US4112112A
Expired / Lapsed
US
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Pyrrolo[2,1-b] [3]benzazepines useful for producing a skeletal muscle relaxing or tranquilizing effect
Assignee: Merck and Co Inc
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Filing: 1977-06-06
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Granted: 1978-09-05
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Expires: 1997-06-06
Abstract
Abstract 11-Aminopropylidene-Pyrrolo[2,1-b] [3]benzazepines are disclosed to have pharmaceutical utility as skeletal muscle relaxants and tranquilizers. They are prepared by a Grignard reaction on pyrrolo[2,1-b] [3]benzazapin-11-ones followed by dehydration, or by a Wittig reaction on the same ketones.
Inventors
- 👤 Clarence Stanley Rooney
- 👤 Joshua Rokach
- 👤 Joseph George Atkinson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-04 17:29
CPC Classifications
C; C07; C07D; C07D207/00; C07D207/02; C07D207/30; C07D207/32; C07D207/325; C07D207/327; C07D207/34; C07D207/36; C07D207/42; C07D217/00; C07D217/22; C07D217/24; C07D487/00; C07D487/02; C07D487/04
Claims Analysis
Total Claims: 20
Claim 1
Independent Claim
159 words
A compound of structural formula: ##STR27## or pharmaceutically acceptable salt thereof, wherein the dotted line represents saturation or unsaturation; X and Y are independently selected from (1) hydrogen (2) halo, (3) formyl, (4) C 2-6 -alkanoyl, (5) C 1-5 -alkyl, (6) (C 1-5 -alkoxy)carbonyl, (7) hydroxy-C 1-3 -alkyl, (8) trifluoromethyl (9) C 1-3 -alkoxy (10) cyano, (11) trifluoromethylthio, (12) C 1-3 -alkylthio, (13) C 1-3 -alkylsulfonyl, (14) trifluoromethylsulfonyl, (15) C 1-3 -alkylsulfinyl, (16) trifluoromethylsulfinyl, (17) amino, (18) C 2-6 -alkanoylamino, (19) C 1-3 -alkylamino, (20) di(C 1-3 alkyl)amino, (21) hydroxy, (22) N-C 1-3 -alkylcarbamoyl, (23) N,N-di(C 1-3 alkyl)carbamoyl, (24) nitro, (25) di(C 1-3 alkyl)sulfamoyl, (26) C 1-3 alkoxycarbonylamino, and (27) N-C 1-3 alkylcarbamoyloxy; and R 1 and R 2 are independently selected from (1) hydrogen, (2) C 1-3 -alkyl, (3) C 2-5 alkenyl, and (4) C 3-6 -cycloalkyl, or R 1 and R 2 joined together form with the nitrogen to which they are attached 1-piperidyl, 1-pyrrolidyl, or 4-morpholinyl.
Claim 2
Dependent Claim
159 words
A compound of structural formula: ##STR27## or pharmaceutically acceptable salt thereof, wherein the dotted line represents saturation or unsaturation; X and Y are independently selected from (1) hydrogen (2) halo, (3) formyl, (4) C 2-6 -alkanoyl, (5) C 1-5 -alkyl, (6) (C 1-5 -alkoxy)carbonyl, (7) hydroxy-C 1-3 -alkyl, (8) trifluoromethyl (9) C 1-3 -alkoxy (10) cyano, (11) trifluoromethylthio, (12) C 1-3 -alkylthio, (13) C 1-3 -alkylsulfonyl, (14) trifluoromethylsulfonyl, (15) C 1-3 -alkylsulfinyl, (16) trifluoromethylsulfinyl, (17) amino, (18) C 2-6 -alkanoylamino, (19) C 1-3 -alkylamino, (20) di(C 1-3 alkyl)amino, (21) hydroxy, (22) N-C 1-3 -alkylcarbamoyl, (23) N,N-di(C 1-3 alkyl)carbamoyl, (24) nitro, (25) di(C 1-3 alkyl)sulfamoyl, (26) C 1-3 alkoxycarbonylamino, and (27) N-C 1-3 alkylcarbamoyloxy; and R 1 and R 2 are independently selected from (1) hydrogen, (2) C 1-3 -alkyl, (3) C 2-5 alkenyl, and (4) C 3-6 -cycloalkyl, or R 1 and R 2 joined together form with the nitrogen to which they are attached 1-piperidyl, 1-pyrrolidyl, or 4-morpholinyl.
