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US4003913A
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Pyrano- and thiopyranoindole derivatives, compositions and methods of use
Assignee: Wyeth Canada Inc
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Filing: 1975-03-05
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Granted: 1977-01-18
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Expires: 1995-03-05
Abstract
Abstract Pyranoindole and thiopyranoindole derivatives characterized by having an amino(lower)alkyl radical attached to either or both the 1 and 9 position of a pyrano[3,4-b]indole or thiopyrano[3,4-b]indole nucleus or having said radical attached to the 1 position of a pyrano[4,3-b]indole or thiopyrano[4,3-b]indole nucleus are disclosed. The amino portion of the amino(lower)alkyl radical may be further substituted with one or two lower alkyl groups or incorporated into a heterocyclic amine radical. The derivatives having the amino(lower)alkyl radical only at position 1 are further substituted at position 1 and may be optionally substituted at positions 3,4,5,6,7,8, and 9. The pyrano[3,4-b]indole or thiopyrano[3,4-b]indole derivatives having the amino(lower)alkyl radical only at position 9 possess two substituents at position 1 and may be optionally substituted at position 3,4,5,6,7, and 8; the derivatives having an amino(lower)alkyl radical at both positions 1 and 9 are further substituted at position 1 and may be optionally substituted at positions 3,4,5,6,7 and 8. The pyrano-and thiopyranoindole derivatives of this invention are useful antidepressant and antiulcer agents. Methods for the preparation and use of these derivatives are also disclosed.
Inventors
- 👤 Christopher A. Demerson
- 👤 Lesie G. Humber
- 👤 Andre A. Asselin
- 👤 Ivo Jirkovsky
- 👤 Thomas A. Dobson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 13:30
CPC Classifications
C; C07; C07D; C07D209/00; C07D209/02; C07D209/04; C07D209/08
Claims Analysis
Total Claims: 31
Claim 1
Independent Claim
386 words
A compound selected from those of the formulae 1 and 1a ##STR104##in which R 1 is lower alkyl or lower cycloalkyl; R 2 , R 3 , R 4 and R 5 are the same or different selected from the group consisting of hydrogen and lower alkyl; R 6 is hydrogen, lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, nitro or halo; R 7 is hydrogen, lower alkyl, lower alkenyl, propargyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of formula --Alk-NR 8 R 9 wherein Alk is an alkylene selected from the group consisting of CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl, and R 8 and R 9 are either the same or different selected from the group consisting of hydrogen and lower alkyl, or R 8 is lower alkyl and R 9 is p-chlorophenacyl, or R 8 and R 9 together with the nitrogen atom to which they are joined form a heterocyclic amine radical selected from the group consisting of 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl, 4-(lower alkyl)-1-piperazinyl and 4-[hydroxy(lower)alkyl]-1-piperazinyl; X is thio; and Y is lower alkyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of fromula --Alk--NR 8 R 9 wherein Alk is an alkylene selected from the group consisting of CR 10 R 11 , CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl and R 8 and R 9 are as defined herein; with the proviso that at least one of R 7 and Y is --Alk-NR 8 R 9 and that in the compounds of formula 1a, Y is -Alk NR 8 R 9 as defined herein; or a corresponding acid addition salt thereof with a pharmaceutically acceptable acid.
Claim 2
Dependent Claim
386 words
A compound selected from those of the formulae 1 and 1a ##STR104##in which R 1 is lower alkyl or lower cycloalkyl; R 2 , R 3 , R 4 and R 5 are the same or different selected from the group consisting of hydrogen and lower alkyl; R 6 is hydrogen, lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, nitro or halo; R 7 is hydrogen, lower alkyl, lower alkenyl, propargyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of formula --Alk-NR 8 R 9 wherein Alk is an alkylene selected from the group consisting of CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl, and R 8 and R 9 are either the same or different selected from the group consisting of hydrogen and lower alkyl, or R 8 is lower alkyl and R 9 is p-chlorophenacyl, or R 8 and R 9 together with the nitrogen atom to which they are joined form a heterocyclic amine radical selected from the group consisting of 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl, 4-(lower alkyl)-1-piperazinyl and 4-[hydroxy(lower)alkyl]-1-piperazinyl; X is thio; and Y is lower alkyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of fromula --Alk--NR 8 R 9 wherein Alk is an alkylene selected from the group consisting of CR 10 R 11 , CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl and R 8 and R 9 are as defined herein; with the proviso that at least one of R 7 and Y is --Alk-NR 8 R 9 and that in the compounds of formula 1a, Y is -Alk NR 8 R 9 as defined herein; or a corresponding acid addition salt thereof with a pharmaceutically acceptable acid.
Claim 3
Dependent Claim
6 words
1-[2-(Dimethylamino)ethyl]-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, as claimed in claim 1.
Claim 4
Dependent Claim
6 words
1-[2-(Dimethylamino)ethyl]-9-ethyl-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, as claimed in claim 1.
Claim 5
Dependent Claim
6 words
1,9-Dimethyl-1-[2-(dimethylamino)ethyl]-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, as claimed in claim 1.
Claim 6
Dependent Claim
6 words
1-[2-(Dimethylamino)ethyl]-1-methyl-9-propyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, as claimed in claim 1.
Claim 7
Dependent Claim
6 words
9-Ethyl-1-methyl-1-[2-(methylamino)ethyl]-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, as claimed in claim 1.
Claim 8
Dependent Claim
6 words
9-Ethyl-1-methyl-1-(2-aminoethyl)-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, as claimed in claim 1.
Claim 9
Dependent Claim
6 words
5-Ethyl-1-methyl-1-[2-(dimethylamino)ethyl]-1,2,3,4-tetrahydrothiopyrano[3,4-b]indole, as claimed in claim 1.
Claim 10
Dependent Claim
8 words
(+)- or (-)-1-[2-(Dimethylamino)ethyl]-9-ethyl-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, as claimed in claim 3.
Claim 11
Dependent Claim
6 words
9-Allyl-1-[2-(dimethylamino)ethyl]-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, as claimed in claim 1.
Claim 12
Independent Claim
14 words
A method of relieving the symptoms of depression in warm blooded animals which comprises:
Claim 13
Independent Claim
14 words
A method of relieving the symptoms of depression in warm blooded animals which comprises:
Claim 14
Dependent Claim
408 words
administering to said mammal an effective dose of from about 0.1 milligram to about 50 milligrams per kilogram of mammal weight per day of a compound selected from those of the formulae 1 and 1a ##STR105##in which R 1 is lower alkyl or lower cycloalkyl; R 2 , R 3 , R 4 and R 5 are the same or different selected from the group consisting of hydrogen and lower alkyl; R 6 is hydrogen, lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, nitro or halo; R 7 is hydrogen, lower alkyl, lower alkenyl, propargyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of formula -Alk-NR 8 R 9 wherein Alk is an alkylene selected from the group consisting of CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 , and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl and R 8 and R 9 are either the same or different selected from the group consisting of hydrogen and lower alkyl, or R 8 is lower alkyl and R 9 is p-chlorophenacyl, or R 8 and R 9 together with the nitrogen atom to which they are joined form a heterocyclic amine radical selected from the group consisting of 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl, 4-(lower alkyl)-1-piperazinyl and 4-[hydroxy(lower)alkyl]-1-piperazinyl; X is thio; and Y is lower alkyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of formula --Alk--NR 8 R 9 is an alkylene selected from the group consisting of CR 10 R 11 , CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl and R 8 and R 9 are as defined herein; with the proviso that at least one of R 7 and Y is --Alk--NR 8 R 9 and that in the compounds of formula 1a, Y is --Alk NR 8 R 9 as defined herein; and the corresponding acid addition salt with a pharmaceutically acceptable acid.
