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WO2016190616A1 - Composé benzoxazole ou benzothiazole, préparation de ce dernier, et son utilisation - Google Patents

Composé benzoxazole ou benzothiazole, préparation de ce dernier, et son utilisation Download PDF

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Publication number
WO2016190616A1
WO2016190616A1 PCT/KR2016/005347 KR2016005347W WO2016190616A1 WO 2016190616 A1 WO2016190616 A1 WO 2016190616A1 KR 2016005347 W KR2016005347 W KR 2016005347W WO 2016190616 A1 WO2016190616 A1 WO 2016190616A1
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WIPO (PCT)
Prior art keywords
group
indol
thiazole
benzo
unsubstituted
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Ceased
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English (en)
Korean (ko)
Inventor
추현아
이창준
박기덕
금교창
민선준
박혜리
조서영
김지연
조선미
남민호
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Korea Institute of Science and Technology KIST
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Korea Institute of Science and Technology KIST
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Publication of WO2016190616A1 publication Critical patent/WO2016190616A1/fr
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Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A61K31/423—Oxazoles condensed with carbocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/428—Thiazoles condensed with carbocyclic rings
    • 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
    • C07D209/04—Indoles; Hydrogenated indoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C07D417/04—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 directly linked by a ring-member-to-ring-member bond

Definitions

  • Alzheimer's disease usually cause memory, cognitive and behavioral disorders.
  • Alzheimer's disease is a chronic disease that causes severe mental distress and significant medical expenses for the patient as well as the surrounding family. It is causing problems such as spending.
  • the therapeutic agents developed to date only temporarily alleviate the symptoms, and there is an urgent need for the development of drugs that fundamentally cure the disease or inhibit progression.
  • MAO Monoamine oxidase
  • MAO-A and MAO-B There is.
  • Degenerative diseases caused by Alzheimer's and Parkinson's disease are caused by oxidative stress by hydrogen peroxide due to increased MAO activity, and MAO-B inhibitors reduce oxygen radical formation and increase the amount of useful monoamines in the brain.
  • MAO-B inhibitors reduce oxygen radical formation and increase the amount of useful monoamines in the brain.
  • MAO-B inhibitors act as inhibitors of GABA production by astrocytes and restore neuronal signal transduction and brain function.
  • Irreversible MAO inhibitors such as selegiline
  • tyramine which is a substrate of MAO-B in foods when eating foods such as cheese.
  • Benzooxazole or benzothiazole compounds, isomers, derivatives thereof, or pharmaceutically acceptable salts thereof are provided.
  • a pharmaceutical composition for preventing or treating degenerative brain disease including a benzoxazole or a benzothiazole compound, an isomer, a derivative thereof, or a pharmaceutically acceptable salt thereof.
  • One aspect provides a compound represented by Formula 1, an isomer, derivative thereof, or a pharmaceutically acceptable salt thereof:
  • X may be O or S.
  • R 1 may be a halogen group.
  • R 1 can be F, Cl, or Br.
  • isomer refers to a compound having the same molecular formula but not the same way of connection or spatial arrangement of the constituent atoms in the bonsai. Isomers include, for example, structural isomers, and stereoisomers.
  • derivative refers to a compound obtained by substituting a part of the structure of the compound with another atom or group of atoms.
  • salts refers to inorganic and organic acid addition salts of compounds. Acid addition salts can be obtained from inorganic acids or nontoxic organic acids. Inorganic acids are, for example, hydrochloric acid, nitric acid, phosphoric acid, sulfuric acid, hydrobromic acid, hydroiodic acid, nitrous acid and phosphorous acid.
  • Non-toxic organic acids are, for example, oxalic acid, maleic acid, fumaric acid, malic acid, tartaric acid, citric acid, benzoic acid, aliphatic mono and dicarboxylates, phenyl-substituted alkanoates, hydroxy alkanoates and alkanedioates, aromatic acids , Aliphatic and aromatic sulfonic acids.
  • salts are, for example, sulfates, pyrosulfates, bisulfates, sulfites, bisulfites, nitrates, phosphates, monohydrogen phosphates, dihydrogen phosphates, metaphosphates, pyrophosphate chlorides, bromide , Iodide, fluoride, acetate, propionate, decanoate, caprylate, acrylate, formate, isobutylate, caprate, heptanoate, propiolate, oxalate, malonate, succinate , Suverate, sebacate, fumarate, malate, butyne-1,4-dioate, hexane-1,6-dioate, benzoate, chlorobenzoate, methyl benzoate, dinitro benzoate, hydroxy benzo Ate, methoxy benzoate, phthalate, terephthalate, benzene sulfonate, tolu
