Oleanolic acid-3-one derivative having antitumor effects, preparation method, and application thereof

An anti-tumor effect, oleanolic acid technology, applied in the field of medicine, can solve the problems of weak activity, limited application, low bioavailability and the like

Active Publication Date: 2017-02-01
SHENYANG PHARMA UNIVERSITY
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0002] Oleanolic acid is a pentacyclic triterpenoid compound widely distributed in nature, which has many important biological activities, such as anti-tumor, anti-HIV virus, liver protection, anti-inflammation, etc., but its activity is weak and its bioavailability low degree, which limits its clinical application

Method used

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  • Oleanolic acid-3-one derivative having antitumor effects, preparation method, and application thereof
  • Oleanolic acid-3-one derivative having antitumor effects, preparation method, and application thereof
  • Oleanolic acid-3-one derivative having antitumor effects, preparation method, and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Example 1: Oleanolic acid-3-keto-(1'-phenyl-1H-1',2',3'-triazol-4'-yl)methyl ester (T1)

[0028] Oleanolic acid 1 (2.0g, 4.4mmol), K 2 CO 3 Powder (1.8g, 13.1mmol) and TBAB (290.0mg, 0.9mmol) were dissolved in a mixed solution of 1mL water and 200mL dichloromethane, propargyl bromide (1.0g, 8.8mmol) was added, and the reaction was stirred at room temperature for 5h, Water washing, saturated NaCl washing, anhydrous NaSO 4 Drying, filtration, concentration, and column chromatography (petroleum ether: ethyl acetate = 9:1) yielded 1.93 g of white solid 2 with a yield of 89.1%.

[0029] Compound 2 (3.0 g, 6.0 mmol) was dissolved in 50 mL of acetone, and Jones reagent (2.3 mL, 12.0 mmol) was slowly added dropwise at 0°C. Stir the reaction for 30 minutes, filter with suction, distill off acetone, add 80 mL of ethyl acetate to dissolve, and wash with water (2×10 mL). The organic layer was concentrated and purified by column chromatography (petroleum ether: ethyl acetate = 5...

Embodiment 2

[0032] Example 2: Oleanolic acid-3-keto-[1'-(2"-fluorophenyl)-1H-1',2',3'-triazol-4'-yl]methyl ester (T2 )

[0033] The preparation method of the compound in Example 2 was the same as in Example 1, except that o-fluorophenyl azide was used instead of phenyl azide to obtain T2 as a yellow solid with a yield of 88.2%.

[0034] Mp 177.5-179.6°C; 1 H NMR (600MHz, CDCl 3 )δ8.45(d, J=8.9Hz, 2H), 8.19(s, 1H), 8.00(d, J=8.9Hz, 2H), 5.32(d, J=20.0Hz, 3H), 2.90(dd, J=13.7,3.3Hz,1H),2.58-2.51(m,1H),1.14(s,3H),1.09(s,3H),1.02(s,3H),0.94(s,3H),0.94(s ,3H),0.92(s,3H),0.55(s,3H); 13 C NMR (150MHz, CDCl 3)δ217.49,177.86,147.32,144.69,143.58,141.04,126.35,125.54,122.47,122.34,120.47,57.11,55.27,47.41,46.83,46.76,45.74,41.81,41.47,39.27,39.10,36.70,34.10,33.77,33.02 ,32.37,32.16,30.66,29.70,27.62,26.38,25.66,23.57,23.44,22.97,22.69,21.44,19.49,16.65,14.88,14.12; ESI-MS(m / z):652.8[M+Na] + .

Embodiment 3

[0035] Example 3: Oleanolic acid-3-keto-[1'-(3"-fluorophenyl)-1H-1',2',3'-triazol-4'-yl]methyl ester (T3 )

[0036] The preparation method of the compound in Example 3 was the same as in Example 1, except that m-fluorophenyl azide was used instead of phenyl azide to obtain white solid T3 with a yield of 84.2%.

[0037] Mp 167.2-170.1°C; 1 H NMR (600MHz, CDCl 3 )δ8.05(s,1H),7.71(d,J=8.8Hz,2H),7.54(d,J=8.8Hz,2H),5.34-5.28(m,3H),2.90(dd,J=13.6 ,3.8Hz,1H),2.57-2.51(m,1H),1.14(s,3H),1.09(s,3H),1.04(s,3H),0.94(s,3H),0.94(s,3H) ,0.92(s,3H),0.52(s,3H); 13 C NMR (150MHz, CDCl 3 )δ217.59,177.80,144.03,143.63,135.43,134.69,129.94,122.47,122.30,121.60,57.26,55.24,47.39,46.78,45.78,41.80,41.47,39.26,39.10,36.70,34.11,33.80,33.04,32.37,32.15 ,30.67,29.70,27.62,26.46,25.65,23.58,23.44,22.96,22.69,21.43,19.51,16.66,14.88,14.12; ESI-MS(m / z):652.6[M+Na] + .

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Abstract

The invention belongs to the technical field of medicines and provides an oleanolic acid-3-one derivative which is represented as the following general formula. In the general formula, R is defined as the specification. The invention also relates to the preparation method of the compounds and potential applications of the compounds as antitumor medicines.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a preparation method and medical use of an oleanolic acid-3-one derivative containing a triazole group, in particular to a novel oleanolic acid-3-one-(1' - The preparation method of the substituted phenyl-1H-1', 2', 3'-triazol-4'-yl) methyl ester compound and its inhibitory effect on the proliferation of tumor cells have potential applications in the preparation of antitumor drugs. Background technique [0002] Oleanolic acid is a pentacyclic triterpenoid compound widely distributed in nature, which has many important biological activities, such as anti-tumor, anti-HIV virus, liver protection, anti-inflammation, etc., but its activity is weak and its bioavailability The low degree limits its clinical application. [0003] Studies have shown that oleanolic acid has different degrees of inhibitory activity on various tumor cell lines, and has a significant effect on the prevention ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07J63/00A61K31/58A61P35/00
CPCA61K31/58C07J63/008
Inventor 刘洋程卯生李凤然王帅卫高菲
Owner SHENYANG PHARMA UNIVERSITY
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