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WO1996004235A1 - Compose nitroalinine 4-substitue - Google Patents

Compose nitroalinine 4-substitue Download PDF

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Publication number
WO1996004235A1
WO1996004235A1 PCT/JP1995/001473 JP9501473W WO9604235A1 WO 1996004235 A1 WO1996004235 A1 WO 1996004235A1 JP 9501473 W JP9501473 W JP 9501473W WO 9604235 A1 WO9604235 A1 WO 9604235A1
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WO
WIPO (PCT)
Prior art keywords
group
compound
substituted
production
hexane
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/JP1995/001473
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English (en)
Japanese (ja)
Inventor
Shiuji Saito
Taro Matsumoto
Mariko Ohtani
Kensei Yoshikawa
Katsuo Hatayama
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Taisho Pharmaceutical Co Ltd
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Taisho Pharmaceutical Co 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 Taisho Pharmaceutical Co Ltd filed Critical Taisho Pharmaceutical Co Ltd
Priority to AU29913/95A priority Critical patent/AU2991395A/en
Publication of WO1996004235A1 publication Critical patent/WO1996004235A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
    • C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
    • C07C217/78—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C217/80—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings
    • C07C217/82—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring
    • C07C217/88—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton having amino groups and etherified hydroxy groups bound to carbon atoms of non-condensed six-membered aromatic rings of the same non-condensed six-membered aromatic ring the oxygen atom of at least one of the etherified hydroxy groups being further bound to a carbon atom of a ring other than a six-membered aromatic ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
    • C07C317/36—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atoms of the amino groups bound to hydrogen atoms or to carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/31—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
    • C07C323/33—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton having at least one of the nitrogen atoms bound to a carbon atom of the same non-condensed six-membered aromatic ring
    • C07C323/35—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton having at least one of the nitrogen atoms bound to a carbon atom of the same non-condensed six-membered aromatic ring the thio group being a sulfide group
    • C07C323/36—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton having at least one of the nitrogen atoms bound to a carbon atom of the same non-condensed six-membered aromatic ring the thio group being a sulfide group the sulfur atom of the sulfide group being further bound to an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/32—Sulfur atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/32—Sulfur atoms
    • C07D213/34—Sulfur atoms to which a second hetero atom is attached
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Definitions

