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Compounds and methods for treating depression

Assignee: Merrell Toraude et Cie

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Filing: 1982-09-13

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Granted: 1983-12-20

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Expires: 2002-09-13

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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 20:20

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

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

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