CN101550098B - 4-isothio-urea-butyronitrile hydrochloride and application of derivatives thereof - Google Patents
4-isothio-urea-butyronitrile hydrochloride and application of derivatives thereof Download PDFInfo
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- CN101550098B CN101550098B CN200910000238.3A CN200910000238A CN101550098B CN 101550098 B CN101550098 B CN 101550098B CN 200910000238 A CN200910000238 A CN 200910000238A CN 101550098 B CN101550098 B CN 101550098B
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- isothio
- urea
- butyronitrile
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Abstract
The invention relates to a 4-isothio-urea-butyronitrile and derivatives thereof, and the structural formula is shown in the formula I and II. The 4-isothio-urea-butyronitrile and derivatives thereof provided by the invention have better inhibiting effect on human ovarian cancer cells, hepatocarcinoma cells, lung cancer cells and human gastric carcinoma cells, wherein IC50=4.69x10<-6>g/mL, 3.98x10<-6>, 2.12x10<-6> and 3.31x10<-6>g/mL; and the 4-isothio-urea-butyronitrile and derivatives thereof can be applied in preparing anti-cancer drugs for resisting ovarian carcinoma, hepatocellular carcinoma, lung carcinoma and human gastric carcinoma cells.
Description
Technical field
The present invention relates to a kind of Compound C (4-isothio-urea-butyronitrile, 4-Isothiouriedobutyronitrile hydrochloride) and derivative thereof, specifically relate to a kind of 4-isothio-urea-butyronitrile purposes.
Background technology:
Malignant tumour is the killer who threatens human health always.The active cancer therapy drug better, that toxic side effect is lower of exploitation is imperative.Compound C (4-isothio-urea-butyronitrile, 4-Isothiouriedobutyronitrile hydrochloride) and derivative thereof, have certain curative effect to its malignant tumours such as ovarian cancer, liver cancer, lung cancer and cancer of the stomach.
Summary of the invention
The object of the present invention is to provide the purposes of a kind of Compound C (4-isothio-urea-butyronitrile) and derivative thereof.
The object of the invention is to realize by the following technical solutions:
A kind of Compound C (4-isothio-urea-butyronitrile) and derivative thereof are provided, and structural formula is suc as formula shown in I and II.
The preparation of Compound C (4-isothio-urea-butyronitrile) and derivative thereof, its synthetic route is as follows:
Synthesizing of Compound C (4-isothio-urea-butyronitrile)
Sulphur urine (38.1g, 0.5mo1) with 4-chlorobutyronitrile (60g, aqueous solution backflow 3h 0.55mo1), remove under reduced pressure after water, vacuum-drying (> 1Torr) obtains Compound C (mp126-128 ℃), Compound C is again through methyl alcohol: after acetone (1: 3) mixed solvent recrystallization, fusing point is 132-133 ℃.Productive rate is 59%
Compound C provided by the invention (4-isothio-urea-butyronitrile) and derivative thereof have good restraining effect to Proliferation of Human Ovarian Cell, liver cancer cell, lung carcinoma cell and gastric carcinoma cells, and its IC50 is respectively 4.69x10
-6g/mL, 3.98x10
-6, 2.12x10
-6and 3.31x10
-6g/mL, can be applicable to prepare the medicine of ovarian cancer resistance tumour, liver cancer tumour, lung cancer tumour and cancer of the stomach tumour.
The present invention has found that Compound C (4-isothio-urea-butyronitrile) and derivative thereof have antitumour activity.
Accompanying drawing explanation
Fig. 1 is Compound C of the present invention (4-isothioureido butyronitrile) and derivant structure formula formula I and II.
Embodiment
The reagent such as sulphur urine, 4-chlorobutyronitrile in following embodiment is purchased from Beijing reagent company, and solvent is purchased from Beijing Chemical Plant.
