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WO2007119984A1 - Composé dérivé de l'acide salicylique et composition pharmaceutique le contenant - Google Patents

Composé dérivé de l'acide salicylique et composition pharmaceutique le contenant Download PDF

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Publication number
WO2007119984A1
WO2007119984A1 PCT/KR2007/001815 KR2007001815W WO2007119984A1 WO 2007119984 A1 WO2007119984 A1 WO 2007119984A1 KR 2007001815 W KR2007001815 W KR 2007001815W WO 2007119984 A1 WO2007119984 A1 WO 2007119984A1
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WO
WIPO (PCT)
Prior art keywords
ethylamino
disease
benzoic acid
compound
hydroxy
Prior art date
Application number
PCT/KR2007/001815
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English (en)
Inventor
Byoung-Joo Gwag
Sung-Ig Cho
Jae-Young Cho
Young-Ae Lee
Han-Yeol Byun
Sun-Mi Park
Sun-Young Ko
Moon-Jung Lee
Jin-Hee Shin
Jae-Keun Lee
Jin-Hwan Lee
Bok-Seon Yoon
Chun-San An
Keun-Sil Ryu
Hyang-Ran Lim
Original Assignee
Neurotech 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 Neurotech Co., Ltd. filed Critical Neurotech Co., Ltd.
Publication of WO2007119984A1 publication Critical patent/WO2007119984A1/fr

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C227/14—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton from compounds containing already amino and carboxyl groups or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/52—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
    • C07C229/54—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C229/64—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton with amino and carboxyl groups bound to carbon atoms of the same non-condensed six-membered aromatic ring the carbon skeleton being further substituted by singly-bound oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C223/00—Compounds containing amino and —CHO groups bound to the same carbon skeleton
    • C07C223/06—Compounds containing amino and —CHO groups bound to the same carbon skeleton having amino groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • 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
    • C07C323/24—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 atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/25—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 atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated

Definitions

  • the present invention relates to new salicylic acid derivative compounds having specific chemical formula, pharmaceutical composition containing the same and treating or preventing method using the same.
  • Glutamate is an excitatory neurotransmitter mediating slow excitatory synaptic transmission through N-methyl-D-aspartate (NMDA) receptors and fast excitatory synaptic transmission through alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic (AMPA) receptors.
  • NMDA glutamate receptors play an important role in learning and memory, and plasticity of nervous system [Siegel G. J. et al . , Basic Neurochemistry, 6 th edition, Lippincott Williams & Wilkins : 315-333 (1999) ].
  • excess activation of NMDA glutamate receptors can cause neuronal death [Olney, J. W. and Sharpe, L.
  • Reactive oxygen is known to be one of main reasons for the cerebral nervous disease and ocular diseases. Reactive oxygen
  • Parkinson's disease Parkinson's disease (Prasad et al., J. Am. Coll. Nutr. 18, 413-423 (1999)), etc.; ocular diseases like glaucoma (Neufeld et al., J. Glaucoma. 11, 221-225 (2002)), diabetic retinopathy (Chung et al., Arzneistoffforschung. 55, 573-580 (2005)), macular degeneration (Richer et al., Optometry. 75,
  • anti-oxidants like vitamin E or acetyl-L- carnitine are evaluated not to be effective in Alzheimer's
  • Inflammation is reactions of blood membrane and cell against injury factor originated from injured cell and foreign material entered into body.
  • Main purpose of inflammation reaction is to remove extraneous material and injured cell (or cell tissue) , but inflammation reaction can be a cause of chronic diseases like rheumarthritis, pancreatitis, gastritis, colitis and arteriosclerosis.
  • Non-steroid anti-inflammatory drugs drugs suppressing activity of cyclooxygenase taking part in production of prostaglandin, have been developed and widely used to alleviate symptoms, including pain, of inflammatory diseases, but there are side effects to block the use of the NSAIDs.
  • gastrointestinal disorders such as dyspepsia, gastritis, ulcer, bleeding and perforation are side effects often happening after administration of NSAIDs.
  • Celecoxib and Rofecoxib, selective COX-2 (cyclooxygenase-2 ) enzyme inhibitors having low side effects on gastrointestinal damage have been developed and used for treating arthritis and pain.
  • the object of the present invention is to provide a new compound useful for treating or preventing brain
  • the object of the present invention is to provide a therapeutic agent having treating efficacy for brain disease, ocular disease, pain and inflammatory disease and no side effect, that is, a therapeutic agent suppressing excitatory toxicity, having no gastric damage unlike known anti-inflammatory drug, showing cell protective effect in low concentration, and showing anti-oxidant effect.
  • the present invention is to provide a salicylic acid derivative compound represented by the below chemical formula 1 or its pharmaceutically acceptable salt: [Chemical formula 1]
  • X is O or S;
  • R 1 is hydrogen or alkyl;
  • R 2 is hydrogen, alkyl or alkanoyl;
  • R 3 is hydrogen or alkyl;
  • R 4 is phenyl, biphenyl or naphthyl which is unsubstituted or substituted with one or more selected from the group consisting of halogen, haloalkyl, alkyl, alkoxy, haloalkoxy and nitro; and n is an integer from 2 to 4.
  • the present inventors have prepared and evaluated a lot of compounds, and succeeded in inventing the fact that the salicylic acid derivative compound or its pharmaceutically acceptable salt is useful for treating or preventing cerebral nervous disease, ocular disease, pain and inflammatory disease.
  • the present invention is to provide a salicylic acid derivative compound represented by the below chemical formula 1 or its pharmaceutically acceptable salt.
  • alkyl is Ci-C 5 alkyl, and more preferably C 1 -C 3 alkyl.
  • Alkyl described above includes, but is not limited to, methyl, ethyl, propyl, isopropyl, butyl, sec-butyl and tert-butyl .
  • Alkoxy preferably, is Ci-C 5 alkoxy, and more preferably Ci-C 3 alkoxy.
  • Alkoxy described above includes, but is not limited to, methoxy, ethoxy, and propanoxy.
  • Halogen includes, but is not limited to, fluoride, chloride, bromide, and iodide.
  • alkanoyl is C 2 -Ci 0 alkanoyl, and more preferably C 3 -C 5 alkanoyl.
  • Alkanoyl described above includes, but is not limited to, ethanoyl, propanoyl, and cyclohexanecarbonyl .
  • base addition salts of the compound of the present invention can be made by reacting the free base of the compound with enough amount of desirable base and adequate inert solvent.
  • Pharmaceutically acceptable base addition salt includes, but is not limited to, sodium, potassium, calcium, ammonium, magnesium or salt made by organic amino.
  • acid addition salts of the compound of the present invention is basic, acid addition salts of the compound
  • Pharmaceutically acceptable acid addition salt includes, but is not limited to, propionic acid, isobutylic acid, oxalic acid, malic acid, malonic acid, benzoic acid, succinic acid, suberic acid, fumaric acid, mandelic acid, phthalic acid, benzenesulfonic acid, p-tolylsulfonic acid, citric acid, tartaric acid, methanesulfonic acid, hydrochloric acid, bromic acid, nitric acid, carbonic acid, monohydrogencarbonic, phosphoric acid, monohydrogen-phosphoric acid, dihydrogen- phosphoric acid, sulfuric acid, monohydrogen-sulfuric acid, hydrogen iodide, and phosphorous acid.
  • the pharmaceutically acceptable salt of the present invention includes, but is not limited to, a salt of amino acid like arginate and an analog of organic acid like glucuronic or galactunoric.
