Butyphthalide derivative as well as preparation method and application thereof

A derivative, the technology of butylphthalide, applied in the field of butylphthalide derivatives and its preparation, can solve the problems of restricting the wide application of acute cerebral ischemia, the overall curative effect is not high, and achieve low drug prices, good antithrombotic activity, chemical The effect of the simple and easy synthesis method

Active Publication Date: 2019-03-22
JIANGNAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although NBP can act on multiple pathological links of cerebral ischemia, its overall curative effect is not high, and it is often used in comb

Method used

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  • Butyphthalide derivative as well as preparation method and application thereof
  • Butyphthalide derivative as well as preparation method and application thereof
  • Butyphthalide derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0056] Example 1 Compound I 1 Preparation

[0057] Dissolve compound 3 (1.0 mmol) in 20 mL of anhydrous dichloromethane, add DCC (1.1 mmol) and a catalytic amount of DMAP with stirring, reduce by half at room temperature for 0.5 h, and then add compound 1 (1.0 mmol) for reaction at room temperature for 6-8 h . After the reaction was completed, it was filtered, concentrated under reduced pressure, and flash column chromatography (PE / EtOAc=15 / 1-5 / 1, v / v) to obtain 366 mg of orange solid product with a yield of 80%.

[0058] mp 94–96℃.MS(ESI):m / z 459.1[M+H] + .IR(cm -1 ,KBr):ν max 763,1170,1254,1492,1731. 1 H NMR(300Hz, CDCl 3 ):δ0.87(t,3H,CH 3 ,J=6.8Hz),1.26-1.50(m,4H,2×CH 2 ),1.83-1.88(m,2H,CH 2 ),2.08(s,3H,OOCCH 3 ),4.53(t,2H,OCH 2 ,J=6.0Hz),6.65(t,1H,CH,J=6.6Hz),7.40–7.44(m,3H,ArH),7.45(s,1H,C=CH),7.60–7.65(m,2H ,ArH),7.73-7.76(m,2H,ArH),8.12(d,1H,ArH,J=7.8Hz). 13 C NMR(75Hz, CDCl 3 ): δ170.4, 164.7, 153.8, 144.7, 136.1, 133.4, 130.6, 130.3, 129.4, 129.4, 128.3, 128.3, 127.4, ...

Example Embodiment

[0059] Example 2 Compound I 2 Preparation

[0060] Dissolve compound 5a (1.0 mmol) in 20 mL of anhydrous dichloromethane, add DCC (1.1 mmol) and a catalytic amount of DMAP with stirring, halve at room temperature for 0.5 h, then add compound 1 (1.0 mmol) for reaction at room temperature for 6-8 h . After the reaction was completed, it was filtered, concentrated under reduced pressure, and flash column chromatography (PE / EtOAc=15 / 1-5 / 1, v / v) to obtain 434 mg of orange oily product with a yield of 84%.

[0061] MS(ESI): m / z 502.3[M+H] + .IR(cm -1 ,KBr):ν max 764,1169,1276,1490,1739. 1 HNMR(300Hz, CDCl 3 ):δ0.85(t,3H,CH 3 ,J=6.8Hz),1.26-1.45(m,4H,2×CH 2 ),1.86-1.90(m,2H,CH 2 ),2.33(s,6H,CH 3 NCH 3 ),3.20–3.21(m,2H,OCOCH 2 N), 6.65(t,1H,CH,J=6.4Hz),7.40–7.45(m,3H,ArH),7.46(s,1H,C=CH),7.60–7.62(m,2H,ArH), 7.73–7.76(m,2H,ArH), 8.12(d,1H,ArH,J=7.8Hz). 13 C NMR(75MHz, CDCl 3 ): δ170.1, 164.7, 153.8, 144.5, 136.1, 133.3, 130.7, 130.4, 129.4, 128.3, 127.9, 127.1, 126.7, 123.3, 123.1, 72....

Example Embodiment

[0062] Example 3 Compound I 3 Preparation

[0063] Dissolve compound 5b (1.0 mmol) in 20 mL of anhydrous dichloromethane, add DCC (1.1 mmol) and a catalytic amount of DMAP with stirring, halve at room temperature for 0.5 h, then add compound 1 (1.0 mmol) for reaction at room temperature for 6-8 h . After the reaction was completed, it was filtered, concentrated under reduced pressure, and flash column chromatography (PE / EtOAc=15 / 1-5 / 1, v / v) to obtain 434 mg of orange oily product with a yield of 82%.

[0064] MS(ESI): m / z 530.2[M+H] + .IR(cm -1 ,KBr):ν max 764,1169,1400,1491,1738. 1 HNMR(300Hz, CDCl 3 ):δ0.85(t,3H,CH 3 ,J=6.8Hz),0.98(t,6H,2×NCH 2 C H 3 ,J=7.1Hz),1.26-1.45(m,4H,2×CH 2 ),1.86-1.96(m,2H,CH 2 ), 2.65(q,4H,2×NC H 2 CH 3 ,J=7.1Hz),3.32–3.47(m,2H,OCOCH 2 N),6.63(t,1H,CH,J=6.5Hz),7.40–7.43(m,3H,ArH),7.44(s,1H,C=CH),7.60–7.62(m,2H,ArH), 7.73–7.76(m,2H,ArH), 8.12(d,1H,ArH,J=7.8Hz). 13 C NMR(75MHz, CDCl 3 ): δ170.1, 164.7, 153.8, 144.7, 136.1, 133.3, 130.7, 130.4, 128.5, ...

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Abstract

The invention discloses a butyphthalide derivative as well as a preparation method and application thereof and belongs to the fields of medicinal chemistry and pharmacotherapeutics. The invention further discloses application of the butyphthalide derivative disclosed by the invention in medicines for preventing and treating ischemic cardiovascular and cerebral vascular diseases, anti-platelet aggregation drugs, antithrombotic drugs, anti-cerebral ischemia drugs, anti-dementia drugs and anti-atherosclerosis drugs. Pharmacological experiment results show that, the butyphthalide derivative disclosed by the invention has excellent anti-platelet aggregation and antithrombotic activity, and can be clinically used for preparing medicines for preventing or treating platelet aggregation related diseases.

Description

technical field [0001] The invention relates to a butylphthalide derivative, a preparation method and application thereof, and belongs to the fields of medicinal chemistry and medicinal therapeutics. Background technique [0002] Cerebral ischemia is a rapid development of brain function damage caused by the blockage of blood supply to the brain caused by ischemia. With the rapid aging of the population, the incidence of cerebral ischemia continues to increase, and it has become the world's first major cause of disability and second cause of death, and the burden on society and families has further increased. The pathogenesis of cerebral ischemia is very complex, and it is a malignant cascade process with multiple factors, mechanisms and links. Over the years, studies on the mechanisms surrounding cerebral ischemia and reperfusion injury include excitotoxicity, ion imbalance, oxidative stress, cortical diffuse depolarization, and inflammatory response. At present, the anti...

Claims

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Application Information

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IPC IPC(8): C07D339/04C07D409/12A61K31/385A61K31/4025A61K31/4535A61K31/5377A61K31/496A61K31/4178A61P7/02A61P9/10A61P9/00A61P25/28
CPCA61P7/02A61P9/00A61P9/10A61P25/28C07D339/04C07D409/12
Inventor 王晓丽尹健毕永馨尹文文
Owner JIANGNAN UNIV
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