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(en)N-OXIDES OF DIBENZO(B,F)THIEPINES AND SALTS THEREOF, THESE COMPOUNDS EXHIBITING A RELATIVELY HIGH CATAAEPTIC ACITIVITY WITH A RELATIVELY LOW CENTRAL SEDATIVE OR TRANQUILIZNG ACTION. THE INVENTION FURTHER RELATES TO THE PRODUCTION OF THESE NEW COMPOUNDS.
1.ApplicationNumber: US-9626270-A
1.PublishNumber: US-3830814-A
2.Date Publish: 19740820
3.Inventor: JILEK J,CS
PROTIVA M,CS
METYSOVA J,CS
POMYKACEK J,CS
4.Inventor Harmonized: JILEK J()
PROTIVA M()
METYSOVA J()
POMYKACEK J()
5.Country: US
6.Claims:
(en)N-OXIDES OF DIBENZO(B,F)THIEPINES AND SALTS THEREOF, THESE COMPOUNDS EXHIBITING A RELATIVELY HIGH CATAAEPTIC ACITIVITY WITH A RELATIVELY LOW CENTRAL SEDATIVE OR TRANQUILIZNG ACTION. THE INVENTION FURTHER RELATES TO THE PRODUCTION OF THESE NEW COMPOUNDS.
7.Description:
(en)United States Patent 3,830,814 N-OXIDES 0F DIBENZO[b,f]THIEPINES Jiri Jilek, Miroslav Protiva, Jirina Metysova, and Josef Pomykacek, Prague, Czechoslovakia, assignors to SPOFA, United Pharmaceutical Works, Prague, Czechoslovakia No Drawing. Filed Dec. 8, 1970, Ser. No. 96,262 Claims priority, application Czechoslovakia, Dec. 10, 1969, 8,111/69 Int. Cl. C07d 51/70 US. Cl. 260-268 TR 4 Claims ABSTRACT OF THE DISCLOSURE N-oxides of dibenzo[b,f]thiepines and salts thereof, these compounds exhibiting a relatively high cataleptic activity with a relatively low central sedative or tranquilizing action. The invention further relates to the production of these new compounds.
BACKGROUND OF THE INVENTION The known psychotropic preparations such as chlorpromazine which is chemically 2-chloro-10-(3-dimethylaminopropyl)-phenothiazine exhibit a high tranquilizing activity along with the cataleptic action. For the treatment of psychotic conditions of the schizophrenia type it is desirable to provide a cataleptic effect without a high degree of tranquilizing action. It is as to this problem that the present invention is directed.
SUMMARY OF THE INVENTION Generally speaking this invention relates to a new series of N-oxides of dibenzo[b,f]thiepines and the salts thereof, as well as the production of these compounds, these compounds exhibiting a relatively high cataleptic activity with relatively no tranquilizing action.
It is a primary object of the present invention to provide these new compounds and also to provide for the production of the same.
It is a further object of the present invention to provide such compounds with a high degree of cataleptic activity and a relatively low tranquilizing activity.
Other objects and advantages of the present invention would be apparent from a further reading of the specification and of the appended claims.
With the above and other objects in view, the present invention mainly comprises new N-oxides of dibenzo ([b,f]thiepines of Formula I below:
wherein R is selected from the group consisting of hydrogen, halogen, trifiuoromethy], alkyl of l-4 carbon atoms, alkoxy of 1-4 carbon atoms and alkylthio of 1-4 carbon atoms,
wherein R is selected from the group consisting of alkyl of 1-4 carbon atoms and hydroxy alkyl of 2-4 carbon atoms, and
wherein X is selected from the group consisting of sulfur, SO and S0 The present invention also relates to salts of the above compounds, particularly salts with nontoxic, physiologically compatible inorganic and organic compounds.
The above compounds exhibit a marked tranquilizing and psychotropic activity so that the same can be used ice as agents in the treatment of mental and nervous dis orders.
In the case of the compounds of the present invention it has been found that in comparison to the analogous tertiary amines the displacement of the equilibrium tranquilizing-cataleptic activity in favor of the cataleptic activity occurs, which from the standpoint of use is a particularly favorable characteristic in the treatment of psychotic conditions of the schizophrenia type.