  • Some of the compounds of the present invention may be hydrated form, and may exist as solvated or unsolvated form. A part of compounds according to the present invention exist as crystal form or amorphous form, and any physical form is included in the scope of the present invention.
  • some compounds of the present invention may contain one or more asymmetric carbon atoms or double bond, and therefore exists in two or more stereoisomeric forms like racemate, enantiomer, diastereomer, geometric isomer, etc. The present invention includes these individual stereoisomers of the compounds of the present invention.
  • the present invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising the salicylic acid derivative compound represented by the above chemical formula 1 or its
  • compositions comprising: pharmaceutically acceptable salt; and pharmaceutically acceptable excipient or additive.
  • the compound or its pharmaceutically acceptable salt of the present invention may be administered alone or with any convenient carrier, diluent, etc.
  • the pharmaceutical composition of the present invention may be formulated in a solid or liquid form.
  • the solid formulation includes, but is not limited to, a powder, a granule, a tablet, a capsule, a suppository, etc.
  • the solid formulation may further include, but is not limited to, a diluent, a flavoring agent, a binder, a preservative, a disintegrating agent, a lubricant, a filler, etc.
  • formulation includes, but is not limited to, a solution such as water solution and propylene glycol solution, a suspension, an emulsion, etc., and may be prepared by adding suitable additives such as a coloring agent, a flavoring agent, a stabilizer, a thickener, etc.
  • a powder can be made by simply mixing the
  • a granule can be prepared as follows: mixing the compound or its pharmaceutically acceptable salt, a pharmaceutically acceptable diluent and a pharmaceutically acceptable binder such as polyvinylpyrrolidone, hydroxypropylcellulose, etc; and wet-granulating with adequate solvent like water, ethanol, isopropanol, etc, or direct- compressing with compressing power.
  • a tablet can be prepared as follows: mixing the compound or its pharmaceutically acceptable salt, a pharmaceutically acceptable diluent and a pharmaceutically acceptable binder such as polyvinylpyrrolidone, hydroxypropylcellulose, etc; and wet-granulating with adequate solvent like water, ethanol, isopropanol, etc, or direct- compressing with compressing power.
  • a tablet can be prepared as follows: mixing the compound or its pharmaceutically acceptable salt, a pharmaceutically acceptable diluent and a pharmaceutically acceptable binder such as polyvinylpyrrolidone, hydroxypropylcellulose, etc; and wet-
  • composition of the present invention may be administered in forms of, but not limited to, oral formulation, injectable formulation (for example, intramuscular,
  • composition of the present invention may be formulated in a suitable dosage unit comprising a pharmaceutically acceptable and non-toxic carrier, additive and/or vehicle, which all are generally used in the art, depending on the routes to be administered. Depot type of a pharmaceutically acceptable and non-toxic carrier, additive and/or vehicle, which all are generally used in the art, depending on the routes to be administered. Depot type of a pharmaceutically acceptable and non-toxic carrier, additive and/or vehicle, which all are generally used in the art, depending on the routes to be administered. Depot type of
  • the present invention also provides a use of the salicylic acid derivative compound or its pharmaceutically acceptable salt for treating and/or preventing brain disease, ocular disease, pain and inflammatory disease. That is, the present invention provides a pharmaceutical composition for treating or preventing brain disease, ocular disease, pain and inflammatory disease, comprising the salicylic acid derivative compound represented by the above chemical formula 1 or its pharmaceutically acceptable salt.
  • the salicylic acid derivative compound or its pharmaceutically acceptable salt can be used for treating or preventing degenerative brain diseases such as Alzheimer's disease, Parkinson's disease, Lou Gehrig's disease, Huntington' s disease; cerebrovascular diseases such as stroke; acute brain or spinal cord injury; ocular disease such as glaucoma, macular degeneration and diabetic retinopathy; inflammatory disease such as arteriosclerosis, gastritis, colitis, arthritis, nephritis, hepatitis, degenerative disease; and pain.
  • degenerative brain diseases such as Alzheimer's disease, Parkinson's disease, Lou Gehrig's disease, Huntington' s disease
  • cerebrovascular diseases such as stroke
  • acute brain or spinal cord injury ocular disease such as glaucoma, macular degeneration and diabetic retinopathy
  • inflammatory disease such as arteriosclerosis, gastritis, colitis, arthritis, nephritis, hepatitis, degenerative disease; and pain.
  • the compound of the present invention may be administered daily at a dose of approximately 0.01 mg/kg to approximately 100 g/kg, preferably approximately 0.1 mg/kg to approximately 10 g/kg.
  • the dosage may be varied according to the patient's conditions (age, sex, body weight, etc.), the severity of patients in need thereof, the used effective components, diets, etc.
  • the compound of the present invention may be administered once a day or several times a day in divided doses, if necessary.
