Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
  • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
  • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
  • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
  • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links

Definitions

• the invention relates to N-substituted cyclic amines, their preparation and medicaments containing them.
• the invention relates to the new compounds of the
• X is an oxygen atom, a sulfur atom or one
• 1-4 carbon atoms means A stands for ethylene, trimethylene or tetramethylene, which, if X represents a group NR o , is optionally monosubstituted. by alkyl with 1-4 carbon atoms, phenyl or phenyl mono- or identically or differently disubstituted by alkyl with 1-4 carbon atoms, alkoxy with 1-4 carbon atoms or halogen with an atomic number from 9 to 35,
• R 1 is hydrogen, alkyl of 1-4 carbon atoms or alkenyl of 3-5 carbon atoms. means, where the double bond is not in the ⁇ -position to the nitrogen atom to which R 1 is bonded,
• R 2 stands for hydrogen or alkyl with 1-4 carbon atoms
• R 3 and R 4 independently of one another hydrogen, alkyl with 1-4 carbon atoms, alkoxy with 1-4 carbon atoms, alkylthio with 1-4 carbon atoms or halogen with an atomic number from 9 to Are 35 and either m is the number 0 and n is the number 1 or 2 or m and n are both the number 1, with the proviso that if X is a group NR, A is unsubstituted, m is the number 0 and n is the number 1, then R 1 is not hydrogen.
• X preferably denotes a sulfur atom or a residue NR o , in particular a sulfur atom.
• A preferably represents ethylene.
• A is preferably unsubstituted. If it is substituted, it is preferably substituted by alkyl. If it is substituted by phenyl, it is preferably substituted by unsubstituted phenyl. If phenyl is substituted, it is preferably monosubstituted. The substituent is preferably in the para position. If phenyl is disubstituted, those are
• Substituents are preferably identical. If phenyl is disubstituted, the substituents are preferably in the meta, para position. If phenyl is substituted, it is preferably substituted by halogen.
• R 1 is preferably hydrogen. If not. Means hydrogen, it is preferably alkyl. If it is alkyl with more than 2 carbon atoms, it is preferably straight-chain.
• R 2 preferably means
• R 2 can be attached to any methylene residue of the nitrogen containing ring.
• R 2 is preferably bonded to a methylene radical which is not adjacent to the ring nitrogen atom.
• R 3 and / or R 2 are preferably hydrogen. If they are not hydrogen, they are preferably attached at a position on the phenyl ring which is adjacent to the linked nitrogen-containing ring.
• R 3 and / or R 4 are not hydrogen, they are preferably alkyl, alkoxy or halogen, in particular alkyl or halogen. If both of them are not hydrogen, they are preferably identical, m is preferably the number 0.
• n is preferably the number 1.
• Alkyl and / or alkoxy and / or alkylthio preferably contain 1 or 2, in particular 1 carbon atom (s).
• Halogen preferably means chlorine or bromine, in particular chlorine.
• Alkenyl preferably contains 3 carbon atoms.
• a group of compounds of the formula I consists of the compounds of the formula Ipa,
• R o R 2 , R 3 and R 4 have the above meaning
• a a stands for ethylene, trimethylene or tetramethylene
• Alkyl with 1-4 carbon atoms or alkenyl with 3-5 carbon atoms means that the double bond is not in the ⁇ -position to the nitrogen atom to which the rest is attached.
• Another group of compounds of the formula I consists of the compounds of the formula Ipb,
• Another group of compounds of the formula I consists of the compounds of the formula Ipc,
• a a and R 1 to R 4 have the above meaning and X pc represents an oxygen atom or a sulfur atom.
• Another group of compounds of the formula I consists of the compounds of the formula Ipd,
• R o and R 1 to R 4 have the above meaning and
• Another group of compounds of the formula I consists of the compounds of the formula Ipe,
• a a and R 1 to R 4 have the above meaning and X pe represents an oxygen atom or a sulfur atom.
• Another group of compounds of the formula I consists of the compounds of the formula Ipf,
• a b , R o and R 1 to R 4 have the above meaning.
• Another group of compounds of the formula I consists of the compounds of the formula Ipg,
• a a and R 1 to R 4 have the above meaning and
• X pg represents an oxygen atom or a sulfur atom.
• the compounds of the formula I are obtained by corresponding compounds of the formula II,
• R 1 to R 4 , m and n have the above meaning and either X 'represents an oxygen atom or a sulfur atom, X''is a leaving group and
• R 0 ' is hydrogen, or X' together with a hydrogen atom represents a leaving group
• X means "a group NR" and one of R o 'and R o "is hydrogen and the other is hydrogen or alkyl of 1-4 carbon atoms, with the proviso that if X" is a group NR o ",
• A is unsubstituted, m is the number 0 and n is the number 1, then R 1 is not hydrogen, cyclizes.
• reaction according to the invention can be carried out analogously to known methods for the cyclization of analog amino derivatives.
• the reaction is preferably carried out in an inert solvent, such as methanol or ethanol, or, if the compound of the formula VI used (see below) is liquid at the reaction temperature, optionally in the absence of an additional one Solvent.
• the reaction is preferably carried out in the presence of a mineral acid such as hydrochloric acid or hydroiodic acid.
