WO1984001576A1 - Derives de pyrrolidone fondus - Google Patents

Derives de pyrrolidone fondus Download PDF

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Publication number
WO1984001576A1
WO1984001576A1 PCT/JP1982/000401 JP8200401W WO8401576A1 WO 1984001576 A1 WO1984001576 A1 WO 1984001576A1 JP 8200401 W JP8200401 W JP 8200401W WO 8401576 A1 WO8401576 A1 WO 8401576A1
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WO
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Prior art keywords
compound
acid
reaction
melting point
added
Prior art date
Application number
PCT/JP1982/000401
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English (en)
Japanese (ja)
Inventor
Kentaro Hiraga
Yoshiaki Saji
Original Assignee
Takeda Chemical Industries Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Takeda Chemical Industries Ltd filed Critical Takeda Chemical Industries Ltd
Priority to PCT/JP1982/000401 priority Critical patent/WO1984001576A1/fr
Priority to US06/478,478 priority patent/US4590189A/en
Priority to DE8383301656T priority patent/DE3378763D1/de
Priority to AT83301656T priority patent/ATE39483T1/de
Priority to EP83301656A priority patent/EP0091241B1/fr
Priority to DK136983A priority patent/DK161311C/da
Priority to JP58057228A priority patent/JPS58189163A/ja
Priority to CA000424994A priority patent/CA1196330A/fr
Priority to HU831142A priority patent/HU189679B/hu
Priority to SU833576799A priority patent/SU1382400A3/ru
Priority to KR1019830001350A priority patent/KR900007780B1/ko
Publication of WO1984001576A1 publication Critical patent/WO1984001576A1/fr
Priority to US06/832,138 priority patent/US4788191A/en
Priority to US07/241,851 priority patent/US4879293A/en
Priority to SG993/90A priority patent/SG99390G/en
Priority to HK1041/90A priority patent/HK104190A/xx

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Classifications

    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/44—Iso-indoles; Hydrogenated iso-indoles
    • C07D209/46—Iso-indoles; Hydrogenated iso-indoles with an oxygen atom in position 1
    • 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
    • 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
    • C07D417/06—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 carbon chain containing only aliphatic carbon atoms
    • 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
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • 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
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/5532—Seven-(or more) membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/572—Five-membered rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/59—Hydrogenated pyridine rings