Claim 3
Dependent Claim
25 words
The compound of claim 1 wherein one of X and Y is hydrogen, and the other is hydrogen, cyano, formyl, C 2-6 alkanoyl, or chloro.
Claim 4
Dependent Claim
20 words
The compound of claim 2 wherein X is hydrogen, Y is 9-chloro and R 1 and R 2 are methyl.
Claim 5
Dependent Claim
14 words
The compound of claim 3 which is (E)-9-chloro-11-(3-dimethylaminopropylidene)-6,11-dihydro-5H-pyrrolo[2,1-b][3]benzazepine or a pharmaceutically acceptable salt thereof.
Claim 6
Dependent Claim
14 words
The compound of claim 3 which is (E)-9-chloro-11-(3-dimethylaminopropylidene)-11H-pyrrolo[2,1-b][3]benzazepine or a pharmaceutically acceptable salt thereof.
Claim 7
Dependent Claim
141 words
A compound of structural formula: ##STR28## wherein the dotted line represents unsaturation or saturation; X.sub.α and Y.sub.α are independently selected from (1) hydrogen, (2) halo, (3) C 2-6 -alkanoyl, (4) C 1-5 -alkyl, (5) (C 1-5 -alkoxy)carbonyl, (6) hydroxy-C 1-3 -alkyl, (7) trifluoromethyl (8) C 1-3 -alkoxy, (9) cyano, (10) trifluoromethylthio, (11) C 1-3 -alkylthio, (12) C 1-3 -alkylsulfonyl, (13) trifluoromethylsulfonyl, (14) C 1-3 -alkylsulfinyl, (15) trifluoromethylsulfinyl, (16) amino, (17) C 2-6 -alkanoylamino, (18) C 1-3 -alkylamino, (19) di(C 1-3 -alkyl)amino, (20) hydroxy, (21) N-C 1-3 -alkylcarbamoyl, (22) N,N-di(C 1-3 -alkyl)carbamoyl, (23) nitro, (24) di(C 1-3 -alkyl)sulfamoyl, (25) C 1-3 -alkoxycarbonylamino, and (26) N-C 1-3 -alkylcarbamoyloxy; and R.sub.α 1 and R.sub.α 2 are independently selected from (1) C 1-3 -alkyl, (2) C 2-5 -alkenyl, and (3) C 3-6 -cycloalkyl, or R.sub.α 1 and R.sub.α 2 together represent 1-piperidyl, 1-pyrrolidyl or 4-morpholinyl.
Claim 8
Dependent Claim
141 words
A compound of structural formula: ##STR28## wherein the dotted line represents unsaturation or saturation; X.sub.α and Y.sub.α are independently selected from (1) hydrogen, (2) halo, (3) C 2-6 -alkanoyl, (4) C 1-5 -alkyl, (5) (C 1-5 -alkoxy)carbonyl, (6) hydroxy-C 1-3 -alkyl, (7) trifluoromethyl (8) C 1-3 -alkoxy, (9) cyano, (10) trifluoromethylthio, (11) C 1-3 -alkylthio, (12) C 1-3 -alkylsulfonyl, (13) trifluoromethylsulfonyl, (14) C 1-3 -alkylsulfinyl, (15) trifluoromethylsulfinyl, (16) amino, (17) C 2-6 -alkanoylamino, (18) C 1-3 -alkylamino, (19) di(C 1-3 -alkyl)amino, (20) hydroxy, (21) N-C 1-3 -alkylcarbamoyl, (22) N,N-di(C 1-3 -alkyl)carbamoyl, (23) nitro, (24) di(C 1-3 -alkyl)sulfamoyl, (25) C 1-3 -alkoxycarbonylamino, and (26) N-C 1-3 -alkylcarbamoyloxy; and R.sub.α 1 and R.sub.α 2 are independently selected from (1) C 1-3 -alkyl, (2) C 2-5 -alkenyl, and (3) C 3-6 -cycloalkyl, or R.sub.α 1 and R.sub.α 2 together represent 1-piperidyl, 1-pyrrolidyl or 4-morpholinyl.
Claim 9
Dependent Claim
24 words
The compound of claim 6 wherein one of X.sub.α and Y.sub.α is hydrogen, and the other is hydrogen, cyano, C 2-6 alkanoyl or chloro.
