CN114524827A - Pyrazole derivative for treating severe nervous disease and application thereof - Google Patents
Pyrazole derivative for treating severe nervous disease and application thereof Download PDFInfo
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- CN114524827A CN114524827A CN202210160881.8A CN202210160881A CN114524827A CN 114524827 A CN114524827 A CN 114524827A CN 202210160881 A CN202210160881 A CN 202210160881A CN 114524827 A CN114524827 A CN 114524827A
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- pharmaceutically acceptable
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 7
- 150000003217 pyrazoles Chemical class 0.000 title abstract description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 8
- 229940125782 compound 2 Drugs 0.000 claims description 4
- 229940126214 compound 3 Drugs 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 2
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- 230000000926 neurological effect Effects 0.000 claims 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 5
- 201000010099 disease Diseases 0.000 abstract description 3
- 229940079593 drug Drugs 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 10
- 108010053652 Butyrylcholinesterase Proteins 0.000 description 9
- 102100032404 Cholinesterase Human genes 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 102100033639 Acetylcholinesterase Human genes 0.000 description 6
- 108010022752 Acetylcholinesterase Proteins 0.000 description 6
- 229940022698 acetylcholinesterase Drugs 0.000 description 6
- 102000003914 Cholinesterases Human genes 0.000 description 5
- 108090000322 Cholinesterases Proteins 0.000 description 5
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 5
- 229960004373 acetylcholine Drugs 0.000 description 5
- 229940048961 cholinesterase Drugs 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 229940125904 compound 1 Drugs 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- JEXVQSWXXUJEMA-UHFFFAOYSA-N pyrazol-3-one Chemical compound O=C1C=CN=N1 JEXVQSWXXUJEMA-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000005935 Sulfuryl fluoride Substances 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- OBTWBSRJZRCYQV-UHFFFAOYSA-N sulfuryl difluoride Chemical compound FS(F)(=O)=O OBTWBSRJZRCYQV-UHFFFAOYSA-N 0.000 description 2
- 150000008053 sultones Chemical class 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- WRIUFOROJHIQRC-UHFFFAOYSA-M 2-(2-iodoacetyl)oxyethyl-trimethylazanium;iodide Chemical compound [I-].C[N+](C)(C)CCOC(=O)CI WRIUFOROJHIQRC-UHFFFAOYSA-M 0.000 description 1
- GANZODCWZFAEGN-UHFFFAOYSA-N 5-mercapto-2-nitro-benzoic acid Chemical compound OC(=O)C1=CC(S)=CC=C1[N+]([O-])=O GANZODCWZFAEGN-UHFFFAOYSA-N 0.000 description 1
- KZPWRQDQRGSYBZ-UHFFFAOYSA-M C[N+](C)(C)CCSCCCCI.[I-] Chemical compound C[N+](C)(C)CCSCCCCI.[I-] KZPWRQDQRGSYBZ-UHFFFAOYSA-M 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 241001262617 Japonica Species 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 description 1
- 229910018503 SF6 Inorganic materials 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000007131 anti Alzheimer effect Effects 0.000 description 1
- -1 arylsulfonyl fluoride Chemical compound 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 229960003530 donepezil Drugs 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 229960003980 galantamine Drugs 0.000 description 1
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 150000002611 lead compounds Chemical class 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960004136 rivastigmine Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- SFZCNBIFKDRMGX-UHFFFAOYSA-N sulfur hexafluoride Chemical group FS(F)(F)(F)(F)F SFZCNBIFKDRMGX-UHFFFAOYSA-N 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D497/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms
- C07D497/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D497/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention relates to a pyrazole derivative with severe nervous disease treatment effect, which has good treatment and rehabilitation effects on Alzheimer disease and other diseases, and shows substantial scientific progress and prominent beneficial effects compared with the existing medicines.
Description
Technical Field
The invention relates to the field of medicinal chemistry, in particular to a pyrazole derivative with a severe nervous disease treatment effect, and also relates to a preparation method, a medicinal composition and application of the derivative.
Background
Alzheimer's Disease (AD) is a neurologically severe condition that occurs in the elderly or pre-senile stages, is a progressive degenerative disease of the nervous system, has a progressive deterioration in memory and other cognitive disorders, and affects about 4700 million people worldwide.
The most effective strategy to ameliorate the symptoms of the disease is to restore the levels of acetylcholine (ACh) using cholinesterase (ChE), known as acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. To date, the only five AD drugs have been approved by the FDA, four of which are ChE inhibitors, of which rivastigmine, galantamine and donepezil have been used clinically. ChE is one of the most valuable and major targets for the discovery of new anti-AD agents.
Butyrylcholinesterase (BuChE) exists in mammals besides AChE, and researches show that the butyrylcholinesterase is also involved in the metabolic process of acetylcholine and plays an important role in regulating the level of ACh, so that BuChE is considered as a potential therapeutic target by researchers in recent years.
