US5494908A
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Substituted 3-(aminoalkylamino)-1,2-benzisoxazoles and related compounds
Assignee: Aventis Pharmaceuticals Inc
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Filing: 1993-11-12
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Granted: 1996-02-27
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Expires: 2013-11-12
Abstract
Abstract This application relates to compounds of the formula ##STR1## wherein R 1 , X, Y and n are as defined in the specification; and pharmaceutically acceptable addition salts thereof and optical and geometric isomers or racemic mixtures thereof; which compounds are useful for the treatment of various memory dysfunctions characterized by a decreased cholinergic function such as Alzheimer's disease. Compounds of this invention also inhibit monoamine oxidase and hence are useful as antidepressants.
Inventors
- 👤 Gerard J. O'Malley
- 👤 Mark G. Palermo
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 11:14
CPC Classifications
C; C07; C07D; C07D413/00; C07D413/02; C07D413/12; C07D261/00; C07D261/20; C07D413/14; C07D417/00; C07D417/02; C07D417/12
Claims Analysis
Total Claims: 33
Claim 1
Independent Claim
134 words
A compound of the formula ##STR230## wherein X is hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxymethyleneoxy, aryl(C 1 -C 6 )alkoxy, halo, hydroxy, (C 1 -C 6 )alkanoylamino, aminocarbonyloxy, (C 1 -C 10 )alkylaminocarbonyloxy, di(C 1 -C 10 )alkylaminocarbonyloxy, aryl(C 1 -C 10 )alkylaminocarbonyloxy, (C 1 -C 6 )alkoxycarbonyloxy, tetrahydroisoquinolylcarbonyloxy or aryl(C 1 -C 6 )alkylcarbonyloxy; R 1 is hydrogen, (C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxycarbonyl, aryloxycarbonyl, aryl(C 1 -C 6 )alkoxycarbonyl, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, or di(C 1 -C 6 )alkylaminocarbonyl; m is an integer from 2 to 7; n is an integer from 0 to 3; and pharmaceutically acceptable acid addition salts thereof and optical and geometric isomers or racemic mixtures thereof.
Claim 2
Dependent Claim
134 words
A compound of the formula ##STR230## wherein X is hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxymethyleneoxy, aryl(C 1 -C 6 )alkoxy, halo, hydroxy, (C 1 -C 6 )alkanoylamino, aminocarbonyloxy, (C 1 -C 10 )alkylaminocarbonyloxy, di(C 1 -C 10 )alkylaminocarbonyloxy, aryl(C 1 -C 10 )alkylaminocarbonyloxy, (C 1 -C 6 )alkoxycarbonyloxy, tetrahydroisoquinolylcarbonyloxy or aryl(C 1 -C 6 )alkylcarbonyloxy; R 1 is hydrogen, (C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxycarbonyl, aryloxycarbonyl, aryl(C 1 -C 6 )alkoxycarbonyl, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, or di(C 1 -C 6 )alkylaminocarbonyl; m is an integer from 2 to 7; n is an integer from 0 to 3; and pharmaceutically acceptable acid addition salts thereof and optical and geometric isomers or racemic mixtures thereof.
Claim 3
Dependent Claim
20 words
A pharmaceutically composition which comprises a pharmaceutically acceptable carrier and a pharmaceutically effective amount of the compound of claim 1.
Claim 4
Dependent Claim
20 words
A method of treating depression which comprises administering to a patient an effective amount of the compound of claim 1.
Claim 5
Dependent Claim
60 words
The compound of claim 1 wherein X is hydrogen, hydroxy, halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 8 )alkylaminocarbonyloxy, tetrahydroisoquinolylcarbonyloxy, di(C 1 -C 8 )alkylaminocarbonyloxy or aryl(C 1 -C 6 )alkylaminocarbonyloxy; R 1 is hydrogen or (C 1 -C 6 )alkyl; n is 1 or 2; and m is 2, 3 or 4.
Claim 6
Dependent Claim
42 words
The compound of claim 4 wherein X is hydrogen, 5-hydroxy, 5-methoxy, 5-methylaminocarbonyloxy, 5-dimethylaminocarbonyloxy, 5-methylethylaminocarbonyloxy, 5-bromo, 7-bromo, 5-phenylmethylaminocarbonyloxy, 6-chloro, 6-hydroxy, 6-methoxy, 6-methylaminocarbonyloxy, 6-methylethylaminocarbonyloxy, 6-dimethylaminocarbonyloxy, 6-phenylmethylaminocarbonyloxy, 5-hexylaminocarbonyloxy, 5-heptylaminocarbonyloxy, 5-tetrahydroisoquinol-2-ylcarbonyloxy, 6-hexylaminocarbonyloxy, 6-heptylaminocarbonyloxy or 6-tetrahydroisoquinol-2-ylcarbonyloxy; R 1 is hydrogen, methyl or methylaminocarbonyl; and m is 2.
Claim 7
Dependent Claim
15 words
The compound of claim 5 which is 6-methoxy-N-methyl-N-[2-(4-morpholinyl)ethyl]-1,2-benzisoxazol-3-amine and its pharmaceutically acceptable acid addition salts.
Claim 8
Dependent Claim
15 words
The compound of claim 5 which is 3-[[2-(4-morpholinyl)ethyl]methylamino]-1,2-benzisoxazol-6-ol and its pharmaceutically acceptable acid addition salts.
Claim 9
Dependent Claim
16 words
The compound of claim 5 which is 3-[[2-(4-morpholinyl)ethyl]methylamino]-1,2-benzisoxazol-6-yl methylcarbamate and its pharmaceutically acceptable acid addition salts.
Claim 10
Dependent Claim
18 words
The compound of claim 5 which is 3-[[2-(4-morpholin-yl)ethyl]methylamino]-1,2-benzisoxazo 1-6-yl phenylmethyl carbamate and its pharmaceutically acceptable addition acid salts.
Claim 11
Dependent Claim
17 words
The compound of claim 5 which is 3-[[2-(4-morpholinyl)ethyl]methylamino]-1,2-benzisoxazol-6-yl 1-methylethyl carbamate and its pharmaceutically acceptable acid addition salts.
Claim 12
Dependent Claim
15 words
The compound of claim 5 which is N-methyl-N-[2-(4-morpholinyl)ethyl]-1,2-benzisoxazol-3-amine and its pharmaceutically acceptable acid addition salts.
Claim 13
Dependent Claim
15 words
The compound of claim 5 which is N-[2-(4-morpholinyl)ethyl]1,2-benzisoxazol-3-amine and its pharmaceutically acceptable acid addition salts.
Claim 14
Dependent Claim
15 words
The compound of claim 5 which is 6-methoxy-N-[2-(4-morpholinyl)ethyl]-1,2-benzisoxazol-3-amine and its pharmaceutically acceptable acid addition salts.
Claim 15
Dependent Claim
15 words
The compound of claim 5 which is 3-[[2-(4-morpholinyl)ethyl]amino]-1,2-benzisoxazol-6-ol and its pharmaceutically acceptable acid addition salts.
Claim 16
Dependent Claim
15 words
The compound of claim 5 which is 3-[[2-(4-morpholinyl)ethyl]methylamino]-1,2-benzisoxazol-5-ol and its pharmaceutically acceptable acid addition salts.
Claim 17
Dependent Claim
17 words
The compound of claim 5 which is 3-[[2-(4-morpholinyl)ethyl]amino]-1,2-benzisoxazol-6-yl methyl carbamate and its pharmaceutically acceptable acid addition salts.
Claim 18
Dependent Claim
16 words
The compound of claim 5 which is 3-[[2-(4-morpholinyl)ethyl]amino]-1,2-benzisoxazol-5-yl methylcarbamate and its pharmaceutically acceptable acid addition salts.
Claim 19
Dependent Claim
15 words
The compound of claim 5 which is 6-chloro-N-[2-(4-morpholinyl)ethyl]-1,2-benzisoxazol-3-amine and its pharmaceutically acceptable acid addition salts.
Claim 20
Dependent Claim
15 words
The compound of claim 5 which is 5-methoxy-N-[2-(4-morpholinyl)ethyl]-1,2-benzisoxazole-3-amine and its pharmaceutically acceptable acid addition salts.
Claim 21
Dependent Claim
15 words
The compound of claim 5 which is 7-bromo-6-methoxy-N-methyl-N-[2-(4-morpholinyl)ethyl]-1,2-benzisoxazol-3-amine and its pharmaceutically acceptable acid addition salts.
Claim 22
Dependent Claim
16 words
The compound of claim 5 which is 3-[[2-(4-morpholinyl)ethyl]amino]-1,2-benzisoxazol-6-yl dimethylcarbamate and its pharmaceutically acceptable acid addition salts.
Claim 23
Dependent Claim
15 words
The compound of claim 5 which is 5-bromo-6-methoxy-N-[2-(4-morpholinyl)ethyl]-1,2-benzisoxazol-3-amine and its pharmaceutically acceptable acid addition salts.
Claim 24
Dependent Claim
16 words
The compound of claim 5 which is 3-[[(methylamino)carbonyl][2-(4-morpholinyl)ethyl]amino]-1,2-benzisoxazol-6-yl methylcarbamate and its pharmaceutically acceptable acid addition salts.
Claim 25
Dependent Claim
16 words
The compound of claim 5 which is 3-[[(methylamino)carbonyl][2-(4-morpholinyl)ethyl]amino]-1,2-benzisoxazol-5-yl methylcarbamate and its pharmaceutically acceptable acid addition salts.