Claim 10
Dependent Claim
20 words
The compound of claim 6 wherein X.sub.α is hydrogen, Y.sub.α is 9-chloro, and R.sub.α 1 and R.sub.α 2 are methyl.
Claim 11
Dependent Claim
179 words
A pharmaceutical composition for producing a skeletal muscle relaxing or tranquilizing effect comprising a pharmaceutical carrier and an effective amount of a compound of formula: ##STR29## or pharmaceutically acceptable salt thereof wherein the dotted line represents saturation or unsaturation; X and Y are independently selected from (1) hydrogen (2) halo, (3) formyl, (4) C 2-6 -alkanoyl, (5) C 1-5 -alkyl, (6) (C 1-5 -alkoxy)carbonyl, (7) hydroxy-C 1-3 alkyl, (8) trifluoromethyl (9) C 1-3 -alkoxy, (10) cyano, (11) trifluoromethylthio, (12) C 1-3 -alkylthio, (13) C 1-3 -alkylsulfonyl, (14) trifluoromethylsulfonyl, (15) C 1-3 -alkylsulfinyl, (16) trifluoromethylsulfinyl, (17) amino, (18) C 2-6 -alkanoylamino, (19) C 1-3 -alkylamino, (20) di(C 1-3 -alkyl)amino, (21) hydroxy, (22) N-C 1-3 -alkylcarbamoyl, (23) N,N-di(C 1-3 -alkyl)carbamoyl, (24) nitro, (25) di(C 1-3 -alkyl)sulfamoyl, (26) C 1-3 -alkoxycarbonylamino, and (27) N-C 1-3 -alkylcarbamoyloxy; and R 1 and R 2 are independently selected from (1) hydrogen, (2) C 1-3 -alkyl, (3) C 2-5 -alkenyl, and (4) C 3-6 -cycloalkyl, or R 1 and R 2 joined together form with the nitrogen to which they are attached 1-piperidyl, 1-pyrrolidyl, or 4-morpholinyl.
Claim 12
Dependent Claim
179 words
A pharmaceutical composition for producing a skeletal muscle relaxing or tranquilizing effect comprising a pharmaceutical carrier and an effective amount of a compound of formula: ##STR29## or pharmaceutically acceptable salt thereof wherein the dotted line represents saturation or unsaturation; X and Y are independently selected from (1) hydrogen (2) halo, (3) formyl, (4) C 2-6 -alkanoyl, (5) C 1-5 -alkyl, (6) (C 1-5 -alkoxy)carbonyl, (7) hydroxy-C 1-3 alkyl, (8) trifluoromethyl (9) C 1-3 -alkoxy, (10) cyano, (11) trifluoromethylthio, (12) C 1-3 -alkylthio, (13) C 1-3 -alkylsulfonyl, (14) trifluoromethylsulfonyl, (15) C 1-3 -alkylsulfinyl, (16) trifluoromethylsulfinyl, (17) amino, (18) C 2-6 -alkanoylamino, (19) C 1-3 -alkylamino, (20) di(C 1-3 -alkyl)amino, (21) hydroxy, (22) N-C 1-3 -alkylcarbamoyl, (23) N,N-di(C 1-3 -alkyl)carbamoyl, (24) nitro, (25) di(C 1-3 -alkyl)sulfamoyl, (26) C 1-3 -alkoxycarbonylamino, and (27) N-C 1-3 -alkylcarbamoyloxy; and R 1 and R 2 are independently selected from (1) hydrogen, (2) C 1-3 -alkyl, (3) C 2-5 -alkenyl, and (4) C 3-6 -cycloalkyl, or R 1 and R 2 joined together form with the nitrogen to which they are attached 1-piperidyl, 1-pyrrolidyl, or 4-morpholinyl.
Claim 13
Dependent Claim
21 words
The pharmaceutical composition of claim 9, wherein X is hydrogen, Y is 9-chloro and R 1 and R 2 are methyl.
Claim 14
Dependent Claim
16 words
The composition of claim 10 wherein the compound is (E)-9-chloro-11-(3-dimethylaminopropylidene)-6,11-dihydro-5H-pyrrolo[2,1-b][3]-benzazepine or a pharmaceutically acceptable salt thereof.
Claim 15
Dependent Claim
15 words
The composition of claim 10 wherein the compound is (E)-9-chloro-11-(3-dimethylaminopropylidene)-11H-pyrrolo[2,1-b][3]benzazepine or pharmaceutically acceptable salt thereof.