Since the introduction of the term "sultone" by Erdmann in 1888 to describe the lactone of hydroxysulfonic acids, the sultone moiety has gradually been used as a structural scaffold in pharmaceutical chemistry and exhibits excellent biological and pharmacological activities, such as anti-HIV-I and HIV-II, anti-human cytomegalovirus, anti-butyrylcholinesterase, anti-carbonic anhydrase. Heterocyclic structures are also widely used as sulfoalkylating agents for the synthesis of complex natural drugs.
The invention uses arylsulfonyl fluoride and pyrazolone to prepare a novel sultone-fused pyrazole skeleton with cholinesterase inhibitory activity by a sulfur (VI) fluoride exchange chemical method, which is not reported in the prior art.
Disclosure of Invention
The technical problem to be solved by the invention is as follows:
in a first aspect of the present invention, there is provided a compound represented by formula 1, or a pharmaceutically acceptable salt thereof, having the structure:
preferably, the pharmaceutically acceptable salt is selected from: hydrochloride, hydrobromide, phosphate, sulfate, acetate, oxalate, tartrate;
in another aspect of the present invention, there is provided a method for preparing a compound represented by formula 1, which comprises the following steps:
and reacting the compound 2 with the compound 3 under the action of DBU to obtain a compound 1.
The specific reaction steps are as follows:
to a solution in a dry reaction tube (20mL) were added sulfuryl fluoride compound 3(0.5mmol) and pyrazolone compound 2(0.5mmol, 1.0 equiv.), DBU (36mg dissolved in 10mL CH2Cl2, 2mL, 5-30 mol%) and an inorganic base (0.5mmol, 1.0 equiv.). The resulting mixture was stirred at room temperature for 8-12 hours, monitored by TLC. The product was purified by silica gel column chromatography (petroleum ether/dichloromethane ═ 7: 1).
Preferably, the inorganic bases are each independently selected from at least one of potassium carbonate, sodium bicarbonate, potassium bicarbonate.
Another aspect of the present invention provides a pharmaceutical composition, which comprises a compound represented by formula 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.
The invention also relates to application of the compound shown in the formula 1 or the pharmaceutically acceptable salt thereof or the pharmaceutical composition containing the compound in preparing a medicament for treating or preventing severe neurological diseases; preferably, the neurologic critical condition is alzheimer's disease.
Compared with the prior art, the invention has the beneficial effects that:
(1) the invention provides a new pyrazole derivative with the effect of treating severe nerve diseases, widens the range of the prior art, and can be continuously optimized as a lead compound;
(2) the compound shown in the formula 1 shows good therapeutic activity in pharmacological tests, and can be used for preventing and treating Alzheimer disease.
Detailed Description
The present invention is described in more detail below to facilitate an understanding of the present invention. The compounds of the present invention may be prepared by a number of methods well known to those skilled in the art of synthesis. The compounds of formula 1 may be prepared using the reactions and techniques outlined below, together with methods known in the art of synthetic organic chemistry or variations thereof as understood by those skilled in the art. Preferred methods include, but are not limited to, those described below. The reaction is carried out in a solvent suitable for the reagents and materials used and for the conversion to be effected. Furthermore, in the synthetic methods described below, it is to be understood that all proposed reaction conditions (including choice of solvent, reaction atmosphere, reaction temperature, experimental duration and work-up procedures) are selected as standard conditions for the reaction, which should be readily ascertained by one skilled in the art of organic synthesis. Not all compounds falling within a given class may be compatible with certain reaction conditions required in certain of the described methods. These limitations on substituents compatible with reaction conditions will be apparent to those skilled in the art and alternative methods may be used.
Example 1: synthesis of Compound 1
To a solution in a dry reaction tube (20mL) were added sulfuryl fluoride compound 3(0.5mmol) and pyrazolone compound 2(0.5mmol, 1.0 equiv.), DBU (36mg in 10mL CH2Cl2 to form a solution, 3mL) and NaHCO3(42mg, 0.5mmol, 1.0 equiv.). The resulting mixture was stirred at room temperature for 8-12 hours, monitored by TLC. The product was purified by silica gel column chromatography (petroleum ether/dichloromethane ═ 7: 1). The reaction yield was 54% and the HPLC purity was 99.8%.
The molecular formula is as follows: c11H10N2O4S；ESI-MS：267.19[M+H]+
1H NMR(400MHz，CDCl3)：δ2.78-2.97(m，4H)，3.42(m，2H)，6.43-6.51(m，2H)，7.39(s，1H)，8.23(s，1H)。
Example 2: acetylcholinesterase/butyrylcholinesterase activity assay experiment of Compound represented by formula 1
The Anguillar Japonica AChE (C3389-500 UN; Sigma) and horse serum BuChE (C4290-1 KU; Sigma) were measured according to the method of Ellman. Both enzymes as well as the substrate and DTNB colour developer were purchased directly from Sigma and used directly. The experiment was performed in 48 well plates, 100. mu.L of 0.036U/mL EeAChE or eqBuChE and 100. mu.L of 0.1M (pH 8) phosphate buffer were added to each well, 100. mu.L of the compound at various concentrations was added and after incubation at 37 ℃ for 20 minutes, 100. mu.L of 0.35mM iodoacetylcholine iodide (ACh; A5751-1G; Sigma) or 0.5mM iodobutylthiocholine iodide (BuCh; 20820-1G; Sigma) and 100. mu.L of 0.35mM 5,5' -dithiobis-2-nitrobenzoic acid (DTNB; D8130-1G; Sigma) were added in a final volume of 500. mu.L. The choline esterase combined with the substrate and acted with DTNB to generate yellow anion 5-thio-2-nitrobenzoic acid, the developer is incubated for 20 minutes continuously, the absorbance change is measured at 410nm by an enzyme-linked immunosorbent assay, and the IC50 value is determined graphically by an inhibition curve (logarithmic inhibitor concentration to inhibition percentage).
