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1,2,4-thiadiazole-3,5-dione derivatives, and pharmaceutical composition and application thereof

A compound, C2-C8 technology, used in drug combinations, anti-tumor drugs, cardiovascular system diseases, etc.

Inactive Publication Date: 2014-08-20
JIANGSU SIMOVAY PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] At present, there is no compound that can inhibit both the activity of glycogen synthesis kinase-3β and the activity of acetylcholinesterase. Therefore, it is of great significance to develop such compounds

Method used

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  • 1,2,4-thiadiazole-3,5-dione derivatives, and pharmaceutical composition and application thereof
  • 1,2,4-thiadiazole-3,5-dione derivatives, and pharmaceutical composition and application thereof
  • 1,2,4-thiadiazole-3,5-dione derivatives, and pharmaceutical composition and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0211] Embodiment 1: the synthesis of compound S1

[0212] synthetic route:

[0213]

[0214] Synthesis of step 1 benzyl thioisocyanate

[0215] Benzylamine (9.63g, 90mmol) and triethylamine (18.18g, 180mmol) were mixed and dissolved in dichloromethane, and carbon disulfide (9g, 120mmol) was added dropwise under stirring in an ice bath, and stirred for 1h under ice bath after dropping, Then add triphosgene (8.82g, 0.30mol), stir at room temperature for 4h, wash with saturated aqueous sodium bicarbonate solution, dry the dichloromethane layer with anhydrous sodium sulfate, perform column chromatography, and elute with petroleum ether to obtain a colorless and transparent solution 11.18 g, yield 83.2%.

[0216] Synthesis of Step 2 Raw Material A

[0217] Triphosgene (BTC, 1.78g, 6mmol) was dissolved in chloroform, and a mixed solution of DIPEA (4.65g, 36mmol) and N-Boc piperidin-4-amine (4.0g, 20mmol) was added dropwise under ice cooling. Stir overnight in an ice bath, w...

Embodiment 2

[0224] Embodiment 2: the synthesis of compound S2

[0225] synthetic route:

[0226]

[0227] Synthesis of Step 1 Raw Material C

[0228] Dissolve piperidine-4-ethanol (1.8g, 14mmol) and DIPEA (3.6g, 28mmol) in 20ml of anhydrous acetonitrile, add benzyl bromide (2.38g, 14mmol) dropwise, and heat to reflux overnight. TLC monitors the raw material Disappeared, reaction liquid column chromatography, petroleum ether: ethyl acetate = 1:1, 2.3g of transparent oil was obtained, yield 75.01%, ESI-MS: 220.1 [M+H] + ;

[0229] Synthesis of Step 2 Intermediate D

[0230] Intermediate C (2.19g, 10mmol) was dissolved in 5ml of DMF, carbon tetrabromide (6.54g, 20mmol) was added, triphenylphosphine (5.24g, 20mmol) was added dropwise under ice-cooling, and stirring was completed under ice-bath After 20 min, stirring at room temperature overnight, column chromatography petroleum ether: ethyl acetate = 8:1 ~ 6:1, 1.5 g of yellow transparent oil was obtained with a yield of 53.38%.

[0...

Embodiment 3

[0239] Embodiment 3: the synthesis of compound S3

[0240] synthetic route:

[0241]

[0242] Synthesis of Step 1 Intermediate F

[0243] Dissolve piperidine-4-propanol (2.86g, 20mmol) and DIPEA (5.16g, 40mmol) in 20ml of anhydrous acetonitrile, add benzyl bromide (6.8g, 40mmol) dropwise, heat to reflux overnight, monitor by TLC The raw material disappeared, the reaction liquid column chromatography, petroleum ether: ethyl acetate = 1:1, 3.5 g of transparent oil was obtained, the yield was 75.11%, ESI-MS: 234.2 [M+H] + ;

[0244] Synthesis of Step 2 Intermediate G

[0245] Intermediate F (2.33g, 10mmol) was dissolved in 5ml of DMF, carbon tetrabromide (6.54g, 20mmol) was added, triphenylphosphine (5.24g, 20mmol) was added dropwise under ice-cooling, and stirring was completed under ice-bath After 20 min, stirring at room temperature overnight, column chromatography petroleum ether: ethyl acetate = 8:1 ~ 6:1, 1.83 g of yellow transparent oil was obtained with a yield of...

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PUM

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Abstract

The invention discloses 1,2,4-thiadiazole-3,5-dione derivatives, and a pharmaceutical composition and application thereof. The 1,2,4-thiadiazole-3,5-dione derivatives are compounds capable of inhibiting the activity of glycogen synthase kinase-3beta and also capable of inhibiting the activity of acetylcholinesterase, have double activity, have important potential treatment value, and have wide application to prepare medicines for treating tumors, cardiovascular diseases, cerebrovascular diseases or dementia.

Description

technical field [0001] The present invention relates to the field of medicinal chemistry, in particular to a class of 1,2,4-thiadiazole-3,5-dione compounds or pharmaceutically acceptable salts thereof and a compound containing the compound or pharmaceutically acceptable salts thereof A pharmaceutical composition, relating to the compounds or their pharmaceutically acceptable salts and the pharmaceutical compositions comprising the compounds or their pharmaceutically acceptable salts as glycogen synthesis kinase-3β inhibitors or / and acetylcholinesterase inhibitors Application, especially in the preparation of medicines for treating tumors, cardiovascular diseases, cerebrovascular diseases or dementia. Background technique [0002] Alzheimer's disease is a degenerative disease of the central nervous system characterized by chronic, progressive cognitive impairment and memory impairment. The main pathological features are senile plaques, neurofibrillary tangles and neuron loss,...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D417/04C07D417/06C07D417/14A61K31/454A61P35/00A61P9/00A61P25/28
CPCC07D417/04C07D417/06
Inventor 王磊龚兆龙张正平李福龙陈荣杨士豹
Owner JIANGSU SIMOVAY PHARMA
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