Claim 15
Dependent Claim
408 words
administering to said mammal an effective dose of from about 0.1 milligram to about 50 milligrams per kilogram of mammal weight per day of a compound selected from those of the formulae 1 and 1a ##STR105##in which R 1 is lower alkyl or lower cycloalkyl; R 2 , R 3 , R 4 and R 5 are the same or different selected from the group consisting of hydrogen and lower alkyl; R 6 is hydrogen, lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, nitro or halo; R 7 is hydrogen, lower alkyl, lower alkenyl, propargyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of formula -Alk-NR 8 R 9 wherein Alk is an alkylene selected from the group consisting of CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 , and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl and R 8 and R 9 are either the same or different selected from the group consisting of hydrogen and lower alkyl, or R 8 is lower alkyl and R 9 is p-chlorophenacyl, or R 8 and R 9 together with the nitrogen atom to which they are joined form a heterocyclic amine radical selected from the group consisting of 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl, 4-(lower alkyl)-1-piperazinyl and 4-[hydroxy(lower)alkyl]-1-piperazinyl; X is thio; and Y is lower alkyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of formula --Alk--NR 8 R 9 is an alkylene selected from the group consisting of CR 10 R 11 , CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl and R 8 and R 9 are as defined herein; with the proviso that at least one of R 7 and Y is --Alk--NR 8 R 9 and that in the compounds of formula 1a, Y is --Alk NR 8 R 9 as defined herein; and the corresponding acid addition salt with a pharmaceutically acceptable acid.
Claim 16
Dependent Claim
22 words
The method of claim 11 in which the compound of formula 1 is 1-[2-(dimethylamino)ethyl]-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or a pharmaceutically acceptable acid addition salt thereof.
Claim 17
Dependent Claim
22 words
The method of claim 11 in which the compound of formula 1 is 1,9-dimethyl-1-[2-(dimethylamino)ethyl]-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or a pharmaceutically acceptable acid addition salt thereof.
Claim 18
Dependent Claim
22 words
The method of claim 11 in which the compound of formula 1 is 1-[2-(dimethylamino)ethyl]-9-ethyl-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or a pharmaceutically acceptable acid addition salt thereof.
Claim 19
Dependent Claim
22 words
The method of claim 11 in which the compound of formula 1 is 1-[2-(dimethylamino)ethyl]-1-methyl-9-propyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or a pharmaceutically acceptable acid addition salt thereof.
Claim 20
Dependent Claim
22 words
The method of claim 11 in which the compound of formula 1 is 9-ethyl-1-methyl-1-[2-(methylamino)ethyl]-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or a pharmaceutically acceptable acid addition salt thereof.
Claim 21
Dependent Claim
23 words
The method of claim 11 in which the compound of formula 1 is (+)-or (-)-1-[2-(dimethylamino)ethyl]-9-ethyl-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or a pharmaceutically acceptable acid addition salt thereof.
Claim 22
Dependent Claim
22 words
The method of claim 11 in which the compound of formula 1 is 9-allyl-1-[2-(dimethylamino)ethyl]-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or a pharmaceutically acceptable acid addition salt thereof.
Claim 23
Dependent Claim
396 words
A pharmaceutical composition, which comprises: a compound selected from those of the formulae 1 and 1a ##STR106## in which R 1 is lower alkyl or lower cycloalkyl; R 2 . R 3 , R 4 and R 5 are the same or different selected from the group consisting of hydrogen and lower alkyl; R 6 is hydrogen, lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, nitro or halo; R 7 is hydrogen, lower alkyl, lower alkenyl, propargyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of formula --Alk--NR 8 R 9 wherein Alk is an alkylene selected from the group consisting of CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl, and R 8 and R 9 are either the same or different selected from the group consisting of hydrogen and lower alkyl, or R 8 is lower alkyl and R 9 is p-chlorophenacyl, or R 8 and R 9 together with the nitrogen atom to which they are joined form a heterocyclic amine radical selected from the group consisting of 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl, 4-(lower alkyl)-1-piperazinyl and 4-[hydroxy(lower)alkyl]-1-piperazinyl; X is thio; and Y is lower alkyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of formula --Alk--NR 8 R 9 wherein Alk is an alkylene selected from the group consisting of CR 10 R 11 , CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl and R 8 and R 9 are as defined herein; with the proviso that at least one of R 7 and Y is -Alk-NR 8 R 9 and that in the compounds of formula 1a, Y is --Alk NR 8 R 9 as defined herein; and the corresponding acid addition salt with a pharmaceutically acceptable acid; and a pharmaceutically acceptable carrier.
