CN101429175A - Perilla alcohol derivant with antineoplastic activity and uses thereof - Google Patents
Perilla alcohol derivant with antineoplastic activity and uses thereof Download PDFInfo
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- CN101429175A CN101429175A CNA2008101540177A CN200810154017A CN101429175A CN 101429175 A CN101429175 A CN 101429175A CN A2008101540177 A CNA2008101540177 A CN A2008101540177A CN 200810154017 A CN200810154017 A CN 200810154017A CN 101429175 A CN101429175 A CN 101429175A
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- perilla alcohol
- tumor
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- alcohol derivant
- antineoplastic activity
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Abstract
The invention discloses a perilla alcohol derivative with anti-tumor activity, which has a structure as right. The compound is obtained by using perilla alcohol as an initial raw material through chlorination reaction and condensation reaction. In vitro cell experiments show that the compound has propagation inhibiting effect on a cancer cell strain Lncap of human pancreas, is a potential anti-tumor medicament, and has application to preparing anti-tumor pharmaceutical preparations.
Description
Technical field
The present invention relates to a kind of perilla alcohol derivant with antitumor action, be specially 4-(1-chloro-1-methylethyl)-1-[N-(4-p-methoxy-phenyl) piperazine] tetrahydrotoluene, this compounds has characteristics such as good water solubility, anti-tumor activity height, has the purposes of preparation anti-tumor medicinal preparation.
Background technology
Human life and health in the cancer serious threat, it is one of the highest disease of mortality ratio, therefore the research of cancer therapy drug is significant and be rich in challenging field in the life science, and exploitation is efficient, the new antitumoral medicine of low toxicity, high specificity is the vital task of cancer therapy drug research.
In recent years, discover that perillalcohol (perillyl alcohol) has the anti-tumor activity height, toxicity is low, the better tolerance characteristics, and be that known a few promptly has the chemoprophylaxis effect that the natural product of chemotherapy effect is arranged again to tumour at present.In the starting stage that tumour forms, perillalcohol can not only reduce tumorigenic probability in the animal model, can also reduce tumorigenic kind, the established mammary cancer of laboratory animal, carcinoma of the pancreas, prostate cancer, liver cancer etc. all there are reverse effect, can make 81% dimethylbenzanthracene inductive rat breast carcinoma of early stage generation reverse fully.With STI571 (Gleevec, imatinib mesylate) coupling, can strengthen the curative effect of STI571 to the acute transformation phase chronic myelocytic leukemia, reverse the resistance that STI571 causes.Perillalcohol has now entered I phase and II phase clinical stage.The present invention is lead compound with the perillalcohol, and it is carried out structure of modification, might find the better compound of anti-tumor activity, and is significant to the exploitation of cancer therapy drug.
Summary of the invention
The technical problem that quasi-solution of the present invention is determined is, will have water miscible piperazine group and introduce in the perillalcohol structure, and a kind of good water solubility, perillalcohol nitrogen containing derivative that anti-tumor activity is high are provided, and then can develop the anti-cancer agent of better efficacy.
Perilla alcohol derivant structure of the present invention is as follows:
The preparation route of perilla alcohol derivant of the present invention is as follows:
Perilla alcohol derivant provided by the invention has better water solubility, the external activity test shows, this compound has strong increment to LNCaP human pancreas cancer tumour cell and suppresses active, is a kind of potential antitumor drug therefore, has the purposes of preparation anti-tumor medicinal preparation.
Embodiment
The following examples can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.
Embodiment 1:
Synthesizing of intermediate 1-chloromethyl-4-(1-chloro-1-methylethyl) tetrahydrobenzene
Perillalcohol 3.0g (0.02mol) is dissolved in the 30mL methylene dichloride, and ice bath is cooled to 0～5 ℃, stirs dripping thionyl chloride 5.8g (0.05mol) down, finishes and rises to room temperature, continues to stir 3h.Reaction solution is washed till neutrality, saturated common salt water washing with saturated aqueous sodium carbonate successively, and anhydrous sodium sulfate drying concentrates, and gets light yellow oil 2.8g, productive rate 66.7%, and this product is directly used in the next step without separation.
Embodiment 2:
4-(1-chloro-1-methylethyl)-1-[N-(4-p-methoxy-phenyl) piperazine] tetrahydrotoluene synthetic
With the product in the example 1, salt of wormwood, N-(4-p-methoxy-phenyl) piperazine in molar ratio the ratio of 1:1.5:1 feed intake, be solvent with ethanol (20mL), reflux 6h.Boil off ethanol, residuum is dissolved in the 30mL methylene dichloride, with 1N hydrochloric acid soln washing (30mL * 3), merge acid solution, anhydrous sodium carbonate is neutralized to pH9.0～10.0, dichloromethane extraction (30mL * 5), merge organic layer, use the saturated common salt water washing, anhydrous sodium sulfate drying, concentrating under reduced pressure, get yellow oil, be dissolved in acidic alcohol, leave standstill crystallization, get white crystalline solid.Product yield: 43.9%, mp:185-187 ℃.
