Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
  • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
  • C07D495/04—Ortho-condensed systems
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
  • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
  • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
  • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D333/30—Hetero atoms other than halogen
  • C07D333/36—Nitrogen atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
  • C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
  • C07D333/78—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems condensed with rings other than six-membered or with ring systems containing such rings

Definitions

• each of R and R is a member selected from the group consisting of H and a lower alkyl group of from 1 to 4 carbon atoms, and wherein R and R may also combine to form a member selected from the group consisting of trimethylene and pentamethylene;
• R is a member selected from the group consisting of H and a lower alkyl group of from 1 to 4 carbon atoms; and
• R is a member selected from the group consisting of H, a halogen atom, CF and a lower alkoxy group of from 1 to 4 carbon atoms, providing that R does not represent H when each of R and R is a member selected from the group consisting of H and a lower alkyl group of from 1 to 4 carbon atoms; and the pharmaceutically acceptable acid addition salts thereof, and process for preparing same.
• the compounds encompassed by the above formula exhibit pharmacological activity in narcosis potentiation, suppression of fighting behaviour and anti-convulsant activity.
• the present invention relates to novel and therapeutically valuable thieno-[2,3-e][l,4]diazepin-2-ones of the formula:
• the compounds (I) can be produced by the following methods:
• the reaction is usually carried out in a solvent such as benzene, toluene, xylene, chloroform, tetrahydrofuran, dimethylformamide or pyridine, at an elevated temperature and preferably at refluxing temperature. It is also preferred that the water formed be continuously removed azeotropically.
• a solvent such as benzene, toluene, xylene, chloroform, tetrahydrofuran, dimethylformamide or pyridine
• reaction is usually carried out in a solvent such as benzene, toluene, chloroform, tetrahydrofuran, dimethylformamide or pyridine at an elevated temperature, preferably at refluxing temperature, preferably the water or 'alkanol formed being removed continuously.
• a solvent such as benzene, toluene, chloroform, tetrahydrofuran, dimethylformamide or pyridine
• the reaction is usually carried out in a solvent first by converting a compound (1) into an alkali metal salt with a metalating agent, such as an alkali metal (Li, Na or K) or an alkali metal compound (hydride, alkoxide or amide of an alkali metal), and then reacting the alkali metal salt with compound (VI), at a temperature of from room temperature to refluxing temperature.
• a metalating agent such as an alkali metal (Li, Na or K) or an alkali metal compound (hydride, alkoxide or amide of an alkali metal
• the starting compounds (II) and (III) are new compounds and can be produced, for example, by the following methods:
• the compounds of formula (I) can be converted into the corresponding acid addition salts in a conventional manner by treatment with various inorganic and organic acids, for example, hydrochloric, hydrobromic, nitric, sulfuric, phosphoric, p-toluenesulfonic, citric, maleic, fumaric, succinic, formic, acetic and tartaric acid.
• various inorganic and organic acids for example, hydrochloric, hydrobromic, nitric, sulfuric, phosphoric, p-toluenesulfonic, citric, maleic, fumaric, succinic, formic, acetic and tartaric acid.
• the compound of formula (I) and pharmaceutically acceptable acid addition salts thereof have excellent pharmacological activities in narcosis potentiation, suppression of fighting behavior and anticonvulsant effect as shown, for example, by the following tests.
• Pentylenetetrazol 150 mg./kg. was administered subcutaneously to eight groups each consisting of 6 mice, minutes after the intraperitoneal administration of the test compound. The number of dead mice were counted within 3 hours after the administration of pentylenetetrazol, and then the ED the dose required to suppress the lethal rate to 50%, was determined graphically.
• the pharmaceutical preparations can take any conventional form such as tablets, capsules or powders.
• Formulation Example 5 mg. and 10 mg. tablets are prepared from the following compositions:
• tablet tablet tablet Compound (1) mg 5.0 10. 0 Lactose, mg 62. 3 57. 3 Corn starch, mg 25.0 25. 0 Microcrystalline cellulose, mg 6.0 6. 0 Methyl cellulose, mg 1. 0 1. 0 Magnesium stearate, mg 0. 7 0. 7
• powder powder Compound (I) percent 1.0 10. 0 Lactose, percent 88.0 79. 0 Mieroerystalline cellulose, percent 10.0 10. 0 Methyl cellulose, percent 1. 0 1. 0
• EXAMPLE 1 A solution of 7.5 g. of 2 aminoacetamido-3-benzoyl- 5,6-dihydro 4H [1]cyclopentathiophene in 50 ml. of pyridine, 1.5 g. of acetic acid and 15 ml. of benzene is refluxed for 3 hours in a flask provided with a waterremoving adaptor. The solvent is distilled off, water is added to the residue, the solution is made alkaline with sodium hydrogen carbonate and extracted with chloroform.
• the chloroform layer is dried over sodium sulfate, the chloroform is distilled off, and the crude crystals thus obtained are recrystallized from ethanol to give pale yellow crystalline 5 phenyl 1,2,7,8 tetrahydro-3H,6H [1]cyclopentathieno [2,3-e] [1,4]diazepin 2 one, melting at 243 C. with decomposition, in 73% yield.
• the oily residue is crystallized 7 from hexane to give pale yellow crystalline -o-methoxyphenyl 7 ethyl 1,2-dihydro-3H-thieno-[2,3-e] [1,41diazepin-2-one, melting at l68l69 C. (from a mixture of ethanol and hexane).
• the chloroform eluate containing the object compound is concentrated under reduced pressure, and the residue is treated with toluene to give white crystalline 5 o chlorophenyl 7 ethyl-1,2-dihydro-3H-thieno- [2,3-e][1,4]diazepin 2 one melting at 204206 C. (from a mixture of toluene and ethanol).
• EXAMPLE 5 5 p chlorophenyl 6,7 dimethyl-1,2-dihydro-3H- thieno [2,3-e][l,4]diazepin 2 one (3.0 g.) is suspended in 70 ml. of toluene. The suspension is heated to 40 C. whereupon 0.58 g. of sodium methoxide is added, and the mixture is refluxed to make a homogeneous pale brown solution. After about ml. of the methanol and toluene are distilled off, 1.3 g. of dimethyl sulfate is added slowly, and the resulting mixture is refluxed for 1 hour.
• R is a lower alkyl group of from 1 to 2 carbon atoms; R is a member selected from the group consisting of a hydrogen atom and a methyl group; and Hal represents a halogen atom; and the pharmaceutically acceptable acid addition salts thereof.
• Th compound of Claim 1 5 o chlorophenyl-7- methyl 1,2 dihydro 3H thieno [2,3-e][1,4]diazepin-2-one.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

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• 1971
  • 1971-02-11 CA CA105296A patent/CA927388A/en not_active Expired
  • 1971-02-16 DE DE2107356A patent/DE2107356C3/de not_active Expired
  • 1971-02-16 BE BE763014A patent/BE763014A/xx not_active IP Right Cessation
  • 1971-02-16 CH CH222471A patent/CH568322A5/xx not_active IP Right Cessation
  • 1971-02-16 NL NLAANVRAGE7102066,A patent/NL175723C/xx not_active IP Right Cessation
  • 1971-02-16 SE SE01973/71A patent/SE367415B/xx unknown
  • 1971-02-17 FR FR7105383A patent/FR2081520B1/fr not_active Expired
  • 1971-02-17 US US00116240A patent/US3849405A/en not_active Expired - Lifetime
  • 1971-04-19 GB GB21598/71A patent/GB1291684A/en not_active Expired

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