CN101550098A - 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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- CN101550098A CN101550098A CNA2009100002383A CN200910000238A CN101550098A CN 101550098 A CN101550098 A CN 101550098A CN A2009100002383 A CNA2009100002383 A CN A2009100002383A CN 200910000238 A CN200910000238 A CN 200910000238A CN 101550098 A CN101550098 A CN 101550098A
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- isothio
- urea
- butyronitrile
- derivatives
- compound
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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 4-isothio-urea-butyronitrile 4-Isothioureidobutyronitrilehydrochloride) and derivative, specifically relates to a kind of 4-isothio-urea-butyronitrile purposes to the present invention relates to a kind of Compound C.
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.(the 4-isothio-urea-butyronitrile 4-Isothioureidobutyronitrilehydrochloride) and derivative, has certain curative effect to its malignant tumours such as ovarian cancer, liver cancer, lung cancer and cancer of the stomach to Compound C.
Summary of the invention
The object of the present invention is to provide the purposes of described Compound C (4-isothio-urea-butyronitrile) and derivative thereof.
The objective 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 the II.
n＝1，2，3，4，5，6，7，8，9，10……20
Formula I
R
1＝CH
3，C
2H
5，C
3H
7；n＝1，2，3，4，5，6，7，8，9，10
Formula 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)
(38.1g is 0.50mol) with 4-chlorobutyronitrile (60g, aqueous solution backflow 3h 0.55mol) for sulphur urine, after removing water under reduced pressure, vacuum-drying (＞1Torr) getting Compound C (mp 126-128 ℃), Compound C is again through methyl alcohol: behind acetone (1: 3) the 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 inhibitory effect to Proliferation of Human Ovarian Cell, liver cancer cell, lung carcinoma cell and gastric carcinoma cells, its IC50 is respectively 4.69 * 10-6g/mL, 3.98 * 10-6,2.12 * 10-6 and 3.31 * 10-6g/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.
Fig. 1 is the structural formula of Compound C (4-isothio-urea-butyronitrile) and derivative thereof.
Embodiment
Sulphur urine among the following embodiment, