# US 4,399,141 A · 5-Alkyl or hydroxyalkyl substituted-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imines and anticonvulsant use thereof

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- Number: US 4,399,141 A
- Document ID: US4399141A
- Status: Granted
- Kind: A
- Application number: 06/272,864
- Filed: 1981-06-12
- Granted: 1983-08-16
- Earliest claimed: 1977-09-19
- Assignees: Merck & Co., Inc.
- Inventors: Paul Anderson; Marcia E. Christy; Ben E. Evans
- Web page: https://patentgrep.com/patent/US4399141A

## CPC

- C07D 295/096: with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
- C07C 45/56: from heterocyclic compounds (C07C45/55 takes precedence)
- C07D 295/116: with the doubly bound oxygen or sulfur atoms directly attached to a carbocyclic ring
- C07D 451/02: containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## Abstract

5-Substituted-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imines, derivatives and pharmaceutically acceptable salts thereof are useful as anticonvulsants.

## Claims

### Claim 1

A compound of the structural formula ##STR110## or a pharmaceutically acceptable salt thereof wherein: R is
(1) hydrogen,
(2) C.sub.1-5 alkyl,
(3) C.sub.2-5 alkenyl,
(4) phenyl-C.sub.1-3 alkyl,
(5) halophenyl-C.sub.1-3 alkyl,
(6) C.sub.1-3 alkylphenyl-C.sub.1-3 alkyl,
(7) C.sub.3-6 cycloalkyl,
(8) C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl,
(9) di(C.sub.1-3 alkyl)amino-C.sub.1-3 alkyl; or
(10) hydroxy;
R.sup.1 is
(1) hydrogen,
(2) C.sub.1-5 alkyl,
(3) C.sub.2-5 alkenyl,
(4) phenyl-C.sub.1-3 alkyl,
(5) C.sub.3-6 cycloalkyl
(6) C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl;
--CH.sub.2 R.sup.2 is
(1) methyl,
(2) ethyl or
(3) hydroxyethyl; and
R.sup.3 and R.sup.4 are independently
(1) hydrogen,
(2) halogen,
(3) C.sub.1-5 alkoxy,
(4) trifluoromethylthio,
(5) cyano,
(6) carboxy, or
(7) hydroxy.

### Claim 2 (depends on 1)

The compound of claim 1 wherein R.sup.1 is hydrogen.

### Claim 3 (depends on 1)

The compound of claim 1 wherein R.sup.1, R.sup.3 and R.sup.4 are hydrogen; R is hydrogen, C.sub.1-5 alkyl, C.sub.2-5 alkenyl or C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl; and --CH.sub.2 R.sup.2 is methyl or ethyl.

### Claim 4 (depends on 3)

The compound of claim 3 wherein R.sup.1, R.sup.3 and R.sup.4 are hydrogen, R is hydrogen, or C.sub.1-5 alkyl; and --CH.sub.2 R.sup.2 is methyl or ethyl.

### Claim 5 (depends on 4)

The compound of claim 4 which is racemic 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine, its optically active isomers, or a pharmaceutically acceptable salt thereof.

### Claim 6 (depends on 4)

The compound of claim 4 which is (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine or a pharmaceutically acceptable salt thereof.

### Claim 7

A pharmaceutical composition useful as an anticonvulsant, comprising a pharmaceutical carrier and an effective anticonvulsant amount of a compound of structural formula: ##STR111## or a pharmaceutically acceptable salt thereof wherein: R is
(1) hydrogen,
(2) C.sub.1-5 alkyl,
(3) C.sub.2-5 alkenyl,
(4) phenyl-C.sub.1-3 alkyl,
(5) halophenyl-C.sub.1-3 alkyl,
(6) C.sub.1-3 alkylphenyl-C.sub.1-3 alkyl,
(7) C.sub.3-6 cycloalkyl,
(8) C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl,
(9) di(C.sub.1-3 alkyl)amino-C.sub.1-3 alkyl; or
(10) hydroxy;
R.sup.1 is
(1) hydrogen,
(2) C.sub.1-5 alkyl,
(3) C.sub.2-5 alkenyl,
(4) phenyl-C.sub.1-3 alkyl,
(5) C.sub.3-6 cycloalkyl,
(6) C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl;
--CH.sub.2 R.sup.2 is
(1) methyl
(2) ethyl or
(3) hydroxyethyl; and
R.sup.3 and R.sup.4 are independently
(1) hydrogen,
(2) halogen,
(3) C.sub.1-5 alkoxy,
(4) trifluoromethylthio,
(5) cyano,
(6) carboxy, or
(7) hydroxy.

### Claim 8 (depends on 7)

The composition of claim 7 wherein R.sup.1 is hydrogen.

### Claim 9 (depends on 7)

The composition of claim 7 wherein R.sup.1, R.sup.3 and R.sup.4 are hydrogen; R is hydrogen, C.sub.1-5 alkyl, C.sub.2-5 alkenyl or C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl; and --CH.sub.2 R.sup.2 is methyl or ethyl.

### Claim 10 (depends on 9)

The composition of claim 9 wherein R.sup.1, R.sup.3 and R.sup.4 are hydrogen; R is hydrogen, or C.sub.1-5 alkyl; and --CH.sub.2 R.sup.2 is methyl or ethyl.

### Claim 11 (depends on 10)

The pharmaceutical composition of claim 10 wherein the compound is racemic 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine, its optically active isomers, or a pharmaceutically acceptable salt thereof.

### Claim 12 (depends on 10)

The pharmaceutical composition of claim 10 wherein the compound is (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine or a pharmaceutically acceptable salt thereof.

### Claim 13

A method of treating convulsions, comprising administering to a patient in need of such treatment an effective anticonvulsant amount of a compound of structural formula: ##STR112## or a pharmaceutical acceptable salt thereof wherein: R is
(1) hydrogen,
(2) C.sub.1-5 alkyl,
(3) C.sub.2-5 alkenyl,
(4) phenyl-C.sub.1-3 alkyl,
(5) halophenyl-C.sub.1-3 alkyl,
(6) C.sub.1-3 alkylphenyl-C.sub.1-3 alkyl,
(7) C.sub.3-6 cycloalkyl,
(8) C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl,
(9) di(C.sub.1-3 alkyl)amino-C.sub.1-3 alkyl; or
(10) hydroxy;
R.sup.1 is
(1) hydrogen,
(2) C.sub.1-5 alkyl
(3) C.sub.2-5 alkenyl,
(4) phenyl-C.sub.1-3 alkyl,
(5) C.sub.3-6 cycloalkyl,
(6) C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl;
--CH.sub.2 R.sup.2 is
(1) methyl,
(2) ethyl or
(3) hydroxyethyl; and
R.sup.3 and R.sup.4 are independently
(1) hydrogen,
(2) halogen,
(3) C.sub.1-5 alkoxy,
(4) trifluoromethylthio,
(5) cyano,
(6) carboxy, or
(7) hydroxy.

### Claim 14 (depends on 13)

The method of claim 13 wherein R.sup.1 is hydrogen.

### Claim 15 (depends on 14)

The method of claim 14 wherein R.sup.1, R.sup.3 and R.sup.4 are hydrogen; R is hydrogen, C.sub.1-5 alkyl, C.sub.2-5 alkenyl or C.sub.3-6 cycloalkyl-C.sub.1-3 alkyl; and --CH.sub.2 R.sup.2 is methyl or ethyl.

### Claim 16 (depends on 15)

The method of claim 15 wherein R.sup.1, R.sup.3 and R.sup.4 are hydrogen; R is hydrogen, or C.sub.1-5 alkyl; and --CH.sub.2 R.sup.2 is methyl or ethyl.

### Claim 17 (depends on 16)

The method of claim 16 wherein the compound is racemic 5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine, its optically active isomers, or a pharmaceutically acceptable salt thereof.

### Claim 18 (depends on 16)

The method of claim 16, wherein the compound is (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine or a pharmaceutically acceptable salt thereof.