Heterocyclic compound, preparation method therefor and use thereof

A technology of heterocyclic compounds and heterocyclic groups, which is applied in the application field of preparing medicines for diseases of the central nervous system, and can solve problems such as side effects

Inactive Publication Date: 2015-09-09
SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, pure D 2 Antagonist or D 2 Antagonist / 5-HT 2A Antagonists still have varying degrees of side effects

Method used

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  • Heterocyclic compound, preparation method therefor and use thereof
  • Heterocyclic compound, preparation method therefor and use thereof
  • Heterocyclic compound, preparation method therefor and use thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0271] Preparation Example 1 Preparation of 1-(benzothiophen-4-yl)piperazine hydrochloride

[0272]

[0273] step 1:

[0274] Dissolve 2-chloro-6-fluorobenzaldehyde 1-a (500mg, 3.15mmol), N-tert-butoxycarbonylpiperazine (646mg, 3.47mmol) into N,N-dimethylformamide (5ml), Under nitrogen protection, potassium carbonate (2.18g, 15.77mmol) was added at room temperature, the mixture was stirred at 80°C for 4 hours, cooled and filtered, water (20ml) was added, extracted with ethyl acetate (5ml×3), and 1N hydrochloric acid (3ml) Washing, washing with saturated aqueous sodium bicarbonate, drying over anhydrous sodium sulfate, and concentrating to obtain a solid, which was slurried with petroleum ether (50ml) for 1 hour, and filtered to obtain a pale yellow solid 1-b (1.0g, yield: 90%). 1 H-NMR (300Hz, DMSO-d 6 ): δppm 10.19(s,1H),7.52(t,1H),7.18(d,2H),3.46(t,4H),2.94(t,4H),1.39(s,9H).

[0275] Step 2:

[0276] in N 2 Under protection, compound 1-b (5g, 15.3mmol), ethyl thiogly...

preparation example 2

[0283] Preparation Example 2 Preparation of 5-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yl)pentyl methanesulfonate

[0284]

[0285] step 1:

[0286] Drop into 7-hydroxyl-3,4-dihydroquinolin-2(1H)-one 2-a (10g, 61.3mmol) in reaction bottle, add chloroform (100ml) and pyridine (10.6g, 134mmol), room temperature Stir for 10 minutes, cool down to below 0°C, slowly add trifluoromethanesulfonic anhydride (17.2g, 60.99mmol) dropwise, stir for 30 minutes, remove the ice bath, react at room temperature for 1 hour, filter out the solid, and wash with 1M hydrogen sulfate Washed twice with potassium aqueous solution and water, dried over anhydrous sodium sulfate, concentrated, and column chromatography gave light yellow solid 2-b (12 g, yield: 67%).

[0287] Step 2:

[0288] Compound 2-b (18g, 61.0mmol), bis(triphenylphosphine)palladium dichloride (3.6g, 5.12mmol) and cuprous iodide (3.96g, 20.8mmol) were put into the reaction flask, and replaced with nitrogen three times, Inject 4-penty...

preparation example 3

[0293] Preparation Example 3 Preparation of 5-(2-oxo-1,2-dihydroquinolin-7-yl)pentyl methanesulfonate

[0294]

[0295] Take the product of Preparation Example 2 (0.8g, 2.57mmol) and add 1,4-dioxane (5ml), 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (0.875mg, 3.85mmol), heated at 95°C for 3 hours, cooled the reaction solution, filtered to remove insoluble matter, added dichloromethane to the filtrate, washed with saturated sodium bicarbonate solution, sodium thiosulfate solution and saturated brine successively, anhydrous sodium sulfate Drying, concentration, and column chromatography gave a white solid (0.6 g, yield: 75%). ESI-MS(m / z):310.1[M+H] + .

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Abstract

Provided are heterocyclic compounds represented by formula (I), stereoisomers or pharmaceutically acceptable salts of said compounds, a pharmaceutical composition of said compounds, and an application of said compounds in the preparation of a drug for the prevention and/or treatment of a central nervous system disease.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry. Specifically, the present invention relates to a class of heterocyclic compounds represented by general formula (I), their stereoisomers or pharmaceutically acceptable salts thereof, their preparation methods, pharmaceutical compositions and their use in the preparation of central nervous system diseases application in medicine. Background technique [0002] Mental illness is mainly a group of nervous system diseases mainly manifested in behavioral and mental activity disorders. barriers of varying degrees. [0003] Due to the complexity of the central nervous system, existing antipsychotic drugs still have their own limitations. For example, clinically used drugs for the treatment of major depressive disorder (MDD) and anxiety have slow onset and poor efficacy; existing anti-schizophrenia drugs still cannot improve negative symptoms and cognitive impairment, or have extrapyramidal reactions...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D409/12C07D471/04C07D409/14C07D519/00C07D495/04C07D417/12C07D413/12A61K31/496A61K31/519A61K31/4709A61K31/517A61K31/538A61K31/5415A61K31/55A61P25/00A61P25/18A61P25/24A61P25/22A61P25/20A61P25/28A61P25/04A61P25/16A61P25/14
CPCC07D409/12C07D409/14C07D413/12C07D417/12C07D471/04C07D495/04C07D519/00A61P25/00A61P25/04A61P25/14A61P25/16A61P25/18A61P25/20A61P25/22A61P25/24A61P25/28A61P43/00A61K31/4709A61K31/496A61K31/517A61K31/519A61K31/538A61K31/5415C07D417/04C07D495/12
Inventor 蒋华良王震李剑峰张容霞何洋柳永建毕明浩刘正田广辉陈伟铭杨飞瀑吴春晖王瑜蒋翔锐尹敬敬王贯沈敬山
Owner SHANGHAI INST OF MATERIA MEDICA CHINESE ACAD OF SCI
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