Cinnamamide derivatives as well as preparation method and medical application thereof

A technology of phenylacrylamide and derivatives, applied in the field of phenylacrylamide derivatives or pharmaceutically acceptable salts thereof and the preparation thereof, can solve problems such as disappointing results, achieve high yield, significant anti-platelet aggregation activity, structural novel effect

Inactive Publication Date: 2017-02-22
ANHUI YIXINMING PHARMA TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Thromboxane A 2 Drug research related to diseases mostly focuses on thromboxane A 2 Inhibition of synthesis and prostaglandin (PGH 2 ), thromboxane A 2 In terms of receptor antagonism, many potent and highly selective thromboxane synthetase inhibitors have been used in clinical trials, but the results were disappointing, some people think that it is due to PGH 2 thromboxane A 2 Receptor causes platelet aggregation and vasoconstriction

Method used

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  • Cinnamamide derivatives as well as preparation method and medical application thereof
  • Cinnamamide derivatives as well as preparation method and medical application thereof
  • Cinnamamide derivatives as well as preparation method and medical application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment 1: the preparation of compound I

[0029] 1000ml dry three-necked flask, install stirrer, thermometer, add 3-buten-1-amine (28.5g,

[0030] 0.4mol), anhydrous K 2 CO 3 (58g, 0.42mol) and 310ml of dry dichloromethane, cooled to -5°C ~ 0°C, under stirring, slowly add 100ml of acryloyl chloride (36.5g, 0.4mol) in dichloromethane solution, after the addition is complete, keep warm and stir to react 1h, then warmed up to room temperature and stirred for 7h, TLC identification of the reaction end point [thin layer development conditions (petroleum ether-ethyl acetate = 10:1)], the reaction was completed, filtered, the filtrate was washed with water (3 × 50ml), anhydrous Na 2 SO 4 After drying, the desiccant was removed by filtration, and the filtrate <40°C was concentrated to dryness under reduced pressure to obtain 41.6 g of light yellow oily liquid (Intermediate 1), with a yield of 83%, which was directly used in the next step.

[0031] Intermediate 1 (41.6g,...

Embodiment 2

[0034] Embodiment 2: the preparation of compound I tartrate

[0035] Compound Ⅰ (10g, 0.0325mol) and ethanol 50ml, at room temperature, add tartaric acid (5.3g, 0.035mol),

[0036] Heat to 45°C-50°C, stir for 20min, cool to 0°C-5°C, stand overnight, filter, wash the solid with cold ethanol, and dry it under vacuum at 45°C-50°C to obtain 11.6g of white powdery solid, HPLC content 99.4%.

Embodiment 3

[0037] Embodiment 3: the preparation of compound II

[0038] Intermediate 3 (20g, 0.081mol), 120ml of anhydrous tetrahydrofuran, heated to reflux, at this time, added hexamethyldisilazane (14.5g, 0.09mol) and 11ml of triethylamine, stirred and refluxed overnight, concentrated under reduced pressure To dryness, the residue was extracted with dichloromethane (3×200ml), the combined organic layers were washed with water (3×50ml) and saturated brine (2×50ml), anhydrous Na 2 SO 4 After drying, the desiccant was removed by filtration, concentrated to dryness under reduced pressure, and recrystallized from isopropanol to obtain 9.7 g of compound II as a yellow powder solid, with a yield of 53%, mp: 236-241°C, and HPLC content of 98.2%. EIS-MS, m / z: 452[M+H] + ; 1 H NMR (400MHz, CH 3 OH-d 3 / TMS): δ H (ppm): 7.65 (t, J=15.8Hz, 2H), 7.19~7.38(m, 8H), 7.11~7.17(m, 4H), 7.02~7.10(m, 2H), 6.83(d, J=6.5 Hz, 2H), 5.57 (s, 4H), 3.39 (d, J=5.9Hz, 4H).

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Abstract

The invention belongs to the technical field of medicinal chemistry and medicines and discloses cinnamamide derivatives (I) and (II) as well as a preparation method and a medical application thereof. The novel compound has remarkable anti-platelet aggregation activity, and a new candidate medicine is provided for patients suffering from thromboembolic diseases.

Description

technical field [0001] The present invention relates to the technical fields of medicinal chemistry and medicine, in particular to phenylacrylamide derivatives represented by formula (I) or formula (II) or pharmaceutically acceptable salts thereof, their preparation methods and their use in pharmacy. Background technique [0002] Thromboxane synthase inhibitors are attracting attention as new antiplatelet agents. thromboxane A 2 and prostacyclin are active products of arachidonic acid metabolism, both of which are produced by the intermediate prostaglandin endoperoxide PGH 2 Transformed, but the biological activity is completely opposite. In platelets, PGH 2 Thromboxane A is mainly produced under the action of thromboxane synthase 2 . Prostacyclin synthase in vascular endothelial cells converts PGH 2 Convert to PGI 2 . thromboxane A 2 Is a strong platelet inducer and vasoconstrictor, and PGI 2 They are platelet aggregation inhibitors and vasodilators. Non-steroida...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/10C07D233/56A61K31/4439A61K31/4178A61P7/02
CPCC07D401/10C07D233/56
Inventor 徐奎王陈刘丽王亚丽
Owner ANHUI YIXINMING PHARMA TECH
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