US4351842A
Expired / Lapsed
US
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N-Cyclopropylisoindolines
Assignee: Glaxo Laboratories Ltd
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Filing: 1980-07-21
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Granted: 1982-09-28
•
Expires: 2000-07-21
Abstract
Abstract Compounds of the general formula: ##STR1## in which A is a benzene ring or a carbocyclic aromatic group consisting of two or three fused benzene rings, the group A being linked to the nitrogen containing ring at two adjacent carbon atoms and the benzene ring or each benzene ring optionally carrying one or more substituents which may be the same or different, and may be alkyl, aryl, halo, hydroxy, acyloxy or alkoxy, or two adjacent positions in a ring may be substituted so as to form a methylene dioxy group (--O--CH 2 --O--); R 1 and R 2 which may be the same or different, each represent hydrogen; an alkyl group which contains 1 to 6 carbon atoms and which may be substituted; a hydroxycarbonyl or an alkoxycarbonyl group; and one of R 3 and R 4 represents hydrogen, an alkyl group which contains 1 to 6 carbon atoms and which may be substituted, or a hydroxy, alkoxy, hydroxycarbonyl or alkoxycarbonyl group and the other of R 3 and R 4 represents hydrogen, or a non-toxic physiologically acceptable salt or bioprecursor thereof. These compounds are useful in the treatment of patients suffering from depression.
Inventors
- 👤 Richard J. Coles
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 02:07
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/44; C07D209/48; A; A61; A61P; A61P25/00; A61P25/26; C07C; C07C51/00; C07C51/347; C07C51/367; C07C51/373; C07D209/56; C07D209/58; C07D209/60; C07D209/62; C07D491/00; C07D491/02; C07D491/04
Claims Analysis
Total Claims: 35
Claim 1
Independent Claim
272 words
A compound of the formula: ##STR11## in which A is a benzene ring or a carbocyclic aromatic group consisting of two benzene rings, the group A being linked to the nitrogen containing ring at two adjacent carbon atoms and the benzene ring or each benzene ring is unsubstituted or substituted by one or more substituents which may be the same or different, and are selected from the group consisting of alkyl containing 1-6 carbon atoms, phenyl, halogen, hydroxy, alkanoyloxy containing 1-6 carbon atoms in the alkanoyl portion or benzoyloxy, alkoxy containing 1-6 carbon atoms and a methylene dioxy group (O--CH 2 --O--) which is connected to two adjacent positions in a ring; R 1 and R 2 which may be the same or different, each represent hydrogen; an alkyl group which contains 1-6 carbon atoms and which is unsubstituted or substituted by hydroxy, alkanoyloxy containing 1-6 carbon atoms in the alkanoyl portion or benzoyloxy, alkoxy containing 1-6 carbon atoms, halogen, an alkylamino or dialkylamino group wherein the alkyl contains 1-6 carbon atoms; a hydroxycarbonyl or an alkoxycarbonyl group wherein the alkoxy contains 1-6 carbon atoms; and one of R 3 and R 4 represents hydrogen, an alkyl group which contains 1-6 carbon atoms, and which is unsubstituted or substituted by hydroxy, alkanoyloxy containing 1-6 carbon atoms in the alkanoyl portion or benzoyloxy, alkoxy containing 1-6 carbon atoms, halogen, an alkylamino or dialkylamino group wherein the alkyl contains 1-6 carbon atoms; hydroxy, alkoxy, hydroxycarbonyl or alkoxycarbonyl group wherein each alkoxy contains 1-6 carbon atoms and the other R 3 and R 4 represents hydrogen, or a non-toxic physiologically acceptable salt, or hydrate thereof.