  • Another aspect provides the method of preparing a compound represented by Formula 1, an isomer thereof, a derivative thereof, or a pharmaceutically acceptable salt thereof by the method of Scheme 1 or 2 below.
  • R 1 may be a halogen group.
  • Another aspect provides a pharmaceutical composition for preventing or treating degenerative brain disease, including a compound represented by Formula 1, an isomer thereof, a derivative thereof, or a pharmaceutically acceptable salt thereof.
  • the degenerative brain disease refers to a brain disease issued with age.
  • the degenerative brain diseases include, for example, Alzheimer's disease, mild cognitive impairment, stroke and vascular dementia, prefrontal lobe dementia, Lewy body dementia, Creutzfeldt-Jakob disease, traumatic head injury, syphilis, acquired immunodeficiency syndrome and other viral infections, brain Abscesses, brain tumors, multiple sclerosis, dementia caused by metabolic diseases, hypoxia, Parkinson's disease, Lou Gehrig's disease, Huntington's disease, Pick disease, Amyotrophic lateral sclerosis, epilepsy, ischemia, stroke, attention deficit-hyperactivity disorder, schizophrenia, depression, mood swings , Post traumatic stress disorder, spinal cord injury and myelitis, or a combination thereof.
  • prevention refers to any action that inhibits or delays the onset of a disease by administration of a composition.
  • treatment refers to any action by which administration of a composition improves or advantageously alters the condition of a disease.
  • the compound represented by Formula 1, an isomer thereof, a derivative thereof, or a pharmaceutically acceptable salt thereof may be a monoamine oxidase (MAO) inhibitor.
  • MAO monoamine oxidase
  • the monoamine oxidase refers to an enzyme that makes aldehydes by oxidatively deaminoating amines such as adrenaline, dopamine, serotonin, and the like.
  • MAO binds to the coenzyme flavin adenine dinonucleotide (FAD), which is present in the mitochondrial outer membrane and present in biological tissues.
  • FAD coenzyme flavin adenine dinonucleotide
  • Subtypes of MAO include MAO-A consisting of 527 amino acid residues and MAO-B consisting of 520 amino acid residues.
  • the MAO may be MAO-B.
  • the inhibition may be inhibition of biosynthesis of MAO or inhibition of MAO activity.
  • Inhibition of MAO activity may be reversible inhibition or irreversible inhibition.
  • Inhibition of MAO activity may be selective inhibition or non-selective inhibition.
  • the compound represented by Formula 1, an isomer, derivative thereof, or a pharmaceutically acceptable salt thereof may reversibly and selectively inhibit MAO activity.
  • the pharmaceutical composition has a compound, isomers, derivatives, and pharmaceutically acceptable salts represented by the formula (1) about 0.0001% to about 10% by weight, about 0.001% to about 1% by weight, based on the total weight of the total composition, Or about 0.01% to about 0.1% by weight.
  • each component may be mixed at a ratio of about 0.0001% to about 10%, about 0.001% to about 1%, or about 0.01% to about 0.1% by weight.
  • the sum of each component is from about 0.0001% to about 10%, from about 0.001% to about 1%, or from about 0.01% to about 0.1% by weight May be included.
  • the pharmaceutical composition may further include a known active ingredient having activity for preventing or treating degenerative brain disease.
  • the pharmaceutical composition may further comprise a carrier, excipient or diluent.
  • Carriers, excipients and diluents are, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, algitates, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil.
  • compositions may each be formulated in the form of powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, or the like, external preparations, suppositories, or sterile injectable solutions according to conventional methods.
  • diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, etc. which are commonly used.
  • the solid preparation for oral administration may be a tablet, pill, powder, granule, or capsule.
  • the pharmaceutical composition may further comprise a carrier, excipient, or diluent.
  • Carriers, excipients, or diluents are, for example, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, Microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, or mineral oil.
  • the solid preparation may further comprise a lubricant such as magnesium stearate, or talc.
  • the liquid formulation for oral may be a suspension, a solution, an emulsion, or a syrup.
  • the liquid formulation may comprise water, or liquid paraffin.
  • the liquid formulation may include excipients such as wetting agents, sweetening agents, fragrances, or preservatives.
  • the preparation for parenteral administration may be sterile aqueous solution, non-aqueous solvent, suspension, emulsion, lyophilized or suppository.
  • Non-aqueous solvents or suspending agents may contain vegetable oils or esters.
  • the vegetable oil can be, for example, propylene glycol, polyethylene glycol, or olive oil.
  • the ester can be for example ethyloleate.
  • the base of the suppository may be witepsol, macrogol, tween 61, cacao butter, laurin butter, or glycerogelatin.
  • the dosage of the pharmaceutical composition depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration, and the duration, and may be appropriately selected by those skilled in the art.
  • the compound represented by Formula 1, an isomer, derivative thereof, or pharmaceutically acceptable salt thereof may be, for example, about 0.0001 mg / kg body weight to about 100 mg / kg body weight, or about 0.001 mg / kg body weight to about The amount of 10 mg / kg body weight may be administered once to several times daily.
  • the pharmaceutical composition may be administered to mammals such as humans, dogs, cats, goats, pigs, mice, rabbits, hamsters, rats, or guinea pigs by various routes.
  • the method of administration may be, for example, oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
  • Another aspect provides a method for preventing or treating degenerative brain disease, comprising administering to a subject a compound represented by Formula 1, an isomer, derivative thereof, or a pharmaceutically acceptable salt thereof.
  • the method comprises administering to a subject a compound represented by Formula 1, an isomer, derivative thereof, or a pharmaceutically acceptable salt thereof.
  • the subject may be a mammal, including a human, dog, cat, goat, pig, mouse, rabbit, hamster, rat, or guinea pig.
  • the administration depends on the condition and weight of the patient, the extent of the disease, the form of the drug, the route of administration, and the duration, but may be appropriately selected by those skilled in the art. For example, about 0.0001 mg / kg body weight to about 100 mg / kg body weight, about 0.001 mg / kg body weight to about 10 mg / body weight of the compound represented by Formula 1, an isomer, derivative thereof, or pharmaceutically acceptable salt thereof kg, about 0.01 mg / kg body weight to about 1 mg / kg body weight, or about 0.1 mg / kg body weight to about 1 mg / kg body weight may be administered once to several times daily.
  • the method of administration may be, for example, oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or intracerebroventricular injection.
  • benzoxazole or benzothiazole compound isomers, derivatives, pharmaceutically acceptable salts, preparations and uses thereof, reversible inhibition of MAO prevents or treats degenerative brain diseases efficiently and with fewer side effects. Can be.
  • Figure 1a shows the ignition probability of teeth and granule neurons according to the electrical stimulation intensity in normal mice ( ⁇ ) and APP / PS1 mice ( ⁇ )
  • Figure 1b is a water administration group ( ⁇ ), seregulin 1 week administration group ( ⁇ ) Shows the ignition probability of granulocytes in the 2 week administration group ( ⁇ ), the 2 week administration group ( ⁇ ), and the 2 weeks administration group of Compound 2 ( ⁇ )
  • FIG. It is a graph which shows the ignition probability of the water administration group, the seregiline administration group, and the compound 2 administration group ((circle)) in a normal group or an APP / PS1 mouse
  • FIG. 1D is a water administration group ( ⁇ ), a saffinamide administration group ( ⁇ ), or a formula It is a graph showing the ignition probability of teeth and granule neurons according to the electrical stimulation intensity in APP / PS1 mice administered the compound of 2.
  • FIG. 2A is an image of dopamine-secreting neurons detected by immunohistochemistry
  • FIG. 2B is an optical density of tyrosine hydroxyase measured in the normal group, the MPTP group, the sericillin group, and the compound 2 group (arbitrary unit: AU ) (**: P ⁇ 0.01, ***: P ⁇ 0.001).
  • each reaction mixture was 200 ⁇ l and each reaction mixture contained 0.01 ⁇ M to 100 ⁇ M of compounds 1-16, benzylamine-hydrochloric acid, and 1% DMSO.
  • the potential effect of the sample on hMAO-B activity was determined by the amount of hydrogen peroxide produced from benzylamine by the enzyme using the Amplex® Red MAO Assay Kit (Invitrogen).
  • the hMAO-B enzyme produces hydrogen peroxide from benzylamine, and horseradish peroxidase produces fluorescent resorufins from Amplex® Red reagent and hydrogen peroxide.
  • the absorbance of 570 nm was measured at 37 ° C. using a multi detection microplate fluorescence reader (TECAN) or flexstation. As a negative control, the reaction was carried out using no samples (compounds 1 to 16, or reference inhibitors).
  • the specific absorbance was calculated by subtracting the measured absorbance value from the background absorbance value, i.e. the absorbance value measured in the reactant containing sodium phosphate buffer instead of the hMAO-B enzyme. From the calculated specific absorbance, 50% inhibitory concentration (IC 50 ) (nM) for the MAO-B enzymes of Compounds 1-16 was calculated, and the results are shown in Table 1 below.
  • compounds 1, 2, and 16 showed excellent inhibitory activity against the MAO-B enzyme. Thus, it was confirmed that Compounds 1, 2, and 16 can treat degenerative brain diseases such as Alzheimer's by reversibly inhibiting the MAO-B enzyme.
  • Example 2 it was confirmed whether Compound 2, which was confirmed to have excellent MAO-B inhibitory activity, had an effect of preventing or treating Alzheimer's disease in vivo.
  • APP / PS1 mice (Jack-son Laboratory B6C3-Tg (APPswe, PSEN1dE9), stock no.004462) were prepared. Compound 2 was mixed with water the mice drink and the mice were orally administered for 2 weeks at a dose of 10 mg / kg / day. On the other hand, only water was administered to normal mice or APP / PS1 mice as a negative control, and 10 mg / kg / day of selegiline (Sigma-Aldrich) or 10 mg / kg / day sapine to APP / PS1 mice as a positive control. Safinamide (Sigma-Aldrich) was administered.
  • the spike probability was measured by electrophysiological methods in brain tissue sections of mice.
  • the electrical stimulation with a frequency of 0.1 Hz, a vibration time of 100 ⁇ s, and a current of 100 to 1000 ⁇ A was applied to the dental gyrus of the cerebral hippocampus 10 times, and the number of spike firing reactions of the granule cells was measured.
  • Counting ignition probability was calculated.
  • the experiment was repeated while varying the intensity of the electrical stimulus to measure the probability of ignition according to the intensity of the stimulus.
  • the measured ignition probabilities are shown in FIGS. 1A-1D.
  • APP / PS1 mice suffering from Alzheimer's disease had a significantly reduced probability of firing granule neurons compared to normal mice.
  • the APP / PS1 mice administered seregiline for 4 weeks compared to the APP / PS1 mice administered seregiline for 2 weeks, the probability of ignition is reduced, the longer the administration period The therapeutic efficacy of Alzheimer's disease has decreased.
  • APP / PS1 mice that received Compound 2 for 2 weeks had an increased probability of ignition at lower stimuli than mice that received seregulin for 2 weeks.
  • the ignition probability of the APP / PS1 mice administered Compound 2 in the electrical stimulation of 200 ⁇ A stimulation intensity increased about 70% compared to the ignition probability of APP / PS1 mice administered the seregiline, It increased about 30% more than the ignition probability of normal mice.
  • APP / PS1 mice administered Compound 2 for 2 weeks increased the probability of ignition at low stimulation compared to APP / PS1 mice administered sapinamide for 2 weeks.
  • Compound 2 was able to prevent or treat Alzheimer's disease by enabling normal neuronal signal transmission in Alzheimer's disease, compared to seregulin, an irreversible inhibitor of MAO-B, or sapinamide, a reversible inhibitor of MAO-B. .
  • mice were intraperitoneally administered 1-methyl-4-phenyl-1,2,3,6-tetrapidypyridine (MPTP) at a dose of 20 mg / kg.
  • MPTP 1-methyl-4-phenyl-1,2,3,6-tetrapidypyridine
  • Compound 2 or sericillin was administered orally at a dose of 10 mg / kg / day for a total of 3 days from the day before the administration of MPTP to the day after the administration.
  • Mice were sacrificed on day 7 from the day of MPTP administration and the brains of mice were harvested.
  • Dopamine-releasing neurons in the striatum and substantia nigra pars compacta of the extracted brain were measured by immunohistochemistry.
  • tyrosine hydroxylase a marker of dopamine secreting neurons
  • a rabbit anti-TH antibody Pel-freez cat. No. p40101-0
  • the striatum and dendritic TH of TH decreased in Parkinson's model mice treated with MPTP, while the amount of TH in the selegiline and Compound 2 groups recovered similarly to that of the normal group.
  • TH was recovered statistically significantly in the compound 2 administration group in the striatum.
  • the recovery of TH by Compound 2 was found to increase dopamine production and to improve the symptoms of Parkinson's disease, which is manifested by decreased dopamine secretion.

