US4421767A
Expired / Lapsed
US
⏱️ 0.0 years remaining
Compounds and methods for treating depression
Assignee: Merrell Toraude et Cie
•
Filing: 1982-09-13
•
Granted: 1983-12-20
•
Expires: 2002-09-13
Abstract
Abstract Compounds of the formula: ##STR1## wherein: X is fluorine, chlorine, or bromine; R is the group R 2 as defined below; R 1 is a group of the formula: ##STR2## or the group R 2 as defined below; wherein R 2 is: ##STR3## wherein R 3 is hydrogen, (C 1 -C 4 )alkyl, or (C 1 -C 4 )alkoxy, and R 4 is (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy; or a (C 1 -C 8 )alkyl ester thereof; or a non-toxic pharmaceutically acceptable salt thereof, inhibit MAO in vivo and can be administered either alone or in combination with an aromatic L-amino acid decarboxylase inhibitor for the treatment of depression.
Inventors
- 👤 Michael G. Palfreyman
- 👤 Ian A. McDonald
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-29 09:24
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/02; C07D309/08; C07D309/10; C07D309/12; A; A61; A61K; A61K31/00; A61K31/185; A61K31/19; A61K31/195; C07C; C07C45/00; C07C45/61; C07C45/63; C07C45/67; C07C45/673
Claims Analysis
Total Claims: 37
Claim 1
Independent Claim
91 words
A compound of the formula: ##STR25## wherein: X is fluorine, chlorine, or bromine; R is the group R 2 as defined below; R 1 is a group of the formula: ##STR26## or the group R 2 as defined below; wherein R 2 is: ##STR27## wherein R 3 is hydrogen, (C 1 -C 4 )alkyl, or (C 1 -C 4 )alkoxy, and R 4 is (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy; or a (C 1 -C 8 )alkyl ester thereof; or a non-toxic pharmaceutically acceptable salt thereof.
Claim 2
Dependent Claim
91 words
A compound of the formula: ##STR25## wherein: X is fluorine, chlorine, or bromine; R is the group R 2 as defined below; R 1 is a group of the formula: ##STR26## or the group R 2 as defined below; wherein R 2 is: ##STR27## wherein R 3 is hydrogen, (C 1 -C 4 )alkyl, or (C 1 -C 4 )alkoxy, and R 4 is (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy; or a (C 1 -C 8 )alkyl ester thereof; or a non-toxic pharmaceutically acceptable salt thereof.
Claim 3
Dependent Claim
10 words
A compound of Formula I as defined in claim 1.
Claim 4
Dependent Claim
10 words
A compound of Formula II as defined in claim 1.
Claim 5
Dependent Claim
10 words
A compound of Formula III as defined in claim 1.
Claim 6
Dependent Claim
14 words
A compound as defined in claim 2, 3, or 4 wherein X is fluorine.
Claim 7
Dependent Claim
14 words
A compound as defined in claim 3 or 4 wherein R 1 is: ##STR28##
Claim 8
Dependent Claim
11 words
A compound as defined in claim 6 wherein X is fluorine.
Claim 9
Dependent Claim
18 words
A compound as defined in claim 7 which is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid or a non-toxic pharmaceutically acceptable salt thereof.
Claim 10
Dependent Claim
26 words
A compound as defined in claim 7 which is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid, (C 1 -C 8 )alkyl ester or a non-toxic pharmaceutically acceptable acid addition salt thereof.
Claim 11
Dependent Claim
22 words
A compound as defined in claim 9 which is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid, methyl ester or a non-toxic pharmaceutically acceptable acid addition salt thereof.
Claim 12
Dependent Claim
22 words
A compound as defined in claim 9 which is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid, ethyl ester or a non-toxic pharmaceutically acceptable acid addition salt thereof.
Claim 13
Dependent Claim
48 words
A compound as defined in claim 2, 3, or 4 wherein R or R 1 is: ##STR29## wherein R 3 is hydrogen, (C 1 -C 4 )alkyl, or (C 1 -C 4 )-alkoxy, and R 4 is (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy.
Claim 14
Dependent Claim
12 words
A compound as defined in claim 12 wherein R 3 is hydrogen.
Claim 15
Dependent Claim
11 words
A compound as defined in claim 12 wherein X is fluorine.
Claim 16
Dependent Claim
11 words
A compound as defined in claim 13 wherein X is fluorine.
Claim 17
Dependent Claim
20 words
A pharmaceutical composition comprising (a) a compound as defined in claim 1, and (b) a pharmaceutically acceptable carrier or diluent.
Claim 18
Dependent Claim
24 words
A pharmaceutical composition as defined in claim 16 in unit dosage form containing 10 μg to 100 mg of said compound per unit dose.