Claim 2
Dependent Claim
272 words
A compound of the formula: ##STR11## in which A is a benzene ring or a carbocyclic aromatic group consisting of two benzene rings, the group A being linked to the nitrogen containing ring at two adjacent carbon atoms and the benzene ring or each benzene ring is unsubstituted or substituted by one or more substituents which may be the same or different, and are selected from the group consisting of alkyl containing 1-6 carbon atoms, phenyl, halogen, hydroxy, alkanoyloxy containing 1-6 carbon atoms in the alkanoyl portion or benzoyloxy, alkoxy containing 1-6 carbon atoms and a methylene dioxy group (O--CH 2 --O--) which is connected to two adjacent positions in a ring; R 1 and R 2 which may be the same or different, each represent hydrogen; an alkyl group which contains 1-6 carbon atoms and which is unsubstituted or substituted by hydroxy, alkanoyloxy containing 1-6 carbon atoms in the alkanoyl portion or benzoyloxy, alkoxy containing 1-6 carbon atoms, halogen, an alkylamino or dialkylamino group wherein the alkyl contains 1-6 carbon atoms; a hydroxycarbonyl or an alkoxycarbonyl group wherein the alkoxy contains 1-6 carbon atoms; and one of R 3 and R 4 represents hydrogen, an alkyl group which contains 1-6 carbon atoms, and which is unsubstituted or substituted by hydroxy, alkanoyloxy containing 1-6 carbon atoms in the alkanoyl portion or benzoyloxy, alkoxy containing 1-6 carbon atoms, halogen, an alkylamino or dialkylamino group wherein the alkyl contains 1-6 carbon atoms; hydroxy, alkoxy, hydroxycarbonyl or alkoxycarbonyl group wherein each alkoxy contains 1-6 carbon atoms and the other R 3 and R 4 represents hydrogen, or a non-toxic physiologically acceptable salt, or hydrate thereof.
Claim 3
Dependent Claim
13 words
The compound as defined in claim 1 wherein A is a benzene ring.
Claim 4
Dependent Claim
19 words
The compound as defined in claim 1 wherein A is a carbocyclic aromatic group consisting of two benzene rings.
Claim 5
Dependent Claim
16 words
The compound as defined in claim 3 wherein the two benzene rings form a benz[e] isoindoline.
Claim 6
Dependent Claim
21 words
The compound as defined in claim 3 wherein R 1 and R 2 are hydrogen and the benzene rings are unsubstituted.
Claim 7
Dependent Claim
16 words
The compound as defined in claim 3 wherein the two benzene rings form a benz[f] isoindoline.
Claim 8
Dependent Claim
32 words
A compound as claimed in claim 1 in which any of the groups R 1 to R 4 or a substituent on A is an alkyl group which contains 1-4 carbon atoms.
Claim 9
Dependent Claim
32 words
A compound as claimed in claim 1 in which any of the groups R 3 or R 4 or a substituent on A is an alkoxy group which contains 1-6 carbon atoms.
Claim 10
Dependent Claim
28 words
A compound as claimed in claim 1 in which a substituent on A is an alkanoyloxy group which contains 1-6 carbon atoms in the alkanoyl portion or benzoyloxy.
Claim 11
Dependent Claim
43 words
A compound as claimed in claim 1 in which any of the groups R 1 to R 4 is an alkyl group which is substituted by hydroxy, alkanoyloxy containing 1-6 carbon atoms in the alkanoyl portion or benzoyloxy; alkoxy, halo, alkylamino or dialkylamino.
Claim 12
Dependent Claim
19 words
A compound as claimed in claim 1 in which any of the substituents on A is a phenyl group.
Claim 13
Dependent Claim
14 words
A compound as claimed in claim 1 in which A is benzene, or naphthalene.
Claim 14
Dependent Claim
62 words
A compound as claimed in claim 1 in which R 1 is hydrogen, alkyl, hydroxyalkyl, alkoxycarbonyl or dialkylaminoalkyl; R 2 is hydrogen, alkyl or hydroxyalkyl, one of the groups R 3 and R 4 is hydrogen, alkyl, alkoxy, hydroxyalkyl or alkoxyalkyl, and the other is hydrogen, and the substituents on A other than hydrogen, are halogen, alkyl, phenyl, alkoxy, hydroxy or methylenedioxy.
Claim 15
Dependent Claim
75 words
A compound as claimed in claim 1 in which R 1 and R 2 are both hydrogen, or one is alkyl and the other hydrogen; R 3 and R 4 are both hydrogen or R 3 is alkyl, hydroxyalkyl, alkoxyalkyl, alkanoyloxy containing 1-6 carbon atoms in the alkanoyl portion or benzoyloxy, and R 4 is hydrogen and A contains no substituents other than hydrogen, or contains one such substituent which is hydroxy, alkoxy or halo.