Definitions

  • the present invention is a pharmaceutical or chromatic ⁇ new ⁇ pin ⁇ isoindolinone derived bright as an intermediate
  • benzodiazepine compounds have been commonly mourned as anxiolytics.
  • drug dependence, hypnotic mourning, muscle relaxation, and other side effects are present, and it is not necessarily satisfactory.
  • the present inventors have conducted research to develop a non-benzodiazepine compound as an anxiolytic agent, and as a result, succeeded in producing a compound having excellent armor, and completed the present invention.
  • the present invention uses the formula
  • X represents a cyclic group which may be substituted
  • ⁇ represents a carboxyl which may be esterified or amidated
  • the A ring is one or two halogens (eg CI, Br, F, I). It may be replaced.
  • Z is — (Cfi 2 ) OT —
  • m is preferably 4.
  • Z is particularly preferably 1
  • Examples of the ⁇ -like group represented by X include an aryl group (eg, phenyl, naphthyl), a heterocyclic group (eg, pyridyl, pyridazinyl, bilazinyl, pyrimidinyl, quinolyl, na: 7-tilidinole, thiazolyl) , Benzothiazolinole).
  • C 3-7 cycloalkynole group eg, cyclopentyl, cyclohexyl, cycloheptyl.
  • These groups may have 1-3 substituents, such as halogens (eg,
  • C1-4 alkyl eg, methyl, ethyl, propyl, isopropynole, butyl, isobutyl
  • C1-4 alkoxy eg, methoxy, ethoxy, propoxy
  • Isopropoxy methylenedioxy, phenoxy, benzyloxy, hydroxy, C2-5 alkanoloxy (eg, acetoxy, sspiionyloxy, butyryloxy), amino.
  • DiC1-alkynoleamino eg, dimethylamino
  • Getylamino, dipropylamino, dibutinoreamino ⁇ -hydroxy-Ci.
  • Alkinole eg, hydroxymethyl, hydroxyxetil
  • C2-5 Alkinole e.g., acetinole, propioninole, butylinole
  • benzoinole amid, nitro, cyano, trifinole I-4
  • Anolequinolequinole eg, acetinoleoxyetinole, propioninoleoxymethinole, C2-5) Alkanoylamino (eg, acetylamino, propionylamino :), anorecoxy-capable olevonyl (eg, methoxycanoleponyl, ethoxycarponyl) and the like.
  • the carboxyl group represented by Y may be esterified or amidated, and the esterified carboxyl group may have the formula
  • the amidated carboxyl group is represented by the formula
  • fl 1 is C 1-4 alkyl (eg, methyl, ethyl, propyl, isopropynole, butynole, isobutynole, tert-butynole), feninole 1 Cl-4 alkyl (eg, benzyl) ), Phenyl and the like.
  • J3 ⁇ 4 2 and R 3 may be the same or different and represent hydrogen, C 1-4 alkynole (eg, methinole, ethynole 'propinole', isopropynole), phenyl-Ci-14-anolequinole (eg, benzinole, Phenethylenol, (-methynolebenzinole), phenyl, thiazolyl, benzothiazolyl, etc., and these groups are, for example, halogens (eg, C 1, ⁇ r, F, I) doxydoxy, C 1-4 alcohol Xy (eg, methoxy, ethoxy, propoxy, isopropoxy), C25-anolecoxica canoleboninole (-, eg, methoxycanoleboninole, ethoxycanoleboninole), di-C14-anolequinoleamine ( , Dimethino
  • R 2 and 3 may form a heterocyclic group together with the adjacent N, and such a heterocyclic group is usually a 5- to 17-membered ring, and in addition to the above ⁇ , the second heteroatoms ⁇ , 0 Or it may contain S.
  • Specific examples of the heterocyclic group include lipidinole, piperidino, piperazinole, monoreholino, thiazolidinole, Hexahydrodroazepinyl and the like.
  • heterologous groups may have 1-2 substituents, such as hydroxy, C14 acrekoxy (eg, methoxy, ethoxy, propoxy, i Sopropoxy), C1-4 anolequinole (eg, methinole, etinole, propinole, isop ⁇ -pinole), C2-5anolecoxycarbonyl (eg, methoxycarbonylethoxycanoleponinole), feninole-C 1-4—Anolequinole (eg, benzinole, phenetinere, methinolebenzinele), pheninole, pyridino, pyridinole, etc.
  • the cyclic groups eg, fenilole
  • the cyclic groups are further halogen, Hydroxy, C 14 -anolequinole, C 14 -anolekoxy, trif-n-olemethyl may have any substituent.
  • the saturated hydrocarbon represented by CnH 2 n may be either straight-chain or molecular, and particularly preferably, n is 1 or 2.
  • the compound (1) of the present invention has the formula
  • (U-a) is converted to, for example, potassium carbonate, sodium hydroxide.
  • Hydrolysis in the presence of a base such as lithium or hydroxylated water yields (I-1)
  • This reaction is usually carried out in methanol, ethanol, tetrahydrofuran, dimethylformamide, or other solvents. The reaction is carried out at a temperature of ⁇ 10 to 100 ° C., usually between room temperature and the boiling point of the solvent (clear, methanol-free).
  • the compound (I -1) wherein n is 2 can be produced by the following reaction.
  • Ms represents a methanesulfonyl group, and other symbols have the same meanings as described above. That is, the compound of the general formula (VI) can be obtained by reducing (V) with, for example, hydrogen hydride. This countermeasure is at room temperature in tetrahydrofuran