Synthesizing of embodiment 1 Compound C (4-isothio-urea-butyronitrile) and derivative thereof
Synthesizing of Compound C (4-isothio-urea-butyronitrile)
Sulphur urine (38.1g, 0.50mo1) with 4-chlorobutyronitrile (60g, aqueous solution backflow 3h 0.55mo1), remove water under reduced pressure, further vacuum (> 1Torr) is dried to obtain Compound C (mp126-128 ℃), Compound C is again through methyl alcohol: after acetone (1: 3) mixed solvent recrystallization, fusing point is 132-133 ℃.Productive rate is 55%.
Compound C: m.p.132-133 ℃, R
f=0.56 (CH
2c1
2: CH
3oH)=5: 2).
IR(KBr)v/cm
-1：3329，3257，3087，2250(CN)，1652。
1H?NMR(400MHz，CD
3OD)6：1.96(2H，dt，J＝10.9，7.2Hz，3-H)，2.54(2H，t，J＝7.2Hz，4-H)。
13C?NMR(100MHz，CD
3OD)6：170.8
118.7(C-1)，29.2(C-3)，24.7(C-4)，15.0(C-2)。
Ultimate analysis (%, C
5h
10clN
3s) calculated value: C, 33.43; H, 5.61; N, 23.39; Measured value: C, 33.38; H, 5.54; N, 23.24.
The antitumour activity screening experiment of embodiment 2 Compound C
experiment cancer cells
Colon cancer cell (HCT-8), liver cancer cell (BEL-7402), lung adenocarcinoma cell (A549), stomach cancer cell (BGC-823) and Proliferation of Human Ovarian Cell (A2780), by Beijing, institute of materia medica provides.
Table 1 antitumour activity test-results IC
50(g/mL)
Can be found out by experimental result, Compound C has good restraining effect to Proliferation of Human Ovarian Cell (A2780), liver cancer cell (BEL-7402), lung adenocarcinoma cell (A549) and gastric carcinoma cells (BGC-823), and its IC50 value is respectively 4.69 × 10
-6, 3.98 × 10
-6, 2.12 × 10
-6with 3.31 × 10
-6g/mL, can be applicable to prepare the medicine of ovarian cancer resistance tumour, liver cancer tumour, lung cancer tumour and gastric carcinoma cells.
experimental agents
DMSO for sample to be measured (compound (C)) is dissolved, be mixed with concentration and be respectively the solution of 3mg/mL and 30mg/mL (containing DMSO≤3%), in 4 ℃ of refrigerators, preserve for testing.
substratum
PDA substratum: potato 50g, glucose 5g, agar 5g, adds water to 250ml, preparation according to a conventional method, activated spawn is used.
Sharpe liquid base (SDB): glucose 2g, protein 1g, adds water to 100mL, preparation according to a conventional method, test tube medicine base dilution experiment method is used.
experimental technique
(1) preparation of drug dilution liquid: 10 times of Sharpe liquid base dilutions for the liquid of each concentration, and then take this concentration as initial concentration, doubling dilution, the final concentration of Experimental agents concentration is 3000-46.9 μ g/mL and 3000-4.69 μ g/mL.
(2) preparation of bacteria suspension: strain subject (experiment cancer cells), through PDA substratum activation, is got bacterium colony and make bacteria suspension in 2mL distilled water, shakes 15 seconds, its concentration is adjusted to 1 × 10 with blood cell counting plate
4-2 × 10
4cFU/mL.
(3) get the drug dilution liquid preparing, to the every test tube of lower concentration, add successively 1mL solution by high density, using the Sharpe liquid base containing 3%DMS0 as solvent control, do not add medicine as blank take Sharpe liquid base, respectively each bacteria suspension 10 μ L are inoculated in test tube with transfering loop, put in 27-30 ℃ of thermostat container and cultivate.
(4) judgement of result: through constant temperature culture respectively at 24h, 48h, 72h, 96h, 124h and 148h observations, in the situation that not stirring, naked eyes are judged, the Clear & Transparent cancer cells that is considered as of solution is not grown completely, and taking entirely not growth tube lowest concentration of drug is minimum inhibitory concentration (MIC).
experimental result
Colon cancer cell (HCT-8), liver cancer cell (BEL-7402), gastric carcinoma cells (BGC-823), lung adenocarcinoma cell (A549) and Proliferation of Human Ovarian Cell (A2780), by Beijing, institute of materia medica provides.
