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Propionamides compound and usage thereof

A propionamide and compound technology, applied in the field of propionamide compounds, can solve problems affecting the function of oocysts, etc.

Inactive Publication Date: 2009-12-02
EAST CHINA UNIV OF SCI & TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Falcipain1 is the first expressed Plasmodium cysteine ​​protease, and its biological research shows that it has no effect on the asexual reproduction stage of Plasmodium, but can significantly affect the function of oocysts

Method used

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  • Propionamides compound and usage thereof
  • Propionamides compound and usage thereof
  • Propionamides compound and usage thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0041] Preparation of N-benzyl-2-(R)-Bocamino-3-(1H-indol-3-yl)propionamide (compound II-1)

[0042] Mix 0.62 g of N-Boc-D-tryptophan, 0.42 g of 1-hydroxybenzotriazole, 0.59 g of diisopropylethylamine, 1.27 ml of N, N-diisopropylethylamine with 10 ml of dichloro Mix and stir methane at 0°C for 1 hour, add 0.22 ml of benzylamine dropwise, raise to 20°C-30°C and stir for 48 hours; wash the organic layer with dilute acid, dilute alkali, and water respectively, dry, evaporate the solvent to dryness, and the residue column layer Analysis and separation gave 0.68 g of white solid with a yield of 84.4%. mp 142-143°C; 1 H NMR (CDCl 3 , 500MHz) δ1.39(s, 9H), 3.16(m, 1H), 3.33(m, 1H), 4.26(m, 2H), 4.41(m, 1H), 6.96(m, 3H), 7.13(t , 1H), 7.18-7.21 (m, 4H), 7.35 (d, 1H), 7.66 (d, 1H).

Embodiment 2

[0044] Preparation of N-benzyl-2-(R)-amino-3-(1H-indol-3-yl)propionamide hydrochloride (compound III-1)

[0045] Add 0.68 g of II-1 and 5 ml of saturated hydrochloric acid methanol into 10 ml of tetrahydrofuran, stir overnight at 20°C-30°C; evaporate the solvent, and wash the residue with a small amount of a mixture of chloroform and methanol (20 / 1, V / V) , 0.5 g of a yellow solid was obtained, with a yield of 87.8%. mp 214-218°C; 1 H NMR (CDCl 3 , 500MHz) δ3.16(m, 1H), 3.25(m, 1H), 4.02(s, 1H), 4.27(m, 2H), 7.00(t, 1H), 7.07-7.10(m, 3H), 7.19 -7.27 (m, 4H), 7.38 (d, 1H), 7.66 (d, 1H).

Embodiment 3

[0047] N-benzyl-2-(R)-benzylamino-3-(1H-indol-3-yl)propionamide (compound I A -1) Preparation

[0048] Dissolve 0.25 g of III-1 in ether, add 10% potassium carbonate solution, separate the ether layer, extract the water layer with ether, combine the ether layers, dry over anhydrous sodium sulfate, and concentrate. Add 0.2 g of anhydrous magnesium sulfate and 5 ml of dichloromethane to the concentrate, add 0.06 ml of benzaldehyde dropwise at 20°C-30°C, stir at 20°C-30°C for 6 hours; wash with saturated sodium carbonate, and dry the organic layer; evaporate the solvent to dryness , the residue was added with appropriate amount of methanol and sodium borohydride, and stirred at 0°C for 1 hour to obtain 80 mg of yellow solid with a yield of 34%. mp 38-40°C; 1 H NMR (CDCl 3 , 500MHz) δ3.03(q, 1H), 3.38(q, 1H), 3.56-3.60(m, 2H), 3.70(d, 1H), 4.44(d, 2H), 6.95(d, 1H), 7.00 -7.02(m, 2H), 7.11(t, 1H), 7.17-7.23(m, 6H), 7.26-7.33(m, 4H), 7.37(d, 1H); MS(ESI) m / z 406[M +Na] + .

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Abstract

The invention relates to a propionamides compound and a usage thereof. The inventor, by carrying out SPR experiment based on Biacore and making comprehensive use of CADD, modifies the structure of a propionamide derivative and obtains an N-substituted-2-substituted amino-3-(1H-indole-3-yl) propionamides compound (the structure thereof is indicated by formula I). The falcipain-2 activity inhibiting capability of the obtained compound is tested, and the result shows that the prepared N-substituted-2-substituted amino-3-(1H-indole-3-yl) propionamides compound has strong falcipain-2 activity inhibiting capability and can be used for preparing medicaments for treating malaria caused by plasmodium.

Description

technical field [0001] The present invention relates to a propionamide compound and its use, in particular to an N-substituted-2-substituted amino-3-(1H-indol-3-yl) propionamide compound and its use. Background technique [0002] Malaria is one of the most frequent parasitic diseases on the planet. It is a potentially fatal disease transmitted by Anopheles mosquitoes. With the continuous increase of drug resistance to existing antimalarial drugs, the incidence of malaria is increasing, and the discovery of new antimalarial drugs with therapeutic effects is urgently needed. [0003] Plasmodium in the erythrocytic stage hydrolyzes the host's hemoglobin in its acidic food vacuole to obtain the energy and amino acids needed for its own life. Biological studies have shown that the food vesicles of Plasmodium contain a series of hydrolytic enzymes, such as plasmepsins, falcipains, and falcilysins. These enzymes have emerged as potential targets for malaria chemotherapy. [0004...

Claims

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Application Information

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IPC IPC(8): C07D209/20C07D417/12A61K31/404A61P33/06
CPCY02A50/30
Inventor 蒋华良李剑黄瑾李洪林朱进陈曈卢伟强车鹏刘彦青张燕燕陈莉莉沈旭洛夫希金弗
Owner EAST CHINA UNIV OF SCI & TECH
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