Claim 26
Dependent Claim
16 words
The compound of claim 5 which is 7-bromo-3-N-methyl, N-2-(4-morpholinyl)ethyl]amino-1,2-benzisoxazol-6-ol and its pharmaceutically acceptable acid addition salts.
Claim 27
Dependent Claim
17 words
The compound of claim 5 which is 7-bromo-3-[N-methyl, N-2-(4-morpholinyl)ethyl]amino-1,2-benzisoxazol-6-yl dimethylcarbamate and its pharmaceutically acceptable acid addition salts.
Claim 28
Dependent Claim
134 words
A compound of the formula ##STR231## wherein X is hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxymethyleneoxy, aryl(C 1 -C 6 )alkoxy, halo, hydroxy, (C 1 -C 6 )alkanoylamino, aminocarbonyloxy, (C 1 -C 10 )alkylaminocarbonyloxy, di(C 1 -C 10 )alkylaminocarbonyloxy, aryl(C 1 --C 10 )alkylaminocarbonyloxy, (C 1 -C 6 )alkoxycarbonyloxy, tetrahydroisoquinolylcarbonyloxy or aryl(C 1 -C 6 )alkylcarbonyloxy; R 1 is hydrogen, (C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxycarbonyl, aryloxycarbonyl, aryl(C 1 -C 6 )alkoxycarbonyl, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, or di(C 1 -C 6 )alkylaminocarbonyl; m is an integer from 2 to 7; n is an integer from 0 to 3; and pharmaceutically acceptable acid addition salts thereof and optical and geometric isomers or racemic mixtures thereof.
Claim 29
Dependent Claim
134 words
A compound of the formula ##STR231## wherein X is hydrogen, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxymethyleneoxy, aryl(C 1 -C 6 )alkoxy, halo, hydroxy, (C 1 -C 6 )alkanoylamino, aminocarbonyloxy, (C 1 -C 10 )alkylaminocarbonyloxy, di(C 1 -C 10 )alkylaminocarbonyloxy, aryl(C 1 --C 10 )alkylaminocarbonyloxy, (C 1 -C 6 )alkoxycarbonyloxy, tetrahydroisoquinolylcarbonyloxy or aryl(C 1 -C 6 )alkylcarbonyloxy; R 1 is hydrogen, (C 1 -C 6 )alkyl, aryl(C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxycarbonyl, aryloxycarbonyl, aryl(C 1 -C 6 )alkoxycarbonyl, aminocarbonyl, (C 1 -C 6 )alkylaminocarbonyl, or di(C 1 -C 6 )alkylaminocarbonyl; m is an integer from 2 to 7; n is an integer from 0 to 3; and pharmaceutically acceptable acid addition salts thereof and optical and geometric isomers or racemic mixtures thereof.
Claim 30
Dependent Claim
65 words
The compound of claim 27 wherein X is hydrogen, hydroxy, halo, (C 1 -C 6 )alkyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkoxymethyleneoxy, (C 1 -C 8 )alkylaminocarbonyloxy, tetrahydroisoquinolylcarbonyloxy, di(C 1 -C 8 )alkylaminocarbonyloxy or aryl(C 1 -C 6 )alkylaminocarbonyloxy; R 1 is hydrogen or (C 1 -C 6 )alkyl; n is 1 or 2; and m is 2, 3 or 4.
Claim 31
Dependent Claim
42 words
The compound of claim 28 wherein X is hydrogen, 5-hydroxy, 5-methoxy, 5-methylaminocarbonyloxy, 5-dimethylaminocarbonyloxy, 5-methylethylaminocarbonyloxy, 5-bromo, 7-bromo, 6-methoxymethoxy, 5-phenylmethylaminocarbonyloxy, 6-chloro, 6-hydroxy, 6-methoxy, 6-methylaminocarbonyloxy, 6-methylethylaminocarbonyloxy, 6-dimethylaminocarbonyloxy, 6-phenylmethylaminocarbonyloxy, 5-hexylaminocarbonyloxy, 5-heptylaminocarbonyloxy, 5-tetrahydroisoquinol-2-ylcarbonyloxy, 6-hexylaminocarbonyloxy, 6-heptylaminocarbonyloxy or 6-tetrahydroisoquinol-2-ylcarbonyloxy; R 1 is hydrogen or methyl; and m is 2.
Claim 32
Dependent Claim
15 words
The compound of claim 29 which is 6-methoxymethoxy-N-[2-(4-thiomorpholinyl)ethyl]-1,2-benzisoxazol-3-amine and its pharmaceutically acceptable acid addition salts.
Claim 33
Dependent Claim
13 words
The compound of claim 29 which is 3-[[2-(4-thiomorpholinyl)ethyl]amine]-1,2-benzisoxazol-6-ol and pharmaceutically acceptable addition salts.
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 7.5 Years (Year 8) | 2003-02-26 | 2003-08-28 | 2004-02-27 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2007-02-26 | 2007-08-28 | 2008-02-27 | $7700.00 | Window Closed / Lapsed |