O-carborane phenol derivative as well as preparation method and application thereof

A technology of phenol derivatives and o-carborane, which is applied in the field of anti-tumor compounds, can solve the problems of limited application and low accumulation concentration of tumor tissues, and achieve the effects of reasonable route, easy control of reaction and good yield

Active Publication Date: 2016-07-20
NANJING YUANSHU MEDICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although BPA has the advantage of low chemical toxicity, its accumulation concentration in tumor tissue is low, which limits its application

Method used

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  • O-carborane phenol derivative as well as preparation method and application thereof
  • O-carborane phenol derivative as well as preparation method and application thereof
  • O-carborane phenol derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] The preparation of embodiment 1 compound 1 (2-methylbisglutamic acid phenol borane methyl ester)

[0037] Method 1: Weigh 0.5 g of 2-formylphenol borane (Tetrahedron Letters, 50 (2009) 2960–2963), add L-glutamic acid dimethyl ester hydrochloride (CAS No. 23150-65-4) 0.5 g, added to a two-necked flask and dissolved in 100ml of p-xylene, added 0.18g of sodium cyanoborohydride, 3 drops of formic acid, and the temperature was raised to 150°C for 48 hours. After the reaction was completed, the temperature dropped to room temperature. Distill the solvent under reduced pressure, add 100ml of distilled water and 100ml of dichloromethane for extraction, and add MgSO to the obtained organic phase 4 Dry, filter the mother liquor and distill under reduced pressure to obtain 0.48g, 2-methyl bisglutamic acid phenol borane methyl ester = yield 46%, calculated as 2-formyl phenol borane. The detection parameters are:

[0038] 1 H-NMR: 2.77(t, J=5.5Hz, 2H), 3.26(s, 3H), 3.43(t, J=5.5H...

Embodiment 2

[0041] The preparation of embodiment 2 compound 2 (preparation of 2-methylglutamic acid phenol borane methyl ester)

[0042] Method 1: Weigh 0.5g of 2-formylphenol borane, add 0.25g of L-dimethylglutamate hydrochloride, add it into a two-necked bottle and dissolve it in 100ml of p-xylbenzene, add cyanide 0.18g of sodium borohydride, 3 drops of formic acid, and the temperature was raised to 150°C for 48 hours. After the reaction was completed, the temperature was lowered to room temperature, the solvent was distilled under reduced pressure, and 100ml of distilled water and 100ml of dichloromethane were added for extraction. The obtained organic phase was added to MgSO 4 Dry, filter the mother liquor and distill under reduced pressure to obtain 0.47g, 2-methyl glutamic acid phenol borane methyl ester = yield 59%, calculated as 2-formyl phenol borane.

[0043] 1 H-NMR: 2.68(t, J=5.5Hz, 2H), 3.28(s, 3H), 3.41(t, J=5.4Hz, 2H), 3.45(s, 3H), 3.88(s, 2H), 5.06 (s, 1H), 6.68–6.69 (d...

Embodiment 3

[0046] The preparation of embodiment 3 compound 3 (2-methylaspartic acid phenol borane methyl ester)

[0047] Method 1: Weigh 0.5g of 2-formylphenol borane, add 0.46g of L-aspartic acid dimethyl ester hydrochloride (CAS No. 32213-95-9), add it into a two-necked bottle and dissolve in Add 0.18 g of sodium cyanoborohydride and 3 drops of formic acid to 100 ml of p-xylene, and raise the temperature to 150°C for 48 hours. Chloromethane 100ml is extracted, and the organic solvent obtained adds MgSO 4 Dry, filter the mother liquor and distill under reduced pressure to obtain 0.55 g, 2-methylaspartic acid phenol borane methyl ester = yield 71%, calculated as 2-formyl phenol borane. The detection parameters are:

[0048] 1 H-NMR: 2.71(s,2H), 3.24(s,3H), 3.40(s,2H), 3.78(s,3H), 5.01(s,1H), 6.65–6.67(d, J=8.5Hz, 1H), 7.29 (s, 1H), 7.33–7.35 (d, J=8.6Hz, 1H).

[0049] Method 2: Weigh 0.5g of 2-formylphenol borane, add 0.46g of L-aspartate dimethyl hydrochloride, add it into a two-ne...

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PUM

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Abstract

The invention discloses an o-carborane phenol derivative as well as a preparation method and application thereof. The o-carborane phenol derivative has a structural formula of (I) as shown in the specification. The preparation method comprises the following step: in an organic solvent, under enzyme and acid conditions, enabling o-carborane phenol formaldehyde and secondary amino acid ester to react so as to obtain the o-carborane phenol derivative of the formula (I), wherein the secondary amino acid ester is glutamic acid-5-methyl ester, aspartic acid methyl ester or histidine methyl ester. The invention further discloses application of the o-carborane phenol derivative. The invention discloses a novel o-carborane phenol derivative which can be accumulated in tumor cells in a high concentration manner, and has low toxicity.

Description

technical field [0001] The invention relates to an antitumor compound, especially an o-carborane phenol derivative, a preparation method and application thereof. Background technique [0002] Boron neutron capture therapy (BNCT) is a boron-containing (B 10 ) compound is injected into the human body and enters the cells through the blood circulation, because the selected boron-containing compound has affinity characteristics with cancer and tumor, and it is only enriched in diseased cancer or tumor cells. Due to the tissue barrier effect, B 10 Seldom or even can not enter the normal tissue. When a neutron beam is used to irradiate a lesion in a patient, B 10 (n,α)Li 7 The reaction produces high energy transfer linear density α particles and Li 7 Nuclei, they can kill cancer or tumor cells in the range of ≤10μ, that is, they can adopt targeting binary properties at the cellular scale (B 10 The adjustment of concentration, energy and intensity of neutron beam) is unparall...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F5/02A61K31/69A61P35/00
CPCC07F5/027
Inventor 金国范金峰郑兵王凯
Owner NANJING YUANSHU MEDICAL TECH CO LTD
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