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  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne un composé selon un aspect de l'invention, ou un isomère, un dérivé ou un sel pharmaceutiquement acceptable de ce dernier ; une préparation de ces derniers ; et une utilisation de ces derniers. Ces composés peuvent efficacement prévenir ou traiter des maladies cérébrales dégénératives en produisant moins d'effets secondaires, en inhibant de manière réversible la MAO.
PCT/KR2016/005347 2015-05-22 2016-05-20 Composé benzoxazole ou benzothiazole, préparation de ce dernier, et son utilisation Ceased WO2016190616A1 (fr)

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KR10-2015-0071732 2015-05-22
KR1020150071732A KR101709731B1 (ko) 2015-05-22 2015-05-22 벤조옥사졸 또는 벤조티아졸 화합물, 그의 제조, 및 용도

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110240604A (zh) * 2019-07-08 2019-09-17 荆楚理工学院 一种吡啶并噁唑衍生物的合成方法

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007035405A2 (fr) * 2005-09-16 2007-03-29 University Of Pittsburgh Methode in vivo ou in vitro de detection de depots d'amyloides presentant au moins une proteine amyloidogene
WO2007149030A1 (fr) * 2006-06-19 2007-12-27 Astrazeneca Ab Nouveaux benzoxazoles substitués par hétéroaryle
WO2009155017A2 (fr) * 2008-05-30 2009-12-23 Merck & Co., Inc. Nouveaux azabenzoxazoles substitués
WO2011052888A2 (fr) * 2009-10-29 2011-05-05 (주)퓨쳐켐 Dérivés aryliques fonctionnalisés par (3-fluoro-2-hydroxy)propyle ou leurs sels pharmaceutiquement acceptables, leur procédé de préparation et composition pharmaceutique les contenant comme principes actifs pour le diagnostic ou le traitement de maladies cérébrales neurodégénératives
KR20130020949A (ko) * 2011-08-18 2013-03-04 한국과학기술연구원 퇴행성 뇌질환의 예방 또는 치료용 약학적 조성물 및 이의 스크리닝 방법

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2007035405A2 (fr) * 2005-09-16 2007-03-29 University Of Pittsburgh Methode in vivo ou in vitro de detection de depots d'amyloides presentant au moins une proteine amyloidogene
WO2007149030A1 (fr) * 2006-06-19 2007-12-27 Astrazeneca Ab Nouveaux benzoxazoles substitués par hétéroaryle
WO2009155017A2 (fr) * 2008-05-30 2009-12-23 Merck & Co., Inc. Nouveaux azabenzoxazoles substitués
WO2011052888A2 (fr) * 2009-10-29 2011-05-05 (주)퓨쳐켐 Dérivés aryliques fonctionnalisés par (3-fluoro-2-hydroxy)propyle ou leurs sels pharmaceutiquement acceptables, leur procédé de préparation et composition pharmaceutique les contenant comme principes actifs pour le diagnostic ou le traitement de maladies cérébrales neurodégénératives
KR20130020949A (ko) * 2011-08-18 2013-03-04 한국과학기술연구원 퇴행성 뇌질환의 예방 또는 치료용 약학적 조성물 및 이의 스크리닝 방법

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110240604A (zh) * 2019-07-08 2019-09-17 荆楚理工学院 一种吡啶并噁唑衍生物的合成方法
CN110240604B (zh) * 2019-07-08 2021-04-16 荆楚理工学院 一种吡啶并噁唑衍生物的合成方法

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