Claim 24
Dependent Claim
396 words
A pharmaceutical composition, which comprises: a compound selected from those of the formulae 1 and 1a ##STR106## in which R 1 is lower alkyl or lower cycloalkyl; R 2 . R 3 , R 4 and R 5 are the same or different selected from the group consisting of hydrogen and lower alkyl; R 6 is hydrogen, lower alkyl, hydroxy, lower alkoxy, lower alkanoyloxy, nitro or halo; R 7 is hydrogen, lower alkyl, lower alkenyl, propargyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of formula --Alk--NR 8 R 9 wherein Alk is an alkylene selected from the group consisting of CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl, and R 8 and R 9 are either the same or different selected from the group consisting of hydrogen and lower alkyl, or R 8 is lower alkyl and R 9 is p-chlorophenacyl, or R 8 and R 9 together with the nitrogen atom to which they are joined form a heterocyclic amine radical selected from the group consisting of 1-pyrrolidinyl, piperidino, morpholino, 1-piperazinyl, 4-(lower alkyl)-1-piperazinyl and 4-[hydroxy(lower)alkyl]-1-piperazinyl; X is thio; and Y is lower alkyl, phenyl(lower)alkyl or an amino(lower)alkyl radical of formula --Alk--NR 8 R 9 wherein Alk is an alkylene selected from the group consisting of CR 10 R 11 , CR 10 R 11 CR 12 R 13 , CR 10 R 11 CR 12 R 13 CR 14 R 15 and CR 10 R 11 CR 12 R 13 CR 14 R 15 CR 16 R 17 wherein R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 and R 17 are hydrogen or lower alkyl and R 8 and R 9 are as defined herein; with the proviso that at least one of R 7 and Y is -Alk-NR 8 R 9 and that in the compounds of formula 1a, Y is --Alk NR 8 R 9 as defined herein; and the corresponding acid addition salt with a pharmaceutically acceptable acid; and a pharmaceutically acceptable carrier.
Claim 25
Dependent Claim
21 words
The composition of claim 19 in which the compound of formula 1 is 1-[2-(dimethylamino)ethyl]-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or the oxalic acid addition salt thereof.
Claim 26
Dependent Claim
21 words
The composition of claim 19 in which the compound of formula 1 is 1,9-dimethyl-1-[2-(dimethylamino)ethyl]-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or the hydrochloric acid addition salt thereof.
Claim 27
Dependent Claim
21 words
The composition of claim 19 in which the compound of formula 1 is 1-[2-(dimethylamino)ethyl]-9-ethyl-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or the hydrochloric acid addition salt thereof.
Claim 28
Dependent Claim
21 words
The composition of claim 19 in which the compound of formula 1 is 1-[2-(dimethylamino)ethyl]-1-methyl-9-propyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or the hydrochloric acid addition salt thereof.
Claim 29
Dependent Claim
21 words
The composition of claim 19 in which the compound of formula 1 is 9-ethyl-1-methyl-1-[2-(methylamino)ethyl]-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or the hydrochloric acid addition salt thereof.
Claim 30
Dependent Claim
22 words
The composition of claim 22 in which the compound of formula 1 is (+)- or(-)-1-[2-(dimethylamino)ethyl]-9-ethyl-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or the hydrochloric acid addition salt thereof.
Claim 31
Dependent Claim
21 words
The composition of claim 19 in which the compound of formula 1 is 9-allyl-1-[2-(dimethylamino)ethyl]-1,3,4,9-tetrahydro-1-methyl-1,3,4,9-tetrahydrothiopyrano[3,4-b]indole, or the hydrochloric acid addition salt thereof.
References Cited (Backward Citations)
US3778449A
Cited
US3910954A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1980-01-18 | 1980-07-19 | 1981-01-18 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1984-01-18 | 1984-07-19 | 1985-01-18 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1988-01-18 | 1988-07-19 | 1989-01-18 | $7700.00 | Window Closed / Lapsed |