The results show that compound 1 has no inhibitory activity on AChE and an IC50 value of 0.18 ± 0.02 μ M for BuChE. As can be seen, the compound 1 of the present invention may be a potential therapeutic drug for Alzheimer's disease.
The foregoing describes preferred embodiments of the present invention, but is not intended to limit the invention thereto. Modifications and variations of the embodiments disclosed herein may be made by those skilled in the art without departing from the scope and spirit of the invention.
Claims (6)
1. A compound of formula 1, or a pharmaceutically acceptable salt thereof, having the structure:
2. a compound of formula 1 according to claim 1, or a pharmaceutically acceptable salt thereof, selected from: hydrochloride, hydrobromide, phosphate, sulfate, acetate, oxalate, tartrate.
3. A process for preparing a compound of formula 1 according to claim 1, which comprises the following reaction scheme:
and reacting the compound 2 with the compound 3 under the action of DBU to obtain a compound 1.
4. A pharmaceutical composition comprising a compound represented by formula 1 or a pharmaceutically acceptable salt thereof as set forth in any one of claims 1-2, and a pharmaceutically acceptable carrier.
5. Use of a compound represented by formula 1 or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 2 or a pharmaceutical composition according to claim 4 for the preparation of a medicament for treating or preventing severe neurological conditions.
6. The use of claim 5, wherein the neurological condition is Alzheimer's disease.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210160881.8A CN114524827A (en) | 2022-02-22 | 2022-02-22 | Pyrazole derivative for treating severe nervous disease and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210160881.8A CN114524827A (en) | 2022-02-22 | 2022-02-22 | Pyrazole derivative for treating severe nervous disease and application thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114524827A true CN114524827A (en) | 2022-05-24 |
Family
ID=81625662
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210160881.8A Pending CN114524827A (en) | 2022-02-22 | 2022-02-22 | Pyrazole derivative for treating severe nervous disease and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114524827A (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN88103735A (en) * | 1987-06-17 | 1988-12-28 | 三井东压化学株式会社 | It is the medicine of active ingredient treatment cerebrovascular disease that new pyrazoline derivative reaches with this compound |
| US20070142362A1 (en) * | 2005-12-20 | 2007-06-21 | Solvay Pharmaceuticals B.V. | 4,5-Dihydro-(1H)-pyrazole derivatives as cannabinoid CB1 receptor modulators |
| CN102695710A (en) * | 2009-11-13 | 2012-09-26 | 默克雪兰诺有限公司 | Tricyclic pyrazol amine derivatives |
| US20200129488A1 (en) * | 2017-06-01 | 2020-04-30 | Eisai R&D Management Co., Ltd. | Dementia therapeutic agent combining pyrazoloquinoline derivative and memantine |
| WO2021089781A1 (en) * | 2019-11-07 | 2021-05-14 | Inflazome Limited | Treatment or prevention of psychiatric brain disorders using the nlrp3 inhibitor n-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1 -isopropyl-1 h-pyrazole-3-sulfonamide |
-
2022
- 2022-02-22 CN CN202210160881.8A patent/CN114524827A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN88103735A (en) * | 1987-06-17 | 1988-12-28 | 三井东压化学株式会社 | It is the medicine of active ingredient treatment cerebrovascular disease that new pyrazoline derivative reaches with this compound |
| US20070142362A1 (en) * | 2005-12-20 | 2007-06-21 | Solvay Pharmaceuticals B.V. | 4,5-Dihydro-(1H)-pyrazole derivatives as cannabinoid CB1 receptor modulators |
| CN102695710A (en) * | 2009-11-13 | 2012-09-26 | 默克雪兰诺有限公司 | Tricyclic pyrazol amine derivatives |
| US20200129488A1 (en) * | 2017-06-01 | 2020-04-30 | Eisai R&D Management Co., Ltd. | Dementia therapeutic agent combining pyrazoloquinoline derivative and memantine |
| WO2021089781A1 (en) * | 2019-11-07 | 2021-05-14 | Inflazome Limited | Treatment or prevention of psychiatric brain disorders using the nlrp3 inhibitor n-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1 -isopropyl-1 h-pyrazole-3-sulfonamide |
Non-Patent Citations (1)
| Title |
|---|
| 程勇等: "阿尔茨海默病的药物治疗", 《中国临床药理学杂志》, vol. 15, no. 4, pages 295 - 298 * |
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