  • the reaction rate may be adjusted by cooling or heating as needed. Is reacted with methanesulfonyl chloride in pyridine to give mesylate (VI, which is then reacted with lithium cyanide) to obtain a compound of the general formula (Hb). The reaction is carried out by heating and refluxing with the use of toluene or ethanol as a solvent, and the thus obtained (ff-b) is led to a compound (I-1) in which n is 2 by a hydrolysis reaction.
  • the hydrolysis reaction can be carried out under general hydrolysis conditions for nitrile groups such as ripening and reflux in concentrated hydrochloric acid.
  • a compound (I-1) in which 11 is 3 can be produced by the following reaction using the compound of the general formula (VII) as a starting material.
  • the compound of the formula is reacted with sodium iodide under heating in an organic solvent such as acetone, dimethylformamide, tetrahydrofuran or the like, and then heated to an oxalate (V, which is then converted to malonate).
  • c acid diester e.g., malonic acid dimethyl chill 'Ma o phosphate Jechiru
  • K is firstly led to (II-C) in the same manner as in the case of producing (I-l) from (V), and gives a compound ( ⁇ -1) in which n is 3 by a hydrolysis reaction.
  • R 1 has the same meaning as described above] to react with an alcohol represented by the formula ( 1 ), followed by esterification.
  • the ester (I-2) can be obtained by heating the mixture of both in the presence of a catalyst.
  • the reaction can usually be promoted by using alcohol (X) of ⁇ j and removing azeotropically the water formed by the reaction.
  • the sensitizing agent sulfuric acid, inorganic acids such as salts, para-toluenesulfonic acid, trifluoroacetic acid anhydride, trifluoromethanesulfonic anhydride or the like, or its anhydrides, soot, cobalt, iron, aluminum, etc.
  • Kum 3 ⁇ 4 Salts of heavy metals (clear, BuSnOaH, Bu 2 SnO). ( ⁇ -1) with alcohol 00
  • (I-2) there is a method in which the reaction is carried out in the presence of a dehydrating reagent such as dicyclohexane / recarposide or carbonyldimidazole.
  • a dehydrating reagent such as dicyclohexane / recarposide or carbonyldimidazole.
  • This reaction is usually carried out in pyridine. Any other organic solvents can be used as long as the markings are correct.
  • the reaction temperature was -20. C ⁇ 15 h. It is conveniently performed at room temperature, usually in the C range.
  • Examples of the reactive derivative of (I-1) include, for example, dehydration of one molecule of water from two molecules of an acid halide (eg, acid chloride, acid ⁇ -mid) or (1-1).
  • the reaction of these with alcohol (X) can usually be carried out in any solvent which does not interfere with the reaction, for example, ether, benzene, tetrahydrofuran, dichloromethane, chlorophonolem, dimethinoleformamide. You.
  • This reaction is carried out, if necessary, in the presence of any base, for example, pyridine, triethylamine, 4- dimethylaminopyridine, diisopropinoleethylamine, triethylenediamine, and the reaction temperature is -10. C-100. C, preferably 0 ° C to 30 ° C.
  • (I-2) is also an alkali metal salt of (I-1) (eg, sodium salt) or a silver salt.
  • N-hydr ⁇ -xydiacylimidoesters eg, ⁇ -Droxysuccinic acid
  • Midestenol ⁇ —hydroxyphthalenoleate, ⁇ -hydroxy-5-norbornene-2,3-dicarxymidester
  • the reaction is usually carried out in a solvent such as dichloromethane, tetrahydrofuran, chloroform, dimethylformamide, and acetonitrile, but any solvent can be used as long as the reaction is not inhibited.
  • This reaction is necessary, for example, pyridin, triethylamine, 4-dimethylaminopyridin, disopropinoleetinoreamin, triethylenediamine, carbon dioxide, sodium hydroxide. It is performed in the presence of any base.
  • the reaction temperature is usually about 10 to 100, preferably about 0 to 30. c. If (I-1) is not used as a reactive derivative, and if the person mourns as it is, for example, dihydric hexinole resin, canoleponinole resinimidazolone, ditinol cyanate, diphenyl phosphoryl azide, etc.
  • reaction can be carried out in the presence of a base such as pyridine, picolin, triethylamine, sodium hydroxide, and carbonic acid.
  • a base such as pyridine, picolin, triethylamine, sodium hydroxide, and carbonic acid.
  • the reaction temperature is usually in the range of about ⁇ 20 ° C. to 150 ° C. In most cases, the reaction proceeds sufficiently even at room temperature.
  • This reaction is carried out in an organic solvent such as toluene'ethyl methoxide or methoxetane, but any other organic solvent can be used as long as the reaction is not inhibited.
