17
Dependent Claim
10 words
A compound as claimed in claim 1 which is alpha-[N-[2-(3-Carbamoyl-4-hydroxy-phenoxy)-1-methylethyl]-aminomethyl]-2-pyridinemethanol.
Claim 18
Dependent Claim
10 words
The neutral fumarate salt of the compound of claim 16.
Claim 19
Dependent Claim
11 words
A compound as claimed in claim 1 which is alpha-[N-[2-(3-Carbamoyl-4-hydroxy-phenoxy)-1-methylethyl]-aminomethyl]-4-hydroxybenzyl alcohol.
Claim 20
Dependent Claim
9 words
The fumarate salt of the compound of claim 18.
Claim 21
Dependent Claim
16 words
The enantiomer pair of the compound of claim 19 with a melting point of 209°-212° (decomposition).
Claim 22
Dependent Claim
11 words
A compound as claimed in claim 1 which is R-(-)-alpha-[N-[2-(3-Carbamoyl-4-hydroxy-phenoxy)-1-methylethyl]-aminomethyl]-benzyl alcohol.
Claim 23
Dependent Claim
9 words
The hydrochloride salt of the compound of claim 21.
Claim 24
Dependent Claim
14 words
The enantiomer of the compound of claim 22 with a melting point of 180°-184°.
Claim 25
Dependent Claim
11 words
A compound as claimed in claim 1 which is alpha-[N-[2-(3-Carbamoyl-4-hydroxy-phenoxy)-ethyl]-aminomethyl]-4-hydroxybenzyl alcohol.
Claim 26
Dependent Claim
11 words
A compound as claimed in claim 1 which is alpha-[N-[2-(2-Carbamoyl-3-hydroxy-phenoxy)-ethyl]-aminomethyl]benzyl alcohol.
Claim 27
Dependent Claim
9 words
The hydrochloride salt of the compound of claim 25.
Claim 28
Dependent Claim
11 words
A compound as claimed in claim 1 which is alpha-[N-[3-(4-Carbamoyl-3-hydroxy-phenoxy)-propyl]-aminomethyl]-benzyl alcohol.
Claim 29
Dependent Claim
10 words
A compound as claimed in claim 1 which is alpha-[N-[2-(3-Carbamoyl-4-hydroxy-phenoxy-ethyl]-aminomethyl]-2-pyridinemethanol.
Claim 30
Dependent Claim
11 words
A compound as claimed in claim 1 which is S-(+)-[N-[2-(3-Carbamoyl-4-hydroxy-phenoxy-1-methylethyl]-aminomethyl]-benzyl alcohol.
Claim 31
Dependent Claim
14 words
The enantiomer of the compound of claim 29 with a melting point of 160°-162°.
Claim 32
Dependent Claim
15 words
The enantiomer of the compound of claim 30 in the form of the hydrochloride salt.
Claim 33
Dependent Claim
11 words
A compound as claimed in claim 1 which is alpha-[N-[2-(4-Carbamoyl-3-hydroxy-phenoxy)-ethyl]-aminomethyl]-4-hydroxy-benzyl alcohol.
Claim 34
Dependent Claim
11 words
A compound as claimed in claim 1 which is alpha-[N-[3-(3-Carbamoyl-4-hydroxy-phenoxy)-propyl]-aminomethyl]-benzyl alcohol.
Claim 35
Dependent Claim
9 words
The hydrochloride salt of the compound of claim 33.
Claim 36
Dependent Claim
11 words
A compound as claimed in claim 1 which is alpha-[N-[3-(3-Carbamoyl-4-hydroxy-phenyl)-propyl]-aminomethyl]-benzyl alcohol.
Claim 37
Dependent Claim
11 words
A compound as claimed in claim 1 which is alpha-[N-[2-(3-Carbamoyl-4-hydroxy-phenoxy)-ethyl]-aminomethyl]-3,5-dihydroxybenzyl alcohol.
Claim 38
Dependent Claim
11 words
A compound as claimed in claim 1 which is (R)-(-)-alpha-[N-[2-(3-carbamoyl-4-hydroxy-phenoxy)-1,1-dimethyl-ethyl]-aminoethyl]-benzyl alcohol.
Claim 39
Dependent Claim
11 words
A compound as claimed in claim 1 which is (R)-(-)-alpha-[N-[2-(3-carbamoyl-4-hydroxy-phenoxy)-ethyl]-aminoethyl]-benzyl alcohol.
Claim 40
Dependent Claim
11 words
A compound as claimed in claim 1 which is (S)-(+)-alpha-[N-[2-(3-carbamoyl-4-hydroxy-phenoxy)-ethyl]-aminomethyl]-benzyl alcohol.
Claim 41
Dependent Claim
46 words
A pharmaceutical composition useful as a cardioselective β-stimulator for the treatment of cardiac insufficiency comprising a therapeutically effective amount of a compound of the formula I as claimed in claim 1 or a pharmaceutically acceptable non-toxic acid addition salt thereof together with a pharmaceutically usable carrier.
Claim 42
Dependent Claim
36 words
A method for the treatment of cardiac insufficiency in a warm-blooded animal which comprises administering a therapeutically effective amount of a compound of the formula I defined in claim 1 to an animal in need thereof.
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) | 1987-07-17 | 1988-01-16 | 1988-07-17 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-07-17 | 1992-01-16 | 1992-07-17 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-07-17 | 1996-01-16 | 1996-07-17 | $7700.00 | Window Closed / Lapsed |