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Benzoazepine compound, preparation method and application thereof

A technology of benzonitrogen and compounds, applied in the fields of drug addiction, medicinal chemistry, and treatment of neurological diseases, can solve problems such as addiction

Inactive Publication Date: 2014-09-10
FUDAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, there is no drug addiction drug targeting dopamine receptors clinically. Therefore, the development of antagonists acting on dopamine receptors is of great significance for the treatment of drug addiction; and the search for structurally novel dopamine D 1 receptor, D 3 Receptor antagonists, which may be developed as potential drugs for the treatment of drug addiction

Method used

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  • Benzoazepine compound, preparation method and application thereof
  • Benzoazepine compound, preparation method and application thereof
  • Benzoazepine compound, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0087] Example 1: 1-benzyl-2-methoxy-4-(2-nitrovinyl)benzene ( 2 )

[0088] Add vanillin (50 g, 0.33mol) at room temperature, K 2 CO 3 (68.1g, 0.50mol) in methanol (200mL) solution was added dropwise benzyl chloride (49.2mL, 0.43mol), stirred and refluxed for 8 h after the dropwise addition, after the reaction was detected by TLC, filtered and evaporated under reduced pressure to remove the solvent. Then add water (100mL), extract with ethyl acetate (3×100L), wash the organic phase twice with 15% sodium hydroxide and water, anhydrous magnesium sulfate, filter and concentrate to obtain white solid benzyl ether (75g. 93.8%). 4-Benzyloxy-3-methoxyvanillin (50g, 0.21mol) and ammonium acetate (32.4g, 0.42mol) were added to nitromethane (23ml, 0.42mol), then 80 o C for 1.5 h. After the reaction was detected by TLC, it was cooled to room temperature, and a mixture of ice and water was added, a large amount of yellow solid precipitated, filtered, the solid was washed with water ...

Embodiment 2

[0089] Example 2: 1-benzyl-2-methoxy-4-(2-nitroethyl)benzene ( 3 )

[0090] at 0°C to contain KBH 4 (4.73g, 87.6mmol) in methanol solution (50ml) was added dropwise the compound dissolved in 80mlTHF 2 (10 g, 35.1 mmol), stirred at 50 °C for 3-4 h, distilled off the solvent under reduced pressure, extracted with ethyl acetate (3 × 50 mL), washed the organic phase three times with brine, anhydrous Na 2 SO 4 Drying, filtration, concentration, and column chromatography (petroleum ether: ethyl acetate = 5:1) gave a white solid 3 (6.1 g, yield 60.5%).

Embodiment 3

[0091] Example 3: 2-(4-benzyl-3-methoxyphenyl)acetic acid ( 4a )

[0092] compound 3 (7.2g, 25.1mmol) was dissolved in a mixed solution of acetic acid (14ml) and DMSO (50ml), added sodium nitrite (5.2g, 75.2mmol), and stirred at 45°C for 12h. After the reaction was detected by TLC, acidify with 10% hydrochloric acid, add 50ml of water, extract with ethyl acetate (3 × 50ml), wash the organic phase with brine three times, and anhydrous Na 2 SO 4 Drying under low temperature, filtration, concentration, and column chromatography (petroleum ether: ethyl acetate = 5:1) gave a white solid 4a (6.1 g, yield 90%). 1 H NMR (400 MHz, CDCl 3 ) δ 7.43 (d, J = 7.4 Hz, 2H), 7.36 (t, J = 7.4 Hz, 2H), 7.29 (t, J = 7.2 Hz, 1H), 6.83 (dd, J = 5.1, 3.1 Hz, 2H), 6.75 (dd, J = 8.2, 1.9 Hz, 1H), 5.14 (s, 2H), 3.88 (s, 3H), 3.57 (s, 2H).

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Abstract

Belonging to the field of pharmaceutical chemistry, the invention relates to a benzoazepine compound, a preparation method and application thereof, in particular to the benzoazepine compound, its preparation method and application in the field of treatment of nervous system diseases, especially application in the field of drug addiction related to dopamine D1 and D3 receptors. The benzoazepine compound and pharmacologically acceptable inorganic or organic salts thereof have a structure shown as formula (I). Results of drug experiments carried out by the invention show that the benzoazepine compound and its pharmacologically acceptable inorganic or organic salts have high antagonistic activity on dopamine D1 and D3, can be used as drug leads for further development of dopamine receptor antagonists with good selectivity and high activity, and can be used as potential drugs for treatment of drug addiction by dopamine D1, D3 receptor antagonists. (formula (I)).

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and relates to benzazepine compounds, a preparation method and applications thereof, in particular to benzazepine compounds, a preparation method, and the field of treating nervous system diseases, in particular to dopamine D 1 and D 3 Applications in the field of receptor-related drug addiction. Background technique [0002] Drug Addiction is a chronic, relapsing disease characterized by the uncontrolled use of an addictive drug. It is currently known that once exogenous opioids (such as morphine and heroin) become addicted, withdrawal is extremely difficult; it has been reported in the literature that the relapse rate of drug abuse in my country is over 95%, which not only severely damages the physical and mental health of drug abusers Health, but also a heavy burden on the family and society. Although there are many effective symptomatic treatments, no long-term effective drugs with low si...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04C07D491/147A61K31/55A61P25/30
CPCC07D471/04C07D491/147C07D498/22
Inventor 付伟杜鹏镇学初
Owner FUDAN UNIV
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