  • the reaction temperature is usually from 10 to 120.
  • ⁇ p2 R 3 [in the formula, B represents a hachigen, R 2 and R 3 have the same meanings as above]] and triphenylphosphine are obtained by a method known per se, for example, toluene, benzene, ethyl acetate, acetonitrile or dimethylformyl. 10 to 12 0 in the medium. Heating to C (Kum Salt Ph)
  • R 2 and R 3 are as defined above] by a method known per se, for example, 0 to 50 in an aqueous solution. It can be produced by applying an aqueous solution, such as sodium hydroxide, or aqueous solution, in c.
  • an aqueous solution such as sodium hydroxide, or aqueous solution
  • Methylenecarboxamide can be produced and is also useful as a synthetic intermediate for various compounds.
  • Y is a carboxyl group (I-1)
  • Y is a carboxyl group (I-1)
  • compound (I) of the present invention is basic, it can be isolated in the form of a salt with an acid.
  • OMPI Eg, hydrochloride, nitrate, phosphate, hydrobromide etc.
  • organic acids eg, acetate, fumarate 'maleate' succinate 'tartrate
  • Methanesulfonate etc.
  • the compounds of the present invention have optical isomers, and both of these isomers and racemates are naturally included in the scope of the present invention.
  • (I) is usually obtained as a racemic form, but it can be separated into two optically active forms by a conventional method of optical resolution by a dragon, and an optically active form can be obtained. Can be.
  • the compound (1) of the present invention acts on the central nervous system, and has a strong anti-anxiety effect in an anti-conflict test in rats.
  • the compound of the present invention has a minimum lethal dose (MLD) of 500 or more in mice and a minimum effective dose (MED) of 2.5 / or less in rats, has an extremely wide drug safety range, and is currently marketed as anxiolytic. Compared to the conventional benzodiazepines, it has a very weak hypnotic condolence and muscle relaxation as a side effect, and is safe and useful as an anxiolytic for humans and other mammals.
  • Target disease names include, for example, autonomic imbalance, vomiting vomiting, nervous dermatitis.
  • Ffl alopecia, angina pectoris, dyspnea, etc. can be used for the prevention or treatment of these diseases.
  • This compound also has anticonvulsant activity, and can be used, for example, in epilepsy and traumatic spasticity.
  • the compound is orally or non-orally administered to mammals including humans in various forms such as tablets, granules, capsules, injections, and suppositories.
  • the dosage varies depending on the type of disease, symptoms, etc., but is usually about 0.001 to 50 per body weight per day for animals, and 0.1 to 100 per day for adults for humans. Is 0.5 to 20.
  • the pharmacological properties of the compound (I) of the present invention were studied by measuring the ability of the radiolabeled diase'bam to displace the benzodiazepine receptor. '
  • the suspension was filtered with a whatman GF / B glass fiber filter, and the radioactivity of 3 H-diazepam on the fi Iter was measured by a liquid scintillation method.
  • the concentration of the test drug in the case where the amount of 3 H-diazepam binding was suppressed by 50% was defined as the IC go value.
  • Elemental analysis value C 21 3 ⁇ 42 N 2 0 2 Calculated value C, 75.42: H .6.63: N, 8.38 Fiber value C, 75.42: H, 6.44: N, 8.25 Example 4.
  • ester forms A) and B) obtained by the above resolution were hydrolyzed with dioxane-35 hydrochloric acid, respectively, to obtain optically active liponic acid without racemization (recrystallized from methanol).
  • ⁇ _OMPl__ (4) was added, and the mixture was compressed with a compression tablet machine to produce 100 tablets (1) having a diameter of 7 containing 1 W per tablet.
  • novel condensed pyrrolinone derivative (I) provided by the present invention has excellent pharmacological action and is useful as a pharmaceutical or the like.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Composés de formule (I) où X représente un groupe cyclique facultativement substitué, Y représente un groupe carboxyle facultativement estérifié ou amidé, Z représente -CH--CH-CH--CH-, -S-(CH2)l-S- (l : nombre entier entre 1 et 3), -N--CH-CH--N- ou -(CH2)m- (m : nombre entier entre 3 et 5), le cycle A peut être substitué par un atome halogène et n représente un nombre entier entre 1 et 3, ainsi que leurs sels. Ces composés présentent un fort effet auxiolytique chez les mammifères et sont utiles comme agents prophylactiques et de guérison pour les affections psychosomatiques, les névroses d'angoisse etc.
PCT/JP1982/000401 1982-04-02 1982-10-07 Derives de pyrrolidone fondus WO1984001576A1 (fr)