  • the present invention relates to a 4-substituted ditroaniline compound useful as a pharmaceutical.
  • IL interleukin
  • IL-16 interleukin -1 and IL-16
  • IL-16 interleukin -1 and IL-16
  • antipyretic, pain and anti-inflammatory drugs autoimmune diseases such as rheumatoid arthritis and osteoporosis.
  • a 4-substituted ditroaniline compound useful as a therapeutic agent for bone diseases such as
  • NSAIDs non-steroidal anti-inflammatory drugs
  • PG brostaglandin
  • DMARD immunomodulator
  • cytokines produced by immunocompetent cells have been found.
  • IL interleukin
  • IL-6 tumor necrosis factor
  • TNF tumor necrosis factor
  • the present inventors have proposed antipyretic, analgesic, anti-inflammatory drugs, anti-inflammatory drugs such as rheumatoid arthritis, osteoporosis, etc.
  • anti-inflammatory drugs such as rheumatoid arthritis, osteoporosis, etc.
  • the present inventors have found that the following 4-substituted nitroaniline compounds can achieve the object, and have completed the present invention.
  • an object of the present invention is to provide a compound of the formula (I)
  • R ′ represents a cycloalkyl group having 5 to 8 carbon atoms
  • R 2 represents an alkyl group having 1 to 14 carbon atoms, a cycloalkyl group having 5 to 8 carbon atoms
  • X represents a group represented by one (CH 2 ) friendship-Ar (wherein, Ar represents a phenyl group, a halophenyl group, a pyridyl group or a furyl group, and n is an integer of 1 to 3).
  • Ar represents a phenyl group, a halophenyl group, a pyridyl group or a furyl group
  • n is an integer of 1 to 3
  • one 0-one NH-, one S-, one SO- or a S 0 2 - is to provide a a group represented by
  • Still another object of the present invention is to provide a pharmaceutical composition containing a 4-substituted ditroaniline compound of the formula (I) as an active ingredient.
  • Still another object of the present invention is to provide a method for inhibiting the production of inflammatory cytodynamics, which comprises administering to a human a pharmacologically effective amount of a 4-substituted nitroaniline compound of the formula (I). is there.
  • the cycloalkyl group having 5 to 8 carbon atoms of R 1 in the 4-substituted ditroaniline compound of the formula (I) is a cyclopentyl group, a cyclohexyl group, a cycloheptyl Or a cyclooctyl group.
  • the alkyl group having 1 to 14 carbon atoms of R 2 is a linear or branched alkyl group, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group , Isobutyl, n-amyl, isoamyl, ⁇ -hexyl, n-hexyl, n-octyl, n-nonanyl, n-decanyl, n-ndecanyl, n-dodecanyl, Examples thereof include an n-tridecanyl group and an n-tetradecanyl group.
  • the cycloalkyl group having 5 to 8 carbon atoms of R 2 is a cyclopentyl group, a cyclohexyl group, a cyclohexyl group or a cyclooctyl group.
  • the halophenyl group of Ar is a phenyl group in which a halogen atom such as a fluorine atom, a chlorine atom, and a bromine atom is substituted at the 2-, 3-, or 4-position of the phenyl group, and the pyridyl group is 2-, It is a 3- or 4-pyridyl group, and the furyl group is a 2- or 3-furyl group.
  • R 1 is preferably a cyclohexyl group.
  • R 2 represents an alkyl group having 1 to 14 carbon atoms, a cyclopentyl group, a cyclohexyl group, a benzyl group, a benzopentyl group, a 2-, 3- or 4-pyridylmethyl group, —, 3- or 4-pyridylpropyl or 2-furylmethyl is preferred.
  • X is over 0, One S-, one SO-, or a S 0 2 one is preferable.
  • the 4-substituted ditroaniline compound (I) of the present invention can be produced by the following method.
  • R 1 and R 2 are as defined above, Y is a fluorine atom, a chlorine atom, a bromine atom or an iodine atom, and Z is represented by 10 —, —NH— or 1 S— Group.
  • Bases used in this reaction include lithium metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; metal carbonates such as lithium carbonate, sodium carbonate, and potassium carbonate; Alkali metal bicarbonates such as sodium bicarbonate and potassium bicarbonate; Alkali metal hydrides such as sodium hydride and potassium hydride; inorganic bases such as sodium metal, metallic potassium and sodium amide Or triethylamine, diisopropylethylamine, tri-n-butylamine, 1,5-diazabicyclo [4.3.0] one 5-nonene, 1,8-diazabicyclo [5.4.0] —7-indene And organic bases such as pyridine, dimethylaminopyridine and the like.
  • Solvents used include methanol, ethanol, n-propanol, isopropanol, n-butanol , T-butanol, dioxane, tetrahydrofuran, ethyl ether, petroleum ether, n-hexane, cyclohexane, benzene, toluene, xylene, chlorobenzene, pyridine, ethyl acetate, N, N-dimethylformamide, dimethyl sulfoxide, O dichloromethane, carbon form, carbon tetrachloride, water, etc.
  • the source may be a conventional method of reducing the nitro group to an amino group, for example, ""? Radium-one-element, Raney nickel, platinum, etc. as a catalyst; iron or tin Reduction; sources using sodium sulfide-ammonium chloride; sources using sodium borohydride, lithium aluminum hydride, and the like.
  • the solvent used in this reaction may be arbitrarily selected depending on the reduction method. Generally, alcohols such as methanol, ethanol, n-propanol, isopropanol, n-butanol and t-butanol, water, acetic acid and ethyl acetate are used. , Dioxane, tetrahydrofuran, and acetonitrile.
  • the acetylation may be performed by a usual method for acetylating aniline, and examples of the acetylating agent include drunkic acid, acetyl chloride, acetyl bromide, and anhydrous anhydride.