1H-NMR?δ(ppm)：1.20(s，6H)，1.55(m，1H)，1.86-2.17(m，6H)，2.25(dd，4H，J＝4.8Hz，J＝4.8Hz)，2.89(s，2H)，3.08(dd，4H，J＝4.8Hz，J＝4.8Hz)，3.76(s，3H)，5.62(s，1H)，6.83(d，2H，J＝6.9Hz)，6.91(d，2H，J＝6.9Hz)。
With the positive contrast medicine of limonene (Limonene), measured the inhibited proliferation of this compound with mtt assay, its IC to pancreas cancer cell strain Lncap
50=41 μ M are with limonene (IC
50100 μ M) relatively, this target compound suppresses the IC of pancreas cancer cell strain Lncap
50Value increases, so this compound is expected to develop the medicine that becomes the treatment drug-resistant tumor.
Claims (3)
1. the perilla alcohol derivant with anti-tumor activity is characterized in that, this compounds is 4-(1-chloro-1-methylethyl)-1-[N-(4-p-methoxy-phenyl) piperazine] tetrahydrotoluene, structural formula is as follows:
2. the hydrochloride of described this compounds of claim 1.
3. described this compounds of claim 1 and the application of hydrochloride in anti-tumor medicinal preparation thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101540177A CN101429175B (en) | 2008-12-12 | 2008-12-12 | Perilla alcohol derivant with antineoplastic activity and uses thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2008101540177A CN101429175B (en) | 2008-12-12 | 2008-12-12 | Perilla alcohol derivant with antineoplastic activity and uses thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101429175A true CN101429175A (en) | 2009-05-13 |
| CN101429175B CN101429175B (en) | 2011-02-02 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2008101540177A Expired - Fee Related CN101429175B (en) | 2008-12-12 | 2008-12-12 | Perilla alcohol derivant with antineoplastic activity and uses thereof |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101624332B (en) * | 2009-08-12 | 2012-11-21 | 中国科学院广州生物医药与健康研究院 | New compound with anti-tumor activity and application thereof |
| CN104945333A (en) * | 2014-03-27 | 2015-09-30 | 沈阳药科大学 | Perilla alcohol analogs, and preparation and application thereof |
| CN104945334A (en) * | 2014-03-27 | 2015-09-30 | 沈阳药科大学 | Perilla alcohol derivatives, and preparation and application thereof |
| CN104945336A (en) * | 2014-03-27 | 2015-09-30 | 沈阳药科大学 | Purple perilla methyl rosmarinate nitrogen-containing derivative as well as preparation method and application thereof |
| CN112870182A (en) * | 2021-03-18 | 2021-06-01 | 中南大学 | Application of perillyl alcohol and derivatives thereof in preparation of drugs for relieving side effects of chemotherapy |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8614318B2 (en) * | 2003-11-13 | 2013-12-24 | Abbvie Inc. | Apoptosis promoters |
| CA2609202C (en) * | 2005-05-24 | 2014-12-23 | Abbott Laboratories | Apoptosis promoters |
| US20080160545A1 (en) * | 2006-09-05 | 2008-07-03 | Abbott Laboratories | Pro-GRP as a surrogate marker to predict and monitor response to Bcl-2 inhibitor therapy |
-
2008
- 2008-12-12 CN CN2008101540177A patent/CN101429175B/en not_active Expired - Fee Related
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101624332B (en) * | 2009-08-12 | 2012-11-21 | 中国科学院广州生物医药与健康研究院 | New compound with anti-tumor activity and application thereof |
| CN104945333A (en) * | 2014-03-27 | 2015-09-30 | 沈阳药科大学 | Perilla alcohol analogs, and preparation and application thereof |
| CN104945334A (en) * | 2014-03-27 | 2015-09-30 | 沈阳药科大学 | Perilla alcohol derivatives, and preparation and application thereof |
| CN104945336A (en) * | 2014-03-27 | 2015-09-30 | 沈阳药科大学 | Purple perilla methyl rosmarinate nitrogen-containing derivative as well as preparation method and application thereof |
| CN104945333B (en) * | 2014-03-27 | 2018-02-02 | 沈阳药科大学 | Perilla alcohol analog and its preparation and application |
| CN104945334B (en) * | 2014-03-27 | 2018-02-16 | 沈阳药科大学 | Perilla alcohol derivant and its preparation and application |
| CN104945336B (en) * | 2014-03-27 | 2018-02-16 | 沈阳药科大学 | Perillic acid methyl esters nitrogen containing derivative and its preparation and application |
| CN112870182A (en) * | 2021-03-18 | 2021-06-01 | 中南大学 | Application of perillyl alcohol and derivatives thereof in preparation of drugs for relieving side effects of chemotherapy |
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| Publication number | Publication date |
|---|---|
| CN101429175B (en) | 2011-02-02 |
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