• the temperature can vary from about room temperature to about 150 ° C, it is preferably at least 50 ° C, for example, one works at the reflux temperature of the reaction mixture.
• X 'represents an oxygen atom the process is preferably carried out in water, if X' represents a sulfur atom, preferably in an organic solvent such as ether.
• the temperature can vary from about room temperature to about 100 ° C. If X 'represents a sulfur atom, it is preferred to work at room temperature.
• X' means, for example, a group NR a , in which R a represents alkyl with 1-4 carbon atoms, in particular methyl, or hydrogen.
• X ′′ is a leaving group, it is, for example, halogen or a group R b -SO 2 -O-, where R b is phenyl tolyl or lower alkyl, in particular chlorine or bromine.
• the compounds of the formula I can be isolated and purified from the reaction mixture analogously to known methods.
• the compounds of the formula I can be in free form as a base or in acid addition salt form.
• Acid addition salts e.g. the hydrochloride or hydrogen fumarate or maleate, and vice versa.
• the compounds of the formula I can also be in tautomeric form, ie in the form in which the double bond with the other nitrogen atom or with the radical X, insofar as this other nitrogen atom or this radical X is not fully substituted.
• tautomeric forms also fall within the scope of Formula I.
• the starting products can be prepared analogously to known methods.
• R 1 to R 4 , A a , m and n are as defined above,
• X a ' represents an oxygen atom or a sulfur atom
• X a ′′ denotes a leaving group, is obtained, for example, by reacting corresponding compounds of the formula III, with corresponding compounds of the formula IV,
• a solvent such as ether, e.g. at a temperature of about 0 ° to about 50 ° C, preferably at room temperature.
• X a '' is identical to X '' if the latter group is one
• a b , R 1 to R 4 , m and n have the above meaning
• R 1 Means hydrogen or alkyl having 1-4 carbon atoms, with the proviso that if A b is unsubstituted, m is 0 and n is 1, then R 1 is not hydrogen, for example by reacting corresponding compounds of Formula V,
• radical S-Y is a leaving group, where S is an i-sulfur atom, with corresponding compounds of the formula VI,
• radical X b ' is identical to the radical X' if the latter together with a hydrogen atom represents a leaving group.
• Y means, for example, alkyl with 1-4 carbon atoms, preferably methyl.
• reaction conditions for the preparation of compounds of the formula Ila in particular if X a 'represents a sulfur atom, and of compounds of the formula IIb, can be selected so that they are identical to the reaction conditions for the cyclization according to the invention.
• the compounds of the formula III or V are then reacted directly with the compounds of the formula IV or VI to give the corresponding compounds of the formula I, without intermediate isolation of the corresponding compounds of the formula Ila or Ilb.
• the 1- (2-chloroethyl) -3- (2,3-dihydro-1H-indol-1-yl) urea obtained as described below is slurried in 30 parts of water and heated to boiling for 30 minutes. The aqueous solution is concentrated with. Ammonia solution made alkaline and extracted with ethyl acetate. Evaporation of the ethyl acetate solution dried over magnesium sulfate gives the title compound (mp. Of the hydrogen maleate 125-127 ° - methanol / ethyl acetate). The starting product is obtained as follows.
• the compounds of formula I in free form or in the form of salts are distinguished by interesting pharmacodynamic properties. They can be used as a remedy.
• the compounds can be used as vasoconstrictors, e.g. for the prophylaxis and treatment of vascular headaches, such as migraines, or of orthostatic disorders, such as orthostatic hypotension and its symptoms, such as dizziness.
• Suitable dosage forms for oral applications for example, generally contain about 0.0005 to 0.5 mg in addition to solid or liquid carriers or diluents.
• Example 1 The compound of Example 1 is preferred.
• the invention also relates to medicaments which contain a compound of the formula I in free form or in the form of a physiologically tolerable acid addition salt.
• a physiologically tolerable acid addition salt for example a solution or a tablet, can be prepared according to known methods, using the usual auxiliaries and carriers.
• the compounds of the formula I or their physiologically tolerable salts can be administered as medicinal products on their own or in suitable pharmaceutical forms.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Applications Claiming Priority (8)

Publications (1)

Family

ID=27561142

Family Applications (1)

Country Status (10)

Families Citing this family (2)

Citations (5)

• 1979
  • 1979-10-02 WO PCT/CH1979/000126 patent/WO1980000840A1/de not_active Ceased
  • 1979-10-03 DE DE19792939998 patent/DE2939998A1/de not_active Withdrawn
  • 1979-10-03 DK DK415479A patent/DK415479A/da unknown
  • 1979-10-03 FI FI793063A patent/FI793063A7/fi not_active Application Discontinuation
  • 1979-10-05 GB GB7934713A patent/GB2031427A/en not_active Withdrawn
  • 1979-10-09 NL NL7907458A patent/NL7907458A/nl not_active Application Discontinuation
  • 1979-10-10 AU AU51655/79A patent/AU5165579A/en not_active Abandoned
  • 1979-10-10 PT PT70299A patent/PT70299A/pt unknown
  • 1979-10-10 FR FR7925201A patent/FR2438656A1/fr not_active Withdrawn
  • 1979-10-10 IL IL58429A patent/IL58429A0/xx unknown

Patent Citations (5)

Also Published As

Similar Documents

Legal Events