Claim 16
Independent Claim
185 words
A method of producing a skeletal muscle relaxant or tranquilizing effect in a patient in need of such treatment comprising the administration of an effective amount of a compound of formula: ##STR30## or pharmaceutically acceptable salt thereof, wherein the dotted line represents saturation or unsaturation; X and Y are independently selected from (1) hydrogen (2) halo, (3) formyl, (4) C 2-6 -alkanoyl, (5) C 1-5 -alkyl, (6) (C 1-5 -alkoxy)carbonyl, (7) hydroxy-C 1-3 -alkyl, (8) trifluoromethyl (9) C 1-3 -alkoxy (10) cyano, (11) trifluoromethylthio, (12) C 1-3 -alkylthio, (13) C 1-3 -alkylsulfonyl, (14) trifluoromethylsulfonyl, (15) C 1-3 -alkylsulfinyl, (16) trifluoromethylsulfinyl, (17) amino, (18) C 2-6 -alkanoylamino, (19) C 1-3 -alkylamino, (20) di(C 1-3 -alkyl)amino, (21) hydroxy, (22) N-C 1-3 -alkylcarbamoyl, (23) N,N-di(C 1-3 -alkyl)carbamoyl, (24) nitro, (25) di(C 1-3 -alkyl)sulfamoyl, (26) C 1-3 -alkoxycarbonylamino, and (27) N-C 1-3 -alkylcarbamoyloxy; and R 1 and R 2 are independently selected from (1) hydrogen, (2) C 1-3 -alkyl, (3) C 2-5 -alkenyl, and (4) C 3-6 -cycloalkyl, or R 1 and R 2 joined together form with the nitrogen to which they are attached 1-piperidyl, 1-pyrrolidyl, or 4-morpholinyl.
Claim 17
Independent Claim
185 words
A method of producing a skeletal muscle relaxant or tranquilizing effect in a patient in need of such treatment comprising the administration of an effective amount of a compound of formula: ##STR30## or pharmaceutically acceptable salt thereof, wherein the dotted line represents saturation or unsaturation; X and Y are independently selected from (1) hydrogen (2) halo, (3) formyl, (4) C 2-6 -alkanoyl, (5) C 1-5 -alkyl, (6) (C 1-5 -alkoxy)carbonyl, (7) hydroxy-C 1-3 -alkyl, (8) trifluoromethyl (9) C 1-3 -alkoxy (10) cyano, (11) trifluoromethylthio, (12) C 1-3 -alkylthio, (13) C 1-3 -alkylsulfonyl, (14) trifluoromethylsulfonyl, (15) C 1-3 -alkylsulfinyl, (16) trifluoromethylsulfinyl, (17) amino, (18) C 2-6 -alkanoylamino, (19) C 1-3 -alkylamino, (20) di(C 1-3 -alkyl)amino, (21) hydroxy, (22) N-C 1-3 -alkylcarbamoyl, (23) N,N-di(C 1-3 -alkyl)carbamoyl, (24) nitro, (25) di(C 1-3 -alkyl)sulfamoyl, (26) C 1-3 -alkoxycarbonylamino, and (27) N-C 1-3 -alkylcarbamoyloxy; and R 1 and R 2 are independently selected from (1) hydrogen, (2) C 1-3 -alkyl, (3) C 2-5 -alkenyl, and (4) C 3-6 -cycloalkyl, or R 1 and R 2 joined together form with the nitrogen to which they are attached 1-piperidyl, 1-pyrrolidyl, or 4-morpholinyl.
Claim 18
Dependent Claim
20 words
The method of claim 13 wherein X is hydrogen, Y is 9-chloro and R 1 and R 2 are methyl.
Claim 19
Dependent Claim
16 words
The method of claim 14 wherein the compound is (E)-9-chloro-11-(3-dimethylaminopropylidene)-6,11-dihydro-5H-pyrrolo[2,1-b][3]benzazepine or a pharmaceutically acceptable salt thereof.
Claim 20
Dependent Claim
15 words
The method of claim 14 wherein the compound is (E)-9-chloro-11-(3-dimethylaminopropylidene)-11H-pyrrolo[2,1-b][3]benzazepine or pharmaceutically acceptable salt thereof.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-09-04 | 1982-03-06 | 1982-09-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-09-04 | 1986-03-06 | 1986-09-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-09-04 | 1990-03-06 | 1990-09-05 | $7700.00 | Window Closed / Lapsed |