  • the present invention provides a method of preparing the salicylic acid derivative compound represented by the above chemical formula 1.
  • the salicylic acid derivative compounds can be prepared by reacting the compound of the below chemical formula 2 with the compound of the below chemical formula 3. ⁇ Chemical formula 2>
  • reaction scheme 1 HOOC ⁇ MeOOC ⁇ Me0QC
  • reaction conditions of the reaction scheme 1 are as follows: (a) MeOH, H 2 SO 4 , reflux, 6 hours; (b) DIBOC, NaHCO 3 , THF/H 2 O, room temperature, 7 hours; (c) acetyl chloride, DMF, K 2 CO 3 , room temperature, 6 hours; (d) 1,4-dioxane (4N-HC1) , room temperature, 8 hours.
  • the reaction conditions of the reaction scheme 1 are not limited to these conditions . More specifically, the salicylic acid derivative compound of the chemical formula 1 can be prepared, but is not limited to, by the below reaction scheme 2. ⁇ Reaction scheme 2>
  • reaction conditions of the reaction are described.
  • the reaction conditions of the reaction are described.
  • scheme 2 are as follows: (a) DCC, MC, room temperature, 2 hours; (b) acetic acid, NaBH 4 , 1,4-dioxane, reflux, 20 minutes; (c) CH 3 I, DMF, K 2 CO 3 , 40, 6 hours; (d) acetic acid, HC1/H 2 O, reflux, 12 hours.
  • the reaction conditions of the reaction scheme 2 are not limited to these conditions.
  • Figure 1 is anti-inflammatory activity results of the compound 11 (100 uM) , one example of the compounds according to the present invention, using BV-2 cell line.
  • FIG. 1 is an efficacy evaluation result of compound 11 using arthritis animal model induced by collagen. After injection of collagen, compound 11 (25mg/kg/day) and methotrexate (MTX, control, lmg/kg/week) were intraperitoneally injected. After that, gross examination was performed for 4 weeks, and results were evaluated as arthritis index.
  • Figure 3 is efficacy evaluation results of compound 11 using arthritis animal model induced by collagen. After injection of collagen, compound 11 (25mg/kg/day) and methotrexate (MTX, control, lmg/kg/week) were intraperitoneally injected. After that, gross examination was performed for 4 weeks, and results were evaluated as arthritis index.
  • Figure 3 is efficacy evaluation results of compound 11 using arthritis animal model induced by collagen. After injection of collagen, compound 11 (25mg/kg/day) and methotrexate (MTX, control, lmg/kg/week) were intraperitoneally injected. After that, gross examination was performed for 4 weeks, and results were evaluated
  • Example 1 by using 2-acetoxy-5-aminobenzoic acid methyl ether (1.03 g, 5.07 mmole) , 4-fluorophenoxypropionic acid (1.02 g, 5.57 mmole) and DCC (1.14 g, 5.55 mmole), 1.38 g (72.3 % yield) of 2-acetoxy-5- [3- (4-fluorophenoxy) propionylamino] benzoic acid methyl ether was obtained as a white solid.
  • reaction mixture was slowly warmed up to 0 ° C over 30 minutes and quenched by slow (over 1 hour) addition of N 1 N- diisopropylethylamine (140 mL, 0.8 mol).
  • N 1 N- diisopropylethylamine 140 mL, 0.8 mol
  • Cortical cell cultures (DIV 11 - 15) were exposed to 100 uM NMDA for 10 minutes to induce neuronal death by excitotoxicity, alone or with inclusion of 10 - 1000 uM of compounds 2, 3, 7, 11 or 17. Neuronal death was analyzed 24 hours later by measuring levels of LDH released into the bathing medium, and IC 50 value were calculated. Results were shown in the below table 16 (NMDA toxicity) . In result, compound 2, 3 and 11 showed relatively high IC 50 value, and tested compounds completely blocked neuronal death by excitotoxicity induced by
  • BV2/RAW 297.6 cell line was treated with LPS with inclusion of 10 uM, 30 uM or 100 uM of the present compound. After 24 hours of
  • IC 50 value of each compound was calculated and shown in the below table 16 (NO suppression) .
  • IC 50 values of compound 11, 21 and 22 were 17.17 uM, 11.4 uM, and 16.3 uM, respectively.
  • the salicylic acid derivative compound of the present invention is thought to be useful as anti-inflammatory agent because the compound suppresses the activity of NO intervening inflammation reaction.
  • CHO cell lines were incubated without any treatment or incubated after be treated with 20 uM, 60 uM or 100 uM of the compound of the present invention. After 24 hours of incubation, 50 ul of culture medium was reacted with ELISA kit provided by BioSource. Then, the absorbance was evaluated with ELISA reader at 540 nm, and IC 50 values of each compound were calculated. Results were shown in the below table 16 (A ⁇ suppression) .
  • IC 50 of compound 8 was 22.9 uM
  • IC 50 of compound 11 was 50.67 uM.
  • BV2 microglia cell line was treated with both 100 uM of lipopolysaccharide (LPS) , inflammation-inducing material of bacteria toxin, and 100 uM of the compound 11 of the present invention, together, and
  • collagen-induced arthritis model rheumarthritis animal model
  • Bovine type II collagen was mixed with complete Freund's adjuvant to make an emulsion, and the emulsion was intradermally injected into the origin site of 8 ⁇ 10 week-old DBA/lLacJ mouse tail.
  • Intradermal boosting was performed by the same method 2 weeks later. 25 mg/kg/day of compound 11, 1 mg/kg/week of methotrexate (comparative example) or 10% vehicle (control) was intraperitoneally injected one week after the second intradermal injection of collagen. For 2 ⁇ 3
  • Stroke is a disease caused by blood circulation disorders (thrombosis, embolism or stenosis) . Blood circulation disorders induce neuronal death.
  • glutamate an excitatory neurotransmitter, accumulates at the synaptic cleft of neuronal cell, and over-activation of Ca 2+ -peameable glutamate receptor rapidly causes the death of neuronal cell.
  • antagonist of NMDA receptor is known to significantly reduce the death of brain cell caused by hypoxic ischemia which takes part in 80% of stroke. After stroke occurs, mitochondrial electron
  • AD Alzheimer's disease
  • Alzheimer's disease is the most common form of adult onset
  • Alzheimer's disease is characterized as the presence of the neurofibrillary tangles, amyloid plaques and severe neuronal death. Recently, there are lots of literatures showing that neuronal death occurring in Alzheimer's disease is related with oxidative stress. Firstly, brain metal radical (Fe, Al, and Hg) , capable of stimulating free radical generation, secondly, lipid peroxidation, and thirdly, oxidation of protein and DNA are increased in AD. Also, NMDA receptor antagonist, memantine, has been shown to improve learning and memory in several pharmacological models of AD, and thus this memantine is sold as a therapeutic agent for treating dementia. This fact shows that excitatory toxicity is related with dementia. Therefore, the compound of the present invention having anti- oxidant effect and excitatory toxicity-suppressing effect can be
  • Parkinson's disease the degenerative nervous system disease, is characterized clinically by tremor, rigidity, bradykinesia, postural instability, akinesia, etc. and diagnosed pathologically by a selective death of dopaminergic neurons in
  • oxidative stress has been proved as a main mechanism of neuronal cell death, and lipid peroxidation, DNA oxidation, and the increases of protein carbonyl and nitrotyrosine were observed in nigra.
  • Administration of anti-oxidant is reported to have cell-
  • Lou Gehrig Disease is named amyotrophic lateral sclerosis or motor neuron disease, and the progressive degeneration of motorneurons is the pathological hallmark of this disease. Many hypothesis have been put forward to account for the selective death of motorneurons in ALS. Firstly, excitatory toxicity is
  • ALS patients have the reduced level of glutamate-transporting protein present in neuroglia cell.
  • Administration of agonist of ionic glutamate receptor into mouse spinal cord is reported to show similar pathological changes with ALS patients.
  • SOD-I gene mutation has given a hint about importance of oxidative toxicity in genetic ALS.
  • the increases of protein carbonyl groups and nitrotyrosine, the markers of oxidative toxicity are reported in brain of ALS patients. Therefore, the compound of the present invention having anti-oxidant effect and excitatory toxicity-suppressing effect can be effectively used for treating ALS.
  • present invention having anti-oxidant effect and excitatory toxicity-suppressing effect can be effectively used for treating or preventing HD.
  • Excitatory neuron toxicities are closely related to the degeneration of brain cells following traumatic brain injury (TBI) and traumatic spinal cord injury (TSCI). It has been reported that NMDA receptor antagonists decrease the neuronal death following TBI and TSCI. Oxidative toxicity and cell apoptosis are closely related with degeneration of brain cells following TBI and TSCI. Brain and spinal cord injuries cause paraparesis and quadriplegia, and show neuronal death even in distal site from injured site. However, a therapeutic agent or method for these diseases has not been developed. Influx of Ca 2+ , collapse of cell membrane, and lipid peroxidation by oxidative toxicity were observed in TBI and TSCI, and recently evidence is disclosed that cell death is related with secondary damage.
  • the increased intraocular pressure blocks blood flow into retina, causes retinal ischemia, and induces excessive release of glutamate, neurotransmitter, into synaptic cleft. Once released, glutamate induces excitotoxicity .
  • glutamate induces excitotoxicity .
  • the evidence about apoptosis caused by ischemia is accumulating. It is reported that reactive oxygen produced during re-perfusion of blood causes death of retina neuron.
  • cell necrosis inhibitor inhibits death of optic neuron in animal model of glaucoma.
  • pancreatitis is an inflammatory disease related with pancreas autodigestion caused by reflux of digestive enzyme of
  • pancreatic juice or bile of cholelithiasis into pancreas pancreatitis shows various symptoms like from mild edema to severe bleeding, which cause several damages to pancreas.
  • pancreatitis is related with inflammation, and it is reported that COX inhibitor has a protective effect in pancreatitis model and suppresses the
  • compound of the present invention can be effectively used for treating pancreatitis.
  • the present invention provides the salicylic acid derivative compound represented by the chemical formula 1 or its pharmaceutically acceptable salt having suppressing effect on excitatory toxicity, anti-oxidant effect, cell-protecting effect and anti-inflammatory effect, a pharmaceutical composition containing the compound or its salt, and a treating or preventing method using the compound or its salt.
  • composition of the present invention is useful for treating or preventing degenerative cerebral nerve disease such as amyotrophic lateral sclerosis, Parkinson's disease, Huntington' s disease, Alzheimer's disease, which are related with death of brain neuronal cell; convulsive disease such as epilepsy; stroke; trauma; brain injury caused by hydrocephalus; ocular disease such as glaucoma, diabetic retinopathy; pain disease such as neuropathic pain; and inflammatory disease such
  • arteriosclerosis as arteriosclerosis, gastritis, colitis, arthritis, nephritis, hepatitis, cancer and degenerative disease.

