US4835151A
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Pharmaceutical compositions and medical uses of dioxopiperidine derivatives
Assignee: BTG International Ltd
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Filing: 1987-12-23
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Granted: 1989-05-30
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Expires: 2007-12-23
Abstract
Abstract Phenyl-3-aminoalkyl-4-methyl-2,6-dioxopiperidines of the Formula I ##STR1## wherein: R 1 represents methoxy, ethoxy or hydroxy, R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3, and a pharmacologically acceptable acid addition salt thereof (a) have anxiolytic activity, (b) antagonize the anxiogenic activity of benzodiazepine inverse agonists, (c) reduce chronic abnormally high brain levels of serotonin or its metabolite 5-hydroxy-indoleacetic acid and (d) have antibacterial and antiviral activity. These activities are believed to be related to a reduction in serotonin turnover caused by blocking the depolarization activation of tryptophan hydroxylase. Novel compositions comprise the compounds with a benzodiazepine agonist or benzodiazepine inverse agonist.
Inventors
- 👤 Maurice W. Gittos
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-02 13:12
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/33; A61K31/395; A61K31/435; A61K31/44; A61K31/445; A61P; A61P25/00; A61P25/20; A61P25/30
Claims Analysis
Total Claims: 14
Claim 1
Independent Claim
98 words
A method of treating anxiety which comprises coadministering to a patient suffering anxiety, an effective anxiolytic amount of a compound of Formula I with a benzodiazepine agonist, the ratio of the compound of Formula I to benzodiazepine agonist being from 400:1 to 4:1, said Formula I being ##STR3## wherein: R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3; or a pharmaceutically acceptable acid addition salt thereof.
Claim 2
Independent Claim
98 words
A method of treating anxiety which comprises coadministering to a patient suffering anxiety, an effective anxiolytic amount of a compound of Formula I with a benzodiazepine agonist, the ratio of the compound of Formula I to benzodiazepine agonist being from 400:1 to 4:1, said Formula I being ##STR3## wherein: R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3; or a pharmaceutically acceptable acid addition salt thereof.
Claim 3
Dependent Claim
24 words
The method of claim 1 in which the benzodiazepine agonist is selected from chlorodiazepoxide, diazepam, bromazepam, prazepam, oxazepam, medazepam, lorazepam, chlorazepate, nitrazepam, and flunitrazepam.
Claim 4
Independent Claim
109 words
A method of treating anxiety which comprises coadministering to a patient suffering anxiety, an effective anxiolytic amount of a compound of Formula I with a benzodiazepine agonist, administered in a dosage of 50 to 700 mg per day, the ratio of the compound of Formula I to benzodiazepine agonist being from 400:1 to 4:1, said Formula I being ##STR4## wherein: R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3; or a pharmacologically acceptable acid addition salt thereof.
Claim 5
Independent Claim
109 words
A method of treating anxiety which comprises coadministering to a patient suffering anxiety, an effective anxiolytic amount of a compound of Formula I with a benzodiazepine agonist, administered in a dosage of 50 to 700 mg per day, the ratio of the compound of Formula I to benzodiazepine agonist being from 400:1 to 4:1, said Formula I being ##STR4## wherein: R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3; or a pharmacologically acceptable acid addition salt thereof.
Claim 6
Dependent Claim
121 words
A pharmaceutical composition comprising (a) a benzodiazepine agonist or benzodiazepine inverse agonist and (b) a compound of Formula I, said Formula I being ##STR5## wherein R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3; or a pharmacologically acceptable acid addition salt thereof; said benzodiazepine agonist being present in a ratio of the compound of Formula I to benzodiazepine agonist of from 400:1 to 4:1, and said benzodiazepine inverse agonist being present in a ratio of the compound of Formula I to benzodiazepine inverse agonist of from 200:1 to 4.1.
Claim 7
Dependent Claim
121 words
A pharmaceutical composition comprising (a) a benzodiazepine agonist or benzodiazepine inverse agonist and (b) a compound of Formula I, said Formula I being ##STR5## wherein R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3; or a pharmacologically acceptable acid addition salt thereof; said benzodiazepine agonist being present in a ratio of the compound of Formula I to benzodiazepine agonist of from 400:1 to 4:1, and said benzodiazepine inverse agonist being present in a ratio of the compound of Formula I to benzodiazepine inverse agonist of from 200:1 to 4.1.
