8-substitued oxoisoaporphine derivatives as well as synthetic method and application thereof

A technology of isoapofil and synthesis method, applied in the field of 8-substituted oxidized isoapofil derivatives and its synthesis, can solve problems that have not been seen before, and achieve good medicinal value and strong inhibitory activity

Inactive Publication Date: 2014-07-16
GUANGXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patented compound has been found effective against certain enzymes involved in brain functioning such as Acetyl Choline esterase (Acetic acid) or Butyratecholatesterase (Butyric acid). It can also reduce other substances like dopamine released from nerve cells called neurons which help control their behavioral functions during agitation movements. These properties make it useful in treatments targeted at prevention/treatment of various conditions associated with cognitive declination including Alzheimers Dementum, Cognositis, Parkinsonism, Huntington’ s disease, stroke, epilepsies, schizophrenics disorders, anxiety states, autism spectrum syndrome, drug dependence, alcohol abuse, narcoleptic attacks etc., making them potentially valuable tools for research purposes.

Problems solved by technology

This patents discuss how different chemical substances called acetochelins play a crucial part in maintaining normal neurological processes during aggression disorders like Parkinsonism/Alcoholysis Neuropathology Disorder Type I (Parkerian Syndrome). Acute phase therapy involves administering agents specifically designed to reduce excess levels of glutonium ion within certain parts of brainstem nuclei associated with neural dysfunction. These techniques aim to enhance the efficiency of current pharmaceuticals for managing pathological conditions including epilepsy, glaulence, stroke, trauma induced damage, multiple sclerosis, and glioma.

Method used

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  • 8-substitued oxoisoaporphine derivatives as well as synthetic method and application thereof
  • 8-substitued oxoisoaporphine derivatives as well as synthetic method and application thereof
  • 8-substitued oxoisoaporphine derivatives as well as synthetic method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1: Synthesis of 4-chloro-2-phenylisoindoline-1,3-dione (Compound 1)

[0034] Add 57g (0.1mol) of 3-chlorophthalic anhydride and 45g (0.1mol) of phenethylamine into a 1L three-hole round bottom flask, then add 500ml of toluene, reflux for 6 hours, pour out while it is hot, and cool. Crystals were separated out and filtered with suction to obtain compound 1 (white flake crystals) with a yield of about 98%.

[0035] Analyze compound 1 and its spectral characteristics are as follows:

[0036] 1 H NMR(CDCl 3 ,500MHz): δ3.00~3.04(m,2H),3.94~3.97(m,2H),7.23~7.34(m,5H),7.65(d,J=1.7,1H),7.66(s,1H) ,7.78(dd,J 1 =5.0and J 2 =3.2,1H);ESI-MS(m / z):287[M+H] + .

[0037] Therefore, it can be determined that the above compound 1 is 4-chloro-2-phenylisoindole-1,3-dione, and its structural formula is shown in the following formula:

[0038]

Embodiment 2

[0039] Example 2: Synthesis of 8-Cl-1-azabenzoanthrone (Compound 2)

[0040] Add 75g (0.56 mol) of anhydrous aluminum trichloride and 15g of sodium chloride into a 1L three-hole round bottom flask, mix and heat to 140℃ to melt, and then slowly add 53g (0.2mol) of compound 1 to it in batches After the addition is complete, the temperature is raised to 220°C, and the reaction is stirred for 3 hours. After being heated, it is poured into a mortar, cooled and mashed to obtain a reddish brown solid, which is placed in a drying vessel.

[0041] Take 600ml of concentrated sulfuric acid and add it to a 2L three-hole round bottom flask. When the temperature is raised to 80°C, the red-brown solid obtained above is added in batches. After the addition, the temperature is raised to 230°C, the reaction is stirred for 2.5 hours, cooled, and poured into In about 600 g of ice water, adjust the pH to about 2-3 with NaOH, precipitate a large amount of solids, filter with suction, and wash with water...

Embodiment 3

[0046] Example 3: Synthesis of 8-amino-7H-dibenzoquinolin-7-one (compound 3)

[0047] Take 1.5g of compound 2 in the inner pot of the autoclave, add 100ml of ammonia water, and react at 180°C for 12h, then stop the reaction. After cooling, adjust the pH to 7-8 with 3mol / L HCl, filter with suction, and dry. The crude product was purified by silica gel column chromatography (petroleum ether / chloroform=7:1) to obtain compound 3 (red solid) with a yield of 40%.

[0048] Analyzing compound 3, its spectral characteristics are as follows:

[0049] 1 H NMR (500MHz, DMSO): δ8.73(d,J=5.5Hz,1H), 8.45(d,J=7.2Hz,1H), 8.29(d,J=8.2Hz,1H), 8.06(d, J=8.4Hz,1H),8.02-7.97(m,1H),7.94(d,J=5.6Hz,1H),7.55-7.48(m,1H),7.00(d,J=7.3Hz,1H), 2.51(t,J=2.8Hz,2H);ESI-MS(m / z):247[M+H] + .

[0050] Therefore, it can be determined that the above compound 3 is 8-amino-7H-dibenzoquinolin-7-one, and its structural formula is shown in the following formula:

[0051]

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Abstract

The invention discloses a series of 8-substitued oxoisoaporphine derivatives as well as a synthetic method and application thereof. The synthetic method comprises the following steps: (1) performing cyclization reaction on 3-chlorophthalic anhydride and phenylethylamine as raw materials twice to construct an 8-Cl-1-azabenzanthrone matrix; (2) ammonifying the 8-Cl-1-azabenzanthrone matrix to obtain 8-amino-7H-dibenzoquinoline-7-ketone; (3) reacting 8-amino-7H-dibenzoquinoline-7-ketone with an acyl chloride compound connected with piperidine to obtain corresponding target products. A study of the applicant discovers that the derivatives have very good inhibition activity on acetylcholin esterase, have relatively good potential medicinal values and are expectedly used for treating Alzheimer diseases, cerebral vascular dementia and related diseases caused by reduction of similar cholinergic neurotransmitters. The structure of the 8-substitued oxoisoaporphine derivatives is shown in a formula.

Description

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Claims

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Application Information

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Owner GUANGXI NORMAL UNIV
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