Thus, for example, in the case of 8-chloro-10-[4-(3- hydroxypropyl)piperazino] 10,11 dihydrodibenzo[b,f] thiepine-N-oxide-dihydrochloride, the production of which is described in Example 4 it is found in the rotating rod test on mice (which is utilized as the criterion for cen tral sedative or tranquilizing activity) upon intravenous administration the average active dose ED is 2.1 mg./ kg, and in the catalepsis test on rats upon intraperitoneal administration is 2.0 mg./kg. The known neuroleptic preparation Chlorpromazine" in the same tests shows an ED value in the first test (tranquilizing) of 0.6 mg./ kg. and in the second test (cataleptic) of 8.6 mg./kg. Thus, while the compound of the present invention exhibits about one-fourth the tranquilizing activity of chlorpromazine, it is four times as active as the chlorpromazine in the cataleptic test. This disproportion of the two actions is even more markedly noticeable upon comparison of the compound of the present invention with Octoclothepin, that is with 8-chloro-10 (4-methylpiperazino)- 10,11-dihydrodibenzo [b,f]thiepine. The ED value of this substance in the above two tests is 0.06 mg./kg. for the tranquilizing test and 2.4 mg./kg. for the cataleptic test. It is apparent from these results that while exhibiting practically the same cataleptic activity, the new compound of the present invention has about ,6 the tranquilizing activity.
The compounds of the present invention are produced by reacting the basic tertiary amine of the following Formula II:
(II) X wherein R R and X have the same definitions as in Formula I, with hydrogen peroxide in an equivalent amount up to a -25% excess. The oxidation reaction is preferably carried out in ethanol, and the obtained base may be converted into the corresponding salt by reaction with the selected inorganic or organic acid.
The carrying out of the method is extremely simple. The oxidation reaction proceeds even at room temperature and the reaction is ended by heating to the boiling temperature of the reaction mixture. The obtained basic product exhibits, contrary to the starting tertiary amine, a marked hydrophilic characteristic and it crystallizes preponderantly in the form of the hydrate. The salts which are obtained by neutralization with inorganic or organic acids can be used to make preparations for different forms of administration.
DESCRIPTION OF PREFERRED EMBODIMENTS The invention is further illustrated in the following examples. The scope of the invention is not, however, meant to be limited to the specific details of the examples.
EXAMPLE 1 6.6 g. of 25% hydrogen peroxide are added to a warmed solution at 10.0 g. of 10-(4-methylpiperazino)-l0,1l-dihydrodibenzo[b,f]thiepine base in 65 ml. of ethanol and the reaction mixture is permitted to stand at room temperature overnight. It is then heated for 3 hours to boiling under refluxing and an additional hour with a small platinum prism for the purpose of decomposing the excess peroxide. After filtration the filtrate is mixed with 20 ml. water and the solution evaporated under reduced pressure. The remaining crystalline mixture is diluted with 60 ml. of water and is allowed to crystallize for 12 hours. The precipitated product is filtered off under suction, washed with a small amount of water and dried under vacuum over phosphorous pentoxide. There is obtained 7.4 g. (70% of the theoretical) of 10 (4 methylpiperazino)- 10,11 dihydrodibenzo[b,f]thiepine N oxide in the form of its dihydrate, which retains its water in crystallization even after recrystallization from benezene. The melting point is 110-112 C. After neutralization with hydrogen chloride in an ethanol-ether mixture the base is converted into the corresponding crystalline hydrochloride which crystallizes from ethanol-ether in the form of the hemihydrate and which melts at l78182 C.
EXAMPLE 2 2.0 ml. of 25% hydrogen peroxide are added to a solution of 3.45 g. of 8 chloro 10 (4 methylpiperazino)- 10,11 dihydrodibenzo [b,f] thiepine base in 18 ml. of 95% ethanol. The mixture is permitted to stand overnight at room temperature and it is then heated for 3 hours to boiling under refluxing, mixed with 30 ml. of water and evaporated under reduced pressure. The residue is mixed with an additional 50 ml. of water, the crystallized product is filtered 01f under suction and dried under vacuum over phosphorous pentoxide. There is obtained 3.4 g. of 8-chloro- 10 (4 methylpiperazino) 10,11 dihydrodibenzo [b,f] thiepine N oxide in the form of the monohydrate which retains its water of crystallization even after recrystallization from acetone or benzene. The analytically pure product melts at 129-131" C. By neutralization with hydrogen chloride in ethanol the base is converted to the corresponding monohydrochloride which melts at 198200 (ethanol) EXAMPLE 3 A solution of 7.6 g. of 8 methylthio 10 (4-methylpiperazino) 10,11 dihydrodibenzo[b,f]thiepine-base in 40 ml. of 95 ethanol is oxidized by means of 3.7 m1. of 25 hydrogen peroxide in analogous manner to the preceding examples. There is obtained in practically theoretical yield the 8-methylthio 10 (4 methylpiperazino)- 10,11 dihydrodibenzo[b,f]thiepine-N-oxide in the form of a syrupy hydrate which is dissolved in ethanol and neutralized with an ethanolic hydrogen chloride solution. There is thus obtained the crystalline dihydrochloride-dihydrate of the above product which melts at 176-178 C.
and which violently decomposes at above 185 C.
