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Praziquantel analogue, preparation method and application thereof

A scheme and compound technology, applied in the field of praziquantel analogs, can solve the problems such as the prevalence of praziquantel-resistant strains and the poor treatment effect of schistosomiasis adults

Inactive Publication Date: 2014-07-09
JIANGNAN UNIV +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

If it continues to be used on a large scale, it is very likely that praziquantel-resistant strains will become prevalent. In the absence of new effective drugs for the treatment of schistosomiasis, it will bring serious difficulties and challenges to the future treatment of schistosomiasis worldwide.
Although the antimalarial drug artemisinin developed in my country has a certain therapeutic effect on schistosomiasis larvae, its therapeutic effect on schistosomiasis adults is relatively poor

Method used

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  • Praziquantel analogue, preparation method and application thereof
  • Praziquantel analogue, preparation method and application thereof
  • Praziquantel analogue, preparation method and application thereof

Examples

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Effect test

preparation example Construction

[0072] The preparation method of compound among the following preparation examples 1-11 mainly comprises following eight reaction operations:

[0073] React operation 1:

[0074]

[0075] Compound 1 was mixed with 2N HCl aqueous solution and heated to 110°C overnight. After the reaction was completed, neutralization, extraction, and concentration were performed to obtain reactant 2. Afterwards, the reactant 2 (FWH202.2) (1.0eq) was dissolved in dichloromethane, and the acid chloride (R 4 COCl) (1.5eq), triethylamine (TEA) (1.0eq), and TLC to track and determine the degree of completion of the reaction. After the reaction was completed, compound 3 was obtained by extraction, concentration of the reaction solution to remove the solvent, and column chromatography.

[0076] where R 4 is unsubstituted or fluorine or chlorine substituted C 2 -C 5 Alkyl; C 3 -C 6 Cycloalkyl; cyclohexenyl; unsubstituted or substituted phenyl, the substituents are selected from C 1 -C 3 1-3 ...

Embodiment 1

[0110]

[0111] Compound 1 (10.0g, 32mmol) was added to HCl aqueous solution (2N, 50mL), then heated to 110°C and refluxed overnight. After the reaction, the aqueous phase was extracted with ethyl acetate to remove impurities, and the aqueous phase was washed with sodium bicarbonate ( NaHCO 3 ) saturated aqueous solution was neutralized to alkaline, extracted (DCM:MeOH=10:1), concentrated to remove the solvent to obtain compound 2 (4.0 g, yield 62.5%). Compound 2 (500mg, 2.5mmol) was dissolved in dichloromethane (DCM) (10mL), and benzoyl chloride (520mg, 3.75mmol), triethylamine (TEA) (250mg, 2.5mmol) were added at 0°C After the addition, stir at room temperature, TLC to track and measure the degree of completion of the reaction. After the reaction is completed, add a saturated aqueous solution of sodium bicarbonate, extract with ethyl acetate, concentrate to remove the solvent, and use petroleum ether / ethyl acetate (volume ratio 1:1 ) column chromatography to obtain compo...

Embodiment 2

[0119]

[0120] Dissolve compound 2 (300mg, 1.5mmol) in methanol (10mL), add cyclohexaneformaldehyde under ice bath, add glacial acetic acid (180mg, 3mmol) after 40min, raise the reaction temperature to room temperature, stir for 1h, then heat Stir at 60°C for 2h, then cool down to 0°C, add sodium borohydride (450mg, 12mmol) in batches, heat to 60°C overnight after addition. Then the reaction system was cooled to room temperature, quenched with water, the reaction solution was concentrated to remove the solvent, extracted, and separated by petroleum ether / ethyl acetate (volume ratio 2:1) column chromatography to obtain compound 4-1 (FWH298.42) (140mg , yield 32%).

[0121] 1 HNMR (400MHz, CDCl 3 )δ:1.58-1.83(m,6H),1.69-1.79(m,7H),2.75-2.99(m,5H),3.02-4.39(m,2H),4.79-4.90(m,2H),7.16- 7.28(m,4H).ESI-MS(m / s):299[M+1] +

[0122] Except replacing the cyclohexyl formaldehyde in embodiment 2 with following corresponding reaction compound, synthesize following compound with th...

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Abstract

The invention provides a compound shown as the structural formula I, a preparation method and application thereof. The compound has polypide paralysis and insecticidal effects, can be used for preparing anti-schistosomiasis drugs, and overcomes poor curative effect or ineffective treatment phenomenon for the reason of drug resistance caused by long-term use of the anti-schistosomiasis drugs in the prior art. The compound has the advantages of simple structure and easy preparation.

Description

technical field [0001] The present invention belongs to the field of medicinal chemistry, and relates to a class of praziquantel analogues with the structure shown in general formula I, their preparation method and application. The compounds have anti-schistosome physiological activity and can improve the drug resistance of praziquantel. Provide new means for the prevention and treatment of schistosomiasis. Background technique [0002] Schistosomiasis is still an important zoonotic parasitic disease that seriously endangers human health, and is an important public health problem in tropical and subtropical regions. The schistosomes that parasitize humans include: Schistosoma japonicum, Schistosoma mansoni, Schistosoma haematobium, Schistosoma indirect and Schistosoma brow. Schistosomiasis is prevalent in about 76 countries in the world, more than 600 million people are threatened by schistosomiasis infection, 20 million people are infected with schistosomiasis, and more th...

Claims

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Application Information

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IPC IPC(8): C07D471/04C07D495/14C07D217/06C07D409/06C07D401/06A61K31/4985A61K31/472A61K31/4725A61P33/12
CPCC07D217/06C07D401/06C07D409/06C07D471/04C07D495/14Y02A50/30
Inventor 余传信冯柏年宋丽君王文龙
Owner JIANGNAN UNIV
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