Claim 8
Dependent Claim
22 words
The composition of claim 4, containing a benzodiazepine agonist selected from chlorodiazepoxide, diazepam, bromazepam, prazepam, oxazepam, medazepam, lorazepam, chlorazapate, nitrazepam, and flunitrazepam.
Claim 9
Dependent Claim
167 words
A pharmaceutical composition comprising (a) a benzodiazepine agonist or benzodiazepine inverse agonist and (b) a compound of Formula I, said Formula I being ##STR6## wherein: R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3, or a pharmacologically acceptable acid addition salt thereof, said compound of Formula I being administered in a dosage of 25 to 200 mg per unit dose, said benzodiazepine agonist being administered in a dosage of 0.05 to 50 mg per unit dose and being present in a ratio of the compound of Formula I to benzodizepine agonist of from 400:1 to 4:1, and said benzodiazepine inverse agonist being administered in a dosage of 0.05 to 50 mg per unit dose and being present in a ratio of the compound of Formula I to benzodiazepine inverse agonist of from 200:1 to 4:1.
Claim 10
Dependent Claim
167 words
A pharmaceutical composition comprising (a) a benzodiazepine agonist or benzodiazepine inverse agonist and (b) a compound of Formula I, said Formula I being ##STR6## wherein: R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3, or a pharmacologically acceptable acid addition salt thereof, said compound of Formula I being administered in a dosage of 25 to 200 mg per unit dose, said benzodiazepine agonist being administered in a dosage of 0.05 to 50 mg per unit dose and being present in a ratio of the compound of Formula I to benzodizepine agonist of from 400:1 to 4:1, and said benzodiazepine inverse agonist being administered in a dosage of 0.05 to 50 mg per unit dose and being present in a ratio of the compound of Formula I to benzodiazepine inverse agonist of from 200:1 to 4:1.
Claim 11
Dependent Claim
92 words
A pharmaceutical composition comprising (a) a benzodiazepine agonist and (b) a compound of Formula I, said Formula I being ##STR7## wherein: R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3; or a pharmacologically acceptable acid addition salt thereof, said benzodiazepine agonist being present in a ratio of the compound of Formula I to benzodiazepine agonist of from 400:1 to 4:1.
Claim 12
Dependent Claim
92 words
A pharmaceutical composition comprising (a) a benzodiazepine agonist and (b) a compound of Formula I, said Formula I being ##STR7## wherein: R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3; or a pharmacologically acceptable acid addition salt thereof, said benzodiazepine agonist being present in a ratio of the compound of Formula I to benzodiazepine agonist of from 400:1 to 4:1.
Claim 13
Dependent Claim
95 words
A pharmaceutical composition comprising (a) a benzodiazepine inverse agonist and (b) a compound of Formula I, said Formula I being ##STR8## wherein: R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3, or a pharmacologically acceptable acid addition salt thereof, said benzodiazepine inverse agonist being present in a ratio of the compound of Formula I to benzodiazepine inverse agonist of from 200:1 to 4:1.
Claim 14
Dependent Claim
95 words
A pharmaceutical composition comprising (a) a benzodiazepine inverse agonist and (b) a compound of Formula I, said Formula I being ##STR8## wherein: R 1 represents methoxy, ethoxy or hydroxy; R 2 represents methoxy, ethoxy, hydroxy or hydrogen; each R 3 independently represents methyl or ethyl; R 4 represents hydrogen or methyl; R 5 represents hydrogen or methyl; and n represents 2 or 3, or a pharmacologically acceptable acid addition salt thereof, said benzodiazepine inverse agonist being present in a ratio of the compound of Formula I to benzodiazepine inverse agonist of from 200:1 to 4:1.
References Cited (Backward Citations)
US3963729A
Cited
US4461771A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1992-05-29 | 1992-11-28 | 1993-05-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1996-05-29 | 1996-11-28 | 1997-05-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2000-05-29 | 2000-11-28 | 2001-05-30 | $7700.00 | Window Closed / Lapsed |