Claim 19
Dependent Claim
28 words
A pharmaceutical composition comprising (a) a compound as defined in claim 1, (b) an aromatic L-amino acid decarboxylase (AADC) inhibitor, and (c) a pharmaceutically acceptable carrier or diluent.
Claim 20
Dependent Claim
23 words
A pharmaceutical composition as defined in claim 18 wherein the AADC inhibitor is carbidopa, benzerazide, or a 2-amino-2-(monofluoromethyl or difluoromethyl)-3-(monohydroxyphenyl or dihydroxyphenyl)propionic acid.
Claim 21
Dependent Claim
13 words
A composition as defined in claim 19 wherein the AADC inhibitor is carbidopa.
Claim 22
Dependent Claim
25 words
A composition as defined in claim 16, 17, 18, 19, or 20 wherein said compound is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid or a non-toxic pharmaceutically acceptable salt thereof.
Claim 23
Dependent Claim
33 words
A composition as defined in claim 16, 17, 18, 19, or 20 wherein said compound is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid, (C 1 -C 8 )alkyl ester or a non-toxic pharmaceutically acceptable acid addition salt thereof.
Claim 24
Dependent Claim
24 words
A composition as defined in claim 22 wherein said compound is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid, methyl ester or a non-toxic pharmaceutically acceptable acid addition salt thereof.
Claim 25
Dependent Claim
24 words
A composition as defined in claim 22 wherein said compound is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid, ethyl ester or a non-toxic pharmaceutically acceptable acid addition salt thereof.
Claim 26
Dependent Claim
46 words
A composition as defined in claim 16, 17, 18, 19, or 20 wherein said compound is a compound of Formula II as defined in claim 1, wherein R 1 is: ##STR30## wherein R 4 is (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy.
Claim 27
Dependent Claim
11 words
A composition as defined in claim 25 wherein X is fluorine.
Claim 28
Dependent Claim
23 words
A method for treating depression which comprises administering to a depressed patient an effective amount of a compound as defined in claim 1.
Claim 29
Dependent Claim
67 words
A method for treating depression which comprises administering to a depressed patient on effective amount of a compound as defined in claim 1 in combination with an effective amount of an aromatic L-amino acid decarboxylase (AADC) inhibitor, the amount of inhibitor being sufficient to substantially block the AADC catalyzed decarboxylation of said compound extracerebrally without substantially blocking the AADC catalyzed decarboxylation of said compound in the brain.
Claim 30
Dependent Claim
22 words
A method as defined in claim 28 wherein the AADC inhibitor is carbidopa, benzerazide, or a 2-amino-2-(monofluoromethyl or difluoromethyl)-3-(monohydroxyphenyl or dihydroxyphenyl)propionic acid.
Claim 31
Dependent Claim
13 words
A method as defined in claim 29 wherein the AADC inhibitor is carbidopa.
Claim 32
Dependent Claim
25 words
A method as defined in claim 27, 28, 29, or 30 wherein said compound administered is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid or a non-toxic pharmaceutically acceptable salt thereof.
Claim 33
Dependent Claim
33 words
A method as defined in claim 27, 28, 29, or 30 wherein said compound administered is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid, (C 1 -C 8 )alkyl ester or a non-toxic pharmaceutically acceptable acid addition salt thereof.
Claim 34
Dependent Claim
25 words
A method as defined in claim 32 wherein said compound administered is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid, methyl ester or a non-toxic pharmaceutically acceptable acid addition salt thereof.
Claim 35
Dependent Claim
25 words
A method as defined in claim 32 wherein said compound administered is 2-amino-4-fluoro-3-(3'-hydroxyphenyl)-3-butenoic acid, ethyl ester or a non-toxic pharmaceutically acceptable acid addition salt thereof.
Claim 36
Dependent Claim
46 words
A method as defined in claim 27, 28, 29, or 30 wherein said compound administered is a compound of Formula II as defined in claim 1 wherein R 1 is: ##STR31## wherein R 4 is (C 1 -C 4 )alkyl or (C 1 -C 4 )alkoxy.
Claim 37
Dependent Claim
11 words
A method as defined in claim 35 wherein X is fluorine.
References Cited (Backward Citations)
US3023235A
Cited
US3046300A
Cited
GB998355A
Cited
US3329711A
Cited
US3553258A
Cited
US3725470A
Cited
EP0000034A1
Cited
FR2392958A1
Cited
EP0007600A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1986-12-19 | 1987-06-20 | 1987-12-20 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1990-12-19 | 1991-06-20 | 1991-12-20 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1994-12-19 | 1995-06-20 | 1995-12-20 | $7700.00 | Window Closed / Lapsed |