Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
  • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
  • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D337/00—Heterocyclic compounds containing rings of more than six members having one sulfur atom as the only ring hetero atom
  • C07D337/02—Seven-membered rings
  • C07D337/06—Seven-membered rings condensed with carbocyclic rings or ring systems
  • C07D337/10—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with two six-membered rings
  • C07D337/14—[b,f]-condensed

Definitions

• 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.
• chlorpromazine which is chemically 2-chloro-10-(3-dimethylaminopropyl)-phenothiazine exhibit a high tranquilizing activity along with the cataleptic action.
• 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.
• the present invention mainly comprises new N-oxides of dibenzo ([b,f]thiepines of Formula I below:
• 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,
• R is selected from the group consisting of alkyl of 1-4 carbon atoms and hydroxy alkyl of 2-4 carbon atoms, and
• 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.
• the compounds of the present invention are produced by reacting the basic tertiary amine of the following Formula II:
• 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.
• 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.
• 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).
• 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.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Heterocyclic Compounds Containing Sulfur Atoms (AREA)

Applications Claiming Priority (1)

Publications (1)

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ID=5431258

Family Applications (1)

Country Status (11)

Cited By (3)

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• 0
  • BE BE759999D patent/BE759999A/xx unknown
• 1969
  • 1969-12-10 CS CS8111A patent/CS148851B1/cs unknown
• 1970
  • 1970-12-08 US US00096262A patent/US3830814A/en not_active Expired - Lifetime
  • 1970-12-09 CH CH1818670A patent/CH547307A/xx not_active IP Right Cessation
  • 1970-12-09 SE SE16679/70A patent/SE366747B/xx unknown
  • 1970-12-09 AT AT1106370A patent/AT297714B/de not_active IP Right Cessation
  • 1970-12-09 JP JP45109297A patent/JPS494463B1/ja active Pending
  • 1970-12-10 NL NL7018025A patent/NL7018025A/xx unknown
  • 1970-12-10 DE DE19702060903 patent/DE2060903B2/de active Granted
  • 1970-12-10 GB GB58794/70A patent/GB1277854A/en not_active Expired
  • 1970-12-10 FR FR7044576A patent/FR2081339B1/fr not_active Expired

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