3-acylamino-N-arylbenzamide compound as well as preparation and application thereof

An arylbenzamide and amide technology, applied in the field of medicine, can solve problems such as sequelae, and achieve the effect of raising the seizure threshold, improving the therapeutic effect, and reducing the level of epileptic seizures and mortality.

Inactive Publication Date: 2018-11-23
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therapies such as surgical resection of lesions can only be effective for some patients, and there is a high possibility of sequelae

Method used

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  • 3-acylamino-N-arylbenzamide compound as well as preparation and application thereof
  • 3-acylamino-N-arylbenzamide compound as well as preparation and application thereof
  • 3-acylamino-N-arylbenzamide compound as well as preparation and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0048] Example 1 3-(3-(thiophene-2-carboxamido)benzamido)methyl benzoate

[0049]

[0050] Step A: Add thiophene-2-carboxylic acid (1.024 g, 8 mmol) into a 25 mL one-necked bottle, add thionyl chloride (5 mL), and heat up to reflux for 1 hour. After the reaction, the thionyl chloride was removed under reduced pressure, the oil pump was drained, anhydrous tetrahydrofuran was added to dissolve, and 3-aminobenzoic acid (1a) (1.097g, 8mmol) (1.097g, 8mmol) and triethylamine (0.808 g, 8mmol), reacted at room temperature for 2 hours. After the reaction, THF was removed under reduced pressure, the residue was added with water and extracted three times with 10 mL of ethyl acetate, the organic phase was washed three times with 10 mL of saturated brine, the organic phase was removed under reduced pressure for ethyl acetate, and the oil pump was drained to obtain a white solid 3-( Thiophene-2-carboxamido)benzoic acid (2a), yield 95%.

[0051] Step B: Dissolve 3-aminobenzoic acid (1a...

Embodiment 2

[0054] Example 2 Ethyl 3-(3-(thiophene-2-carboxamido)benzamido)benzoate

[0055]

[0056] Synthesis steps Referring to Example 1, 5b was synthesized using 3-aminobenzoic acid, ethanol, and thiophene-2-carboxylic acid as raw materials.

[0057] Compound 5b NMR data 1 HNMR (400MHz, Acetone-d 6 )δ9.81(s,1H),9.73(s,1H),8.51(s,1H),8.36(s,1H),8.19(d,J=8.1Hz,1H),8.06(d,J=8.0 Hz,1H),7.99(d,J=3.6Hz,1H),7.79(m,3H), 7.51(m,2H),7.28–7.12(m,1H),4.37(q,J=7.1Hz,2H ),1.38(t,J=7.1Hz,3H); 13 CNMR (100MHz, Acetone-d 6 )δ166.58,166.37,160.98,141.08,140.62,140.24,136.73,132.48,132.01, 129.75,129.44,128.77,125.35,125.31,124.06,123.44,121.81,120.32,61.54,14.60;ESI-MS:m / z =395 [M+1 + ].

Embodiment 3

[0058] Example 3 3-(3-(thiophene-2-carboxamido)benzamido)isopropyl benzoate

[0059]

[0060] Synthesis steps Referring to Example 1, 5c was synthesized using 3-aminobenzoic acid, isopropanol, and thiophene-2-carboxylic acid as raw materials.

[0061] Compound 5c NMR data 1 HNMR (400MHz, Acetone-d 6 )δ9.80(s,1H),9.72(s,1H),8.48(s,1H),8.35(s,1H),8.19(d,J=8.0Hz,1H),8.06(d,J=8.1 Hz,1H),7.99(d,J=3.4Hz,1H),7.81(d,J=4.8Hz,1H),7.77(d,J=7.7Hz,2H),7.50(t,J=7.9Hz, 2H), 7.25(m, 1H), 5.35–5.07(m, 1H), 1.37(d, J = 6.2Hz, 6H); 13CNMR (100MHz, Acetone-d 6 )δ166.35,166.08,160.96,141.08,140.58,140.25, 136.75,132.48,132.39,129.75,129.70,129.43,128.77,125.34,125.26,124.03,123.42,121.81, 120.31,68.99,22.10;ESI-MS:m / z =409[M+1 + ].

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Abstract

The invention provides a 3-acylamino-N-arylbenzamide compound and pharmaceutically acceptable salt thereof. The synthesis of the compound is divided into different synthetic blocks by adopting a convergent synthetic route and a target compound can be quickly prepared in batches through docking combination. The experiment proves that the compound provided by the invention has the advantages that the epileptic seizure latency induced by pentylenetetrazol can be significantly prolonged and the grade and mortality rate of epileptic seizures are reduced; a threshold of epileptic seizure induced bymaximum electroshock can be significantly increased and the mortality rate is reduced; in addition, a seizure threshold of refractory epilepsy can be obviously increased; besides, no obvious toxic orside effects are found, which indicates that the 3-acylamino-N-arylbenzamide compound can relieve or control epileptic seizures or even has a certain therapeutic effect on the refractory epilepsy which cannot be effectively treated by traditional drugs, so that the compound can be applied to the preparation of antiepileptic drugs. The compound disclosed by the invention has the advantages of easily-obtained raw materials for synthesizing, simple operation, high process scalability, suitability for industrial production and capability of providing a novel drug for epilepsy treatment. The structure of a general formula I is shown in the description.

Description

technical field [0001] The invention belongs to the field of medicine, and provides 3-amido-N-arylbenzamide compounds and their pharmaceutically acceptable salts, their preparation, and their medical use, especially their application in antiepileptic drugs. Background technique [0002] Epilepsy (epilepsy) is a common clinical nervous system disease, and its incidence rate is about 1%. At present, there are about 70 million epilepsy patients in the world, and there are more than 10 million epilepsy patients in China. Epilepsy is characterized by epileptic seizures caused by abnormally synchronized discharge of neurons in the brain. If the seizures are not controlled, it will cause serious harm to the patient's quality of life and even life safety. Drugs are currently used clinically to control epileptic seizures. Traditional antiepileptic drugs mainly act on ion channels on neurons or γ-aminobutyric acid receptors to reduce the excitability in the brain, but about one-thi...

Claims

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Application Information

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IPC IPC(8): C07D333/38A61P25/08
CPCA61P25/08C07D333/38
Inventor 陈忠徐层林汪仪崔孙良
Owner ZHEJIANG UNIV
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