Table 1 antitumour activity test-results IC
50(g/mL)
Can be found out by experimental result, Compound C is to Proliferation of Human Ovarian Cell (A2780), liver cancer cell (BEL-7402), lung adenocarcinoma cell (A549) and gastric carcinoma cells (BGC-823), have good restraining effect, its IC50 value is respectively 4.69 × 10
-6, 3.98 × 10
-6, 2.12 × 10
-6with 3.31 × 10
-6g/mL, can be used for preparing the medicine of ovarian cancer resistance tumour, liver cancer tumour, lung cancer tumour and gastric carcinoma cells.
Claims (2)
1.4-isothioureido butyronitrile derivative, structural formula is suc as formula shown in I, formula II
Wherein, in formula II, R
1for CH
3, C
2h
5or C
3h
7;
N=4 in formula I, 5,6,7,8,9,10,20;
N=1 in formula II, 2,3,4,5,6,7,8,9,10.
The purposes of 2.4-isothioureido butyronitrile derivative in the medicine of preparing ovarian cancer resistance tumour, liver cancer tumour, lung cancer tumour and gastric carcinoma cells, is characterized in that, described 4-isothioureido butyronitrile derivative is:
Wherein, in formula II, R
1for CH
3, C
2h
5or C
3h
7;
N=1 in formula I, 2,3,4,5,6,7,8,9,10,20;
N=1 in formula II, 2,3,4,5,6,7,8,9,10.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910000238.3A CN101550098B (en) | 2009-01-14 | 2009-01-14 | 4-isothio-urea-butyronitrile hydrochloride and application of derivatives thereof |
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| CN200910000238.3A CN101550098B (en) | 2009-01-14 | 2009-01-14 | 4-isothio-urea-butyronitrile hydrochloride and application of derivatives thereof |
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| CN101550098B true CN101550098B (en) | 2014-07-09 |
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Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102438612B (en) * | 2009-05-20 | 2016-02-03 | 塞尔休迪克斯公司 | Carbonitrile derivatives and pharmaceutical use thereof and compositions |
| US9610275B2 (en) | 2009-05-20 | 2017-04-04 | Cellceutix Corporation | Nitrile derivatives and their pharmaceutical use and compositions |
| CN113967207B (en) * | 2021-11-22 | 2023-03-21 | 重庆医科大学 | Use of 4-isothioureidobutyronitrile hydrochloride for treating mycobacterial infections |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4514418A (en) * | 1982-04-20 | 1985-04-30 | Nihon Tokushu Noyaku Seizo K.K. | 2,2-Dihalogeno-3,3-dimethylcyclopropane derivative fungicides |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62167754A (en) * | 1986-01-20 | 1987-07-24 | Roller Japan Kk | Production of cyanomethylthioacetic acids |
-
2009
- 2009-01-14 CN CN200910000238.3A patent/CN101550098B/en not_active Expired - Fee Related
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4514418A (en) * | 1982-04-20 | 1985-04-30 | Nihon Tokushu Noyaku Seizo K.K. | 2,2-Dihalogeno-3,3-dimethylcyclopropane derivative fungicides |
Non-Patent Citations (4)
| Title |
|---|
| JanaKlose.Preparationof2-(2-Cyanoethyl)sulfanyi-lH-isoindole-l 3-(2H)-dione and Related Sulfur-Transfer Agents.《Tetrahedron》.1997 |
| Preparation of 2-(2-Cyanoethyl)sulfanyi-lH-isoindole-l,3-(2H)-dione and Related Sulfur-Transfer Agents;Jana Klose;《Tetrahedron》;19971231;第53卷(第42期);第14412页 * |
| Preparation of Protein Conjugates via Intermolecular Disulfide Bond formation;Te Piao King;《preparation of protein conjugates》;19781231;第17卷(第8期);第1499页 * |
| Te Piao King.Preparation of Protein Conjugates via Intermolecular Disulfide Bond formation.《preparation of protein conjugates》.1978,第17卷(第8期),第1499页. |
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