EXAMPLE 4 A solution of 3.5 g. of 8 chloro 10 [4 (3 hydroxypropyl)piperazino] 10,11 dihydrodibenzo[b,f]thiepine base in 18 ml. of 95% ethanol is oxidized with 2 ml. of 25 hydrogen peroxide in analogous manner to the preceding examples. There is obtained 2.1 g. of the pure monohydrate of 8 chloro 1O [4 (3 hydroxypropyl)- 'piperazino] 10,11 dihydrodibenzo[b,f]thiepine-N-oxide which melts at 156-159 C. (benzene). By neutralization with hydrogen chloride in ethanol the base is converted to the corresponding dihydrochloride-hemihydrate which melts at 155158 C. (ethanol).
EXAMPLE 5 A solution of 4.2 g. of 8-chloro-10-(4-methylpiperazino)-10,1 1-dihydrodibenzo[b,f]thiepine-S-oxide base in 20 ml. of 95% ethanol is oxidized with 2.5 ml. of 25 hydrogen peroxide similarly to the preceding examples. By recrystallization of the crude product from 30 ml. of acetone there is obtained pure 8-chloro-l0-(4-methylpiperazino)-10,1l-dihydrodibenzo[b,f]thiepine-5,N oxide in the form of the sesquihydrate in the yield of 3.5 g. which corresponds to 75% of the theoretical, and having a melting point of l53 C. By heating above the melting point the substance again solidifies to a crystalline material and now melts at ZOO-207 C. By neutralization with hydrogen chloride in ethanol there is obtained the crystalline dihydrochloride which melts at 203207 C. (waterethanol).
EXAMPLE 6 In an analogous manner to the preceding examples a solution of 3.5 g. of 8-chloro-10-(4-methylpiperazino)- 10,11-dihydrodibenzo[b,f]thiepine-5,5-dioxide base in 30 ml. of ethanol is oxidized with 2.3 ml. of 25 hydrogen peroxide. After recrystallization of the crude product from 5 ml. of water there is obtained 2.5 g. (68% of the theoretical) of crystalline 8-chloro-10-(4-methylpiperazino)- 10,11 dihydrodibenzo[b,f]thiepine-5,5,N-trioxide-monohydrate which melts at 203-206 C. By neutralization with hydrogen chloride in ethanol the corresponding dihydrochloride is obtained which melts sharply with decomposition at 180-188" C. (water-ethanol).
While the invention has been illustrated in particular with respect to the production of certain specific compounds, it is apparent that variations and modifications of the invention can be made without departing from the spirit or scope thereof.
What is claimed is:
1. A compound of the formula wherein R is hydrogen, halogen, alkyl of 1-4 carbon atoms, and alkoxy of 1-4 carbon atoms; R is alkyl of 1-4 carbon atoms or monohydroxy alkyl of 2 to 4 carbon atoms and their pharmaceutically acceptable acid addition salts.
2. Compound according to claim 1 wherein said compound is selected from the group consisting of 10-(4-methylpiperazino)-10,11-dihydrodibenzo[b,f]thiepine N oxide, the dihydrate thereof and the dihydrochloride-hemihydrate thereof.
3. Compound according to claim 1 wherein said compound is selected from the group consisting of 8-chloro- 10 (4 methylpiperazino) 10,11 dihydrodibenzo [b,f] thiepine-N-oxide, the monohydrate thereof and the hydrochloride thereof.
4. Compound according to claim 1 wherein said compound is selected from the group consisting of 8-chloro- 10-[4-(3-hydroxypropyl)piperazino] 10,11 dihydrodibenzo [b,'f] thiepine-N-oxide, the monohydrate thereof and the dihydrochloride-hemihydrate thereof.