Claim 16
Dependent Claim
30 words
The compound as claimed in claim 14 wherein R 3 is alkyl, hydroxyalkyl, alkoxyalkyl, alkanoyloxy containing 1-6 carbon atoms in the alkanoyl portion or benzoyloxy and R 4 is hydrogen.
Claim 17
Dependent Claim
10 words
A compound as claimed in claim 1 which is 2-cyclopropyl-isoindoline.
Claim 18
Dependent Claim
12 words
A compound as claimed in claim 1 which is 2-cyclopropyl benz[e] isoindoline.
Claim 19
Dependent Claim
12 words
A compound as claimed in claim 1 which is 2-cyclopropyl benz[f] isoindoline.
Claim 20
Dependent Claim
15 words
A compound as claimed in claim 1 which is 2-(1'-hydroxymethylcyclopropyl) benz[e] isoindoline or its hydrochloride.
Claim 21
Dependent Claim
10 words
A compound as claimed in claim 1 which is 2-cyclopropyl-5-hydroxyisoindoline.
Claim 22
Dependent Claim
10 words
A compound as claimed in claim 1 which is 2-cyclopropyl-6-methoxy-2,3-dihydro-1H-naphth[2',3-d]-azol-2-ine.
Claim 23
Dependent Claim
12 words
A compound as claimed in claim 1 which is 2-(1'-methoxymethylcyclopropyl) benz[f] isoindoline.
Claim 24
Dependent Claim
11 words
A compound as claimed in claim 1 which is 2-cyclopropyl-1-ethylbenz[f] isoindoline.
Claim 25
Dependent Claim
10 words
A compound as claimed in claim 1 which is 2-(1'-methylcyclopropyl)-6-fluoro-2,3-dihydro-1H-naphth[2',3'-d]azol-1-ine
Claim 26
Dependent Claim
10 words
A compound as claimed in claim 1 which is 2-cyclopropylisoindoline.
Claim 27
Dependent Claim
10 words
A compound as claimed in claim 1 which is 6-chloro-2-cyclopropyl-2,3-dihydro-1H-naphth[2',3'-d]azol-2-ine.
Claim 28
Dependent Claim
10 words
A compound as claimed in claim 1 which is 6-fluoro-2-cyclopropyl-2,3-dihydro-1H-naphth[2',3'-d]azol-2-ine.
Claim 29
Dependent Claim
11 words
A compound as claimed in claim 1 which is 2-(1'-methylcyclopropyl)benz[f] isoindoline.
Claim 30
Dependent Claim
10 words
A compound as claimed in claim 1 which is 2-cyclopropyl-4-fluoro-isoindoline.
Claim 31
Dependent Claim
31 words
A pharmaceutical preparation containing as active ingredient an effective amount of a compound as claimed in claim 1 having anti-depressant activity in admixture with a pharmaceutically acceptable non-tox carrier of diluent.
Claim 32
Dependent Claim
12 words
A pharmaceutical preparation as claimed in claim 30 in unit dosage form.
Claim 33
Dependent Claim
18 words
A pharmaceutical preparation as claimed in claim 31 which contains from 5 to 100 mg of active ingredient.
Claim 34
Dependent Claim
25 words
A pharmaceutical preparation as claimed in claim 30 which is in the form of tablets or capsules, or as granules formulated with a sweetening agent.
Claim 35
Dependent Claim
27 words
A method of treatment of a patient suffering from depression which comprises administering to the patient an effective amount of a compound as claimed in claim 1.
References Cited (Backward Citations)
DD31901A
Cited
US2740795A
Cited
BE827087A
Cited
US3996373A
Cited
US3897452A
Cited
US4052508A
Cited
US4088772A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1985-09-27 | 1986-03-29 | 1986-09-28 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1989-09-27 | 1990-03-29 | 1990-09-28 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1993-09-27 | 1994-03-29 | 1994-09-28 | $7700.00 | Window Closed / Lapsed |