Priority Applications (15)

Application Number Priority Date Filing Date Title
PCT/JP1982/000401 WO1984001576A1 (fr) 1982-10-07 1982-10-07 Derives de pyrrolidone fondus
US06/478,478 US4590189A (en) 1982-04-02 1983-03-24 Condensed pyrrolinone derivatives, their production and use
DE8383301656T DE3378763D1 (en) 1982-04-02 1983-03-24 Condensed pyrrolinone derivatives, and their production
AT83301656T ATE39483T1 (de) 1982-04-02 1983-03-24 Kondensierte pyrrolinon-derivate, und ihre herstellung.
EP83301656A EP0091241B1 (fr) 1982-04-02 1983-03-24 Dérivés condensés de pyrrolinone, et leur préparation
DK136983A DK161311C (da) 1982-04-02 1983-03-25 Analogifremgangsmaade til fremstilling af 2-substituerede 3-karboxyalkyl-4,5-kondenserede pyrrolin-1-onderivater eller salte deraf
CA000424994A CA1196330A (fr) 1982-04-02 1983-03-31 Produits de condensation de la pyrrolinone; preparation et utilisation
JP58057228A JPS58189163A (ja) 1982-04-02 1983-03-31 縮合ピロリノン誘導体
HU831142A HU189679B (en) 1982-04-02 1983-04-01 Process for producing condensed pyrrolinone derivatives
SU833576799A SU1382400A3 (ru) 1982-10-07 1983-04-01 Способ получени конденсированных производных пирролинона или их гидрохлоридов
KR1019830001350A KR900007780B1 (ko) 1982-04-02 1983-04-01 축합된 피롤리논 유도체의 제조방법
US06/832,138 US4788191A (en) 1982-04-02 1986-04-23 1,3-dithiolano-, 1,4-dithiino- and 1,4-dithiepino[2,3-C]pyrrole derivatives, their production and use
US07/241,851 US4879293A (en) 1982-04-02 1988-09-08 Pyrrols [3,4-8]pyrazine derivatives, their production and use as anti-anxiety agents
SG993/90A SG99390G (en) 1982-04-02 1990-12-13 Condensed pyrrolinone derivatives,and their production
HK1041/90A HK104190A (en) 1982-04-02 1990-12-13 Condensed pyrrolinone derivatives,and their production

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PCT/JP1982/000401 WO1984001576A1 (fr) 1982-10-07 1982-10-07 Derives de pyrrolidone fondus

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WO (1) WO1984001576A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7064135B2 (en) 2001-10-12 2006-06-20 Novo Nordisk Inc. Substituted piperidines
US7767695B2 (en) 2001-09-14 2010-08-03 High Point Pharmaceuticals, Llc Substituted piperidines
EP2243776A1 (fr) 2001-10-12 2010-10-27 High Point Pharmaceuticals, LLC Piperidines substituées et leur utilisation dans le traitement de maladies liées au recepteur histaminique H3
KR20230081959A (ko) * 2021-11-30 2023-06-08 주식회사 베노바이오 Bet 단백질을 저해하는 신규한 카르복스아마이드 리독스 유도체 및 이를 이용한 안과질환 예방 및 치료용 조성물

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7767695B2 (en) 2001-09-14 2010-08-03 High Point Pharmaceuticals, Llc Substituted piperidines
US7064135B2 (en) 2001-10-12 2006-06-20 Novo Nordisk Inc. Substituted piperidines
EP2243776A1 (fr) 2001-10-12 2010-10-27 High Point Pharmaceuticals, LLC Piperidines substituées et leur utilisation dans le traitement de maladies liées au recepteur histaminique H3
KR20230081959A (ko) * 2021-11-30 2023-06-08 주식회사 베노바이오 Bet 단백질을 저해하는 신규한 카르복스아마이드 리독스 유도체 및 이를 이용한 안과질환 예방 및 치료용 조성물
KR102619332B1 (ko) 2021-11-30 2024-01-02 주식회사 베노바이오 Bet 단백질을 저해하는 신규한 카르복스아마이드 리독스 유도체 및 이를 이용한 안과질환 예방 및 치료용 조성물

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