References Cited UNITED STATES PATENTS 3,047,579 7/ 1962 Witman 260289 R 3,337,554 8/1967 Jilek 260268 T R 3,341,533 8/1967 Yale 260268 T R 3,509,154 4/1970 Fouche 260268 T R 3,563,993 2/1971 Schindler 260268 T R 3,351,599 11/1967 Protiva 260268 T R DONALD G. DAUS, Primary Examiner US. Cl. X.R. 424-250
1.PublishNumber: US-3830814-A
2.Date Publish: 19740820
3.Inventor: JILEK J,CS
PROTIVA M,CS
METYSOVA J,CS
POMYKACEK J,CS
4.Inventor Harmonized: JILEK J()
PROTIVA M()
METYSOVA J()
POMYKACEK J()
5.Country: US
6.Claims:
(en)N-OXIDES OF DIBENZO(B,F)THIEPINES AND SALTS THEREOF, THESE COMPOUNDS EXHIBITING A RELATIVELY HIGH CATAAEPTIC ACITIVITY WITH A RELATIVELY LOW CENTRAL SEDATIVE OR TRANQUILIZNG ACTION. THE INVENTION FURTHER RELATES TO THE PRODUCTION OF THESE NEW COMPOUNDS.
7.Description:
(en)United States Patent 3,830,814 N-OXIDES 0F DIBENZO[b,f]THIEPINES Jiri Jilek, Miroslav Protiva, Jirina Metysova, and Josef Pomykacek, Prague, Czechoslovakia, assignors to SPOFA, United Pharmaceutical Works, Prague, Czechoslovakia No Drawing. Filed Dec. 8, 1970, Ser. No. 96,262 Claims priority, application Czechoslovakia, Dec. 10, 1969, 8,111/69 Int. Cl. C07d 51/70 US. Cl. 260-268 TR 4 Claims ABSTRACT OF THE DISCLOSURE N-oxides of dibenzo[b,f]thiepines and salts thereof, these compounds exhibiting a relatively high cataleptic activity with a relatively low central sedative or tranquilizing action. The invention further relates to the production of these new compounds.
BACKGROUND OF THE INVENTION The known psychotropic preparations such as chlorpromazine which is chemically 2-chloro-10-(3-dimethylaminopropyl)-phenothiazine exhibit a high tranquilizing activity along with the cataleptic action. For the treatment of psychotic conditions of the schizophrenia type it is desirable to provide a cataleptic effect without a high degree of tranquilizing action. It is as to this problem that the present invention is directed.
SUMMARY OF THE INVENTION Generally speaking this invention relates to a new series of N-oxides of dibenzo[b,f]thiepines and the salts thereof, as well as the production of these compounds, these compounds exhibiting a relatively high cataleptic activity with relatively no tranquilizing action.
It is a primary object of the present invention to provide these new compounds and also to provide for the production of the same.
It is a further object of the present invention to provide such compounds with a high degree of cataleptic activity and a relatively low tranquilizing activity.
Other objects and advantages of the present invention would be apparent from a further reading of the specification and of the appended claims.
With the above and other objects in view, the present invention mainly comprises new N-oxides of dibenzo ([b,f]thiepines of Formula I below:
wherein R is selected from the group consisting of hydrogen, halogen, trifiuoromethy], alkyl of l-4 carbon atoms, alkoxy of 1-4 carbon atoms and alkylthio of 1-4 carbon atoms,
wherein R is selected from the group consisting of alkyl of 1-4 carbon atoms and hydroxy alkyl of 2-4 carbon atoms, and
wherein X is selected from the group consisting of sulfur, SO and S0 The present invention also relates to salts of the above compounds, particularly salts with nontoxic, physiologically compatible inorganic and organic compounds.
The above compounds exhibit a marked tranquilizing and psychotropic activity so that the same can be used ice as agents in the treatment of mental and nervous dis orders.
In the case of the compounds of the present invention it has been found that in comparison to the analogous tertiary amines the displacement of the equilibrium tranquilizing-cataleptic activity in favor of the cataleptic activity occurs, which from the standpoint of use is a particularly favorable characteristic in the treatment of psychotic conditions of the schizophrenia type.
Thus, for example, in the case of 8-chloro-10-[4-(3- hydroxypropyl)piperazino] 10,11 dihydrodibenzo[b,f] thiepine-N-oxide-dihydrochloride, the production of which is described in Example 4 it is found in the rotating rod test on mice (which is utilized as the criterion for cen tral sedative or tranquilizing activity) upon intravenous administration the average active dose ED is 2.1 mg./ kg, and in the catalepsis test on rats upon intraperitoneal administration is 2.0 mg./kg. The known neuroleptic preparation Chlorpromazine" in the same tests shows an ED value in the first test (tranquilizing) of 0.6 mg./ kg. and in the second test (cataleptic) of 8.6 mg./kg. Thus, while the compound of the present invention exhibits about one-fourth the tranquilizing activity of chlorpromazine, it is four times as active as the chlorpromazine in the cataleptic test. This disproportion of the two actions is even more markedly noticeable upon comparison of the compound of the present invention with Octoclothepin, that is with 8-chloro-10 (4-methylpiperazino)- 10,11-dihydrodibenzo [b,f]thiepine. The ED value of this substance in the above two tests is 0.06 mg./kg. for the tranquilizing test and 2.4 mg./kg. for the cataleptic test. It is apparent from these results that while exhibiting practically the same cataleptic activity, the new compound of the present invention has about ,6 the tranquilizing activity.
The compounds of the present invention are produced by reacting the basic tertiary amine of the following Formula II:
(II) X wherein R R and X have the same definitions as in Formula I, with hydrogen peroxide in an equivalent amount up to a -25% excess. The oxidation reaction is preferably carried out in ethanol, and the obtained base may be converted into the corresponding salt by reaction with the selected inorganic or organic acid.
The carrying out of the method is extremely simple. The oxidation reaction proceeds even at room temperature and the reaction is ended by heating to the boiling temperature of the reaction mixture. The obtained basic product exhibits, contrary to the starting tertiary amine, a marked hydrophilic characteristic and it crystallizes preponderantly in the form of the hydrate. The salts which are obtained by neutralization with inorganic or organic acids can be used to make preparations for different forms of administration.
DESCRIPTION OF PREFERRED EMBODIMENTS The invention is further illustrated in the following examples. The scope of the invention is not, however, meant to be limited to the specific details of the examples.
EXAMPLE 1 6.6 g. of 25% hydrogen peroxide are added to a warmed solution at 10.0 g. of 10-(4-methylpiperazino)-l0,1l-dihydrodibenzo[b,f]thiepine base in 65 ml. of ethanol and the reaction mixture is permitted to stand at room temperature overnight. It is then heated for 3 hours to boiling under refluxing and an additional hour with a small platinum prism for the purpose of decomposing the excess peroxide. After filtration the filtrate is mixed with 20 ml. water and the solution evaporated under reduced pressure. The remaining crystalline mixture is diluted with 60 ml. of water and is allowed to crystallize for 12 hours. The precipitated product is filtered off under suction, washed with a small amount of water and dried under vacuum over phosphorous pentoxide. There is obtained 7.4 g. (70% of the theoretical) of 10 (4 methylpiperazino)- 10,11 dihydrodibenzo[b,f]thiepine N oxide in the form of its dihydrate, which retains its water in crystallization even after recrystallization from benezene. The melting point is 110-112 C. After neutralization with hydrogen chloride in an ethanol-ether mixture the base is converted into the corresponding crystalline hydrochloride which crystallizes from ethanol-ether in the form of the hemihydrate and which melts at l78182 C.
EXAMPLE 2 2.0 ml. of 25% hydrogen peroxide are added to a solution of 3.45 g. of 8 chloro 10 (4 methylpiperazino)- 10,11 dihydrodibenzo [b,f] thiepine base in 18 ml. of 95% ethanol. The mixture is permitted to stand overnight at room temperature and it is then heated for 3 hours to boiling under refluxing, mixed with 30 ml. of water and evaporated under reduced pressure. The residue is mixed with an additional 50 ml. of water, the crystallized product is filtered 01f under suction and dried under vacuum over phosphorous pentoxide. There is obtained 3.4 g. of 8-chloro- 10 (4 methylpiperazino) 10,11 dihydrodibenzo [b,f] thiepine N oxide in the form of the monohydrate which retains its water of crystallization even after recrystallization from acetone or benzene. The analytically pure product melts at 129-131" C. By neutralization with hydrogen chloride in ethanol the base is converted to the corresponding monohydrochloride which melts at 198200 (ethanol) EXAMPLE 3 A solution of 7.6 g. of 8 methylthio 10 (4-methylpiperazino) 10,11 dihydrodibenzo[b,f]thiepine-base in 40 ml. of 95 ethanol is oxidized by means of 3.7 m1. of 25 hydrogen peroxide in analogous manner to the preceding examples. There is obtained in practically theoretical yield the 8-methylthio 10 (4 methylpiperazino)- 10,11 dihydrodibenzo[b,f]thiepine-N-oxide in the form of a syrupy hydrate which is dissolved in ethanol and neutralized with an ethanolic hydrogen chloride solution. There is thus obtained the crystalline dihydrochloride-dihydrate of the above product which melts at 176-178 C.
and which violently decomposes at above 185 C.
EXAMPLE 4 A solution of 3.5 g. of 8 chloro 10 [4 (3 hydroxypropyl)piperazino] 10,11 dihydrodibenzo[b,f]thiepine base in 18 ml. of 95% ethanol is oxidized with 2 ml. of 25 hydrogen peroxide in analogous manner to the preceding examples. There is obtained 2.1 g. of the pure monohydrate of 8 chloro 1O [4 (3 hydroxypropyl)- 'piperazino] 10,11 dihydrodibenzo[b,f]thiepine-N-oxide which melts at 156-159 C. (benzene). By neutralization with hydrogen chloride in ethanol the base is converted to the corresponding dihydrochloride-hemihydrate which melts at 155158 C. (ethanol).
EXAMPLE 5 A solution of 4.2 g. of 8-chloro-10-(4-methylpiperazino)-10,1 1-dihydrodibenzo[b,f]thiepine-S-oxide base in 20 ml. of 95% ethanol is oxidized with 2.5 ml. of 25 hydrogen peroxide similarly to the preceding examples. By recrystallization of the crude product from 30 ml. of acetone there is obtained pure 8-chloro-l0-(4-methylpiperazino)-10,1l-dihydrodibenzo[b,f]thiepine-5,N oxide in the form of the sesquihydrate in the yield of 3.5 g. which corresponds to 75% of the theoretical, and having a melting point of l53 C. By heating above the melting point the substance again solidifies to a crystalline material and now melts at ZOO-207 C. By neutralization with hydrogen chloride in ethanol there is obtained the crystalline dihydrochloride which melts at 203207 C. (waterethanol).
EXAMPLE 6 In an analogous manner to the preceding examples a solution of 3.5 g. of 8-chloro-10-(4-methylpiperazino)- 10,11-dihydrodibenzo[b,f]thiepine-5,5-dioxide base in 30 ml. of ethanol is oxidized with 2.3 ml. of 25 hydrogen peroxide. After recrystallization of the crude product from 5 ml. of water there is obtained 2.5 g. (68% of the theoretical) of crystalline 8-chloro-10-(4-methylpiperazino)- 10,11 dihydrodibenzo[b,f]thiepine-5,5,N-trioxide-monohydrate which melts at 203-206 C. By neutralization with hydrogen chloride in ethanol the corresponding dihydrochloride is obtained which melts sharply with decomposition at 180-188" C. (water-ethanol).
While the invention has been illustrated in particular with respect to the production of certain specific compounds, it is apparent that variations and modifications of the invention can be made without departing from the spirit or scope thereof.
What is claimed is:
1. A compound of the formula wherein R is hydrogen, halogen, alkyl of 1-4 carbon atoms, and alkoxy of 1-4 carbon atoms; R is alkyl of 1-4 carbon atoms or monohydroxy alkyl of 2 to 4 carbon atoms and their pharmaceutically acceptable acid addition salts.
2. Compound according to claim 1 wherein said compound is selected from the group consisting of 10-(4-methylpiperazino)-10,11-dihydrodibenzo[b,f]thiepine N oxide, the dihydrate thereof and the dihydrochloride-hemihydrate thereof.
3. Compound according to claim 1 wherein said compound is selected from the group consisting of 8-chloro- 10 (4 methylpiperazino) 10,11 dihydrodibenzo [b,f] thiepine-N-oxide, the monohydrate thereof and the hydrochloride thereof.
4. Compound according to claim 1 wherein said compound is selected from the group consisting of 8-chloro- 10-[4-(3-hydroxypropyl)piperazino] 10,11 dihydrodibenzo [b,'f] thiepine-N-oxide, the monohydrate thereof and the dihydrochloride-hemihydrate thereof.
References Cited UNITED STATES PATENTS 3,047,579 7/ 1962 Witman 260289 R 3,337,554 8/1967 Jilek 260268 T R 3,341,533 8/1967 Yale 260268 T R 3,509,154 4/1970 Fouche 260268 T R 3,563,993 2/1971 Schindler 260268 T R 3,351,599 11/1967 Protiva 260268 T R DONALD G. DAUS, Primary Examiner US. Cl. X.R. 424-250
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