  • the solvent used in this reaction may be the solvent used in the original reaction or ethyl ether, petroleum ether, n-hexane, cyclohexane, benzene, toluene, xy Examples include benzene, benzene, pyridine, N, N-dimethylformamide, dimethyl sulfoxide, dichloromethane, chloroform, carbon tetrachloride, water, acetic acid, and sulfuric acid.
  • the solvent to be used is preferably selected arbitrarily according to the nitrating agent, and is selected from the group consisting of acetic acid, anhydrous acid, trifluoroacetic acid, sulfuric acid, dichloromethane, chloroform, carbon tetrachloride, benzene, toluene, dioxane, and ethanol. , N-propanol, isopropanol and the like.
  • Compound (IX) can be obtained by reacting compound 1) with 2-nitroacetanilide compound (VII) in the presence of a base.
  • Compound (K) of the present invention can be obtained by continuously hydrolyzing compound (K) in the reaction system or by hydrolyzing after isolation.
  • Examples of the base used in this reaction include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, and potassium hydroxide; alkali metal carbonates such as lithium carbonate, sodium carbonate, and potassium carbonate; sodium hydrogencarbonate Metal hydrogencarbonate such as sodium hydrogencarbonate; sodium metal hydride such as sodium hydride; lithium metal hydride; inorganic base such as sodium gold, metal sodium hydride, sodium amide; or Triethylamine, diisopropylethylamine, tri-n-butylamine, 1,5-diazabicyclo [4.3.0] — 5-nonene, 1,8-diazabicyclo [5.4.0] 17-indene, pyridine And organic bases such as dimethylaminopyridine.
  • Solvents used include methanol, ethanol, n-propanol, isopropanol, n-butanol, t-butanol, dioxane, tetrahydrofuran, ethyl ether, petroleum ether, n-hexane, cyclohexane, benzene, toluene, xylene, Chlorobenzene, pyridine, ethyl ethyl sulphate, N, N-dimethylformamide, dimethyl Examples include rusulfoxide, dichloromethane, chloroform, carbon tetrachloride, and water.
  • a crown ether such as 18-crown-16 ether
  • the hydrolysis is a usual method for hydrolyzing an amide under basic or acidic conditions.
  • the basic conditions are preferable, and the base is, for example, water.
  • the base is, for example, water.
  • examples include lithium oxide, sodium hydroxide, potassium hydroxide, sodium acid, lithium carbonate, sodium methoxide, sodium ethoxide, and potassium t-butoxide.
  • the acidic condition include a method using an acid such as hydrochloric acid, hydrobromic acid, and sulfuric acid.
  • the solvent used in this reaction is preferably arbitrarily selected depending on the hydrolysis conditions.
  • examples include water, methanol, ethanol, propanol, t-butanol, tetrahydrofuran, dioxane, benzene, toluene, xylene, and benzene. , N-dimethylformamide, dimethylsulfoxide, formic acid, acetic acid and the like.
  • the compound (I b) which is a group represented by —SO a — is, for example, as shown in the following reaction formula, wherein Z of the compound (la) of the present invention obtainable by the method of the above (1) is -S It can be obtained by oxidizing the compound (la ′) which is a group represented by —.
  • Solvents used in this reaction are methanol, ethanol, n-propanol, isopropanol, dichloromethane, chloroform, carbon tetrachloride, dioxane, tetrahydrofuran, acetone, acetonitrile, ethyl acetate, ethyl ether, petroleum ether, and hexane. , Cyclohexane, benzene, toluene, xylene, benzene, pyridine, N, N-dimethylformamide, water and the like.
  • the 4-substituted ditroaline compound of the present invention thus obtained has an inhibitory effect on the production of inflammatory cytokines, and is used for autoimmune diseases such as antipyretic, analgesic, anti-inflammatory drugs, rheumatoid arthritis, and bone diseases such as osteoporosis It is useful as a therapeutic agent for.
  • the dosage of the 4 g-substituted nitroaniline compound of the present invention is although it varies depending on the age, body weight, symptoms, administration route, administration frequency, etc., it is usually 1 to 100 mg / day.
  • Production Example 20 Production example using methanol, ethanol, n-propanol, n-butanol, n-amyl alcohol, n-octanol, isoprolanol or isoaamyl alcohol in place of n-hexanol used in 20
  • the compounds of the present invention shown in Table 2 were obtained.
  • the thioether compound of the present invention obtained by the method of Production Examples 1, 2, 4 to 11, and 13 to 18 was used instead of the compound of the present invention obtained by the method of Production Example 3 used in Production Example 60. do it By oxidizing in the same manner as in Production Example 60, the compounds of the present invention shown in Table 5 (compounds of Production Examples 61 to 76) were obtained.
  • Heparin-treated normal human peripheral blood is layered under aseptic conditions on Lymphoprep (Daiichi Pharmaceutical) to remove erythrocytes.
  • the cells were suspended in RPMI-1640 medium (Gibco) supplemented with 1 OmM of buffer and 2 mM of L-glutamine, and the cell number was adjusted to 2 ⁇ 10 6 eel 1 s / m 1.
  • the value (M) was determined.
  • the concentration of test compound 1 X 1 0- 7 M, 1 X 1 0- 6 M and 1 X 1 0 - 3 concentration Oh Rui 5 M is 1 X 1 0- 5 M, 0. 33 X 1 O
  • the concentration of the test compound was adjusted to 0, and the concentration was set as 0.
  • T is IL-1J5 at each concentration of test compound or
  • the 4-substituted ditroaniline compounds of the present invention can be used as antipyretics, analgesics, anti-inflammatory drugs, anti-inflammatory drugs such as rheumatoid arthritis, osteoporosis, etc. Useful as a therapeutic agent for bone disease ⁇ 4>.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pyridine Compounds (AREA)

Abstract

L'invention concerne un composé nitroaniline 4-substitué représenté par la formule générale (I). Dans cette formule, R1 représente un C¿5?-C8 cycloalkyle, R?2¿ représente un C¿1?-C14 alkyle, un C5-C8 cycloalkyle ou -(CH2)n-Ar où Ar représente un phényle, un halophényle, un pyridyle ou un furyle et n représente un nombre entier compris entre 1 et 3, et X représente -O-, -NH-, -S-, -SO- ou -SO2-. Ces composés ont pour effet d'inhiber la production de cytokines inflammatoires et ils sont donc utiles comme antipyrétiques, analgésiques ou anti-inflammatoires. Egalement, ce sont des remèdes contre des maladies auto-immunes telles que la polyarthrite rhumatoïde et contre des maladies des os comme l'ostéoporose.
PCT/JP1995/001473 1994-08-05 1995-07-25 Compose nitroalinine 4-substitue Ceased WO1996004235A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU29913/95A AU2991395A (en) 1994-08-05 1995-07-25 4-substituted nitroaniline compound

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP6/184631 1994-08-05
JP18463194 1994-08-05

Publications (1)

Publication Number Publication Date
WO1996004235A1 true WO1996004235A1 (fr) 1996-02-15

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Application Number Title Priority Date Filing Date
PCT/JP1995/001473 Ceased WO1996004235A1 (fr) 1994-08-05 1995-07-25 Compose nitroalinine 4-substitue

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AU (1) AU2991395A (fr)
WO (1) WO1996004235A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7045519B2 (en) 1998-06-19 2006-05-16 Chiron Corporation Inhibitors of glycogen synthase kinase 3

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
WANG, SHAOYIN. YIYAO GONGYE. Vol. 17, No. 5, (1986), pages 209-213. *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7045519B2 (en) 1998-06-19 2006-05-16 Chiron Corporation Inhibitors of glycogen synthase kinase 3
US7425557B2 (en) 1998-06-19 2008-09-16 Novartis Vaccines And Diagnostics, Inc. Inhibitors of glycogen synthase kinase 3

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Publication number Publication date
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