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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)

Abstract

La présente invention concerne un composé dérivé de l'acide salicylique ou un sel pharmaceutiquement acceptable de celui-ci utilisé pour traiter différents troubles, une composition pharmaceutique contenant ce composé ou ce sel, et un procédé de traitement ou de prévention employant ce composé ou ce sel. Le composé dérivé de l'acide salicylique de l'invention a un effet de suppression sur la toxicité excitatoire, un effet anti-oxydant, un effet de protection cellulaire, un effet anti-inflammatoire etc. et peut être utilisé efficacement pour traiter ou prévenir un trouble neuro-cérébral tel que la sclérose latérale amyotrophique, la maladie de Parkinson, la maladie de Huntington, la maladie d'Alzheimer, l'apoplexie, la lésion cérébrale traumatique et la lésion traumatique de la moelle épinière, un trouble oculaire telle que le glaucome, la rétinopathie diabétique et la dégénérescence maculaire, une douleur cérébrale telle que la douleur neuropathique, et un trouble inflammatoire tel que l'artériosclérose, la gastrite, la colite, l'arthrite, la néphrite, l'hépatite, le cancer et un trouble de dégénérescence.
PCT/KR2007/001815 2006-04-13 2007-04-13 Composé dérivé de l'acide salicylique et composition pharmaceutique le contenant WO2007119984A1 (fr)

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CN108546245A (zh) * 2018-05-22 2018-09-18 绍兴文理学院 一种抗增殖活性中间体ml-098的制备方法
US11389498B2 (en) 2016-09-21 2022-07-19 Korea Atomic Energy Research Institute Anti-inflammatory composition and composition for treatment of inflammatory disease, both comprising composite plant extract

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KR101970099B1 (ko) * 2018-02-07 2019-04-17 한국과학기술연구원 척수 손상의 예방 및 치료용 조성물

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EP0796861A1 (fr) * 1996-03-22 1997-09-24 L'oreal Nouveaux dérivés siliciés de l'acide salicilique à propriétés desquamantes
WO1999062510A2 (fr) * 1998-06-01 1999-12-09 Angiotech Pharmaceuticals, Inc. Compositions renfermant des agents anti-microtubules pour le traitement ou la prevention de maladies inflammatoires
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US11389498B2 (en) 2016-09-21 2022-07-19 Korea Atomic Energy Research Institute Anti-inflammatory composition and composition for treatment of inflammatory disease, both comprising composite plant extract
CN108546245A (zh) * 2018-05-22 2018-09-18 绍兴文理学院 一种抗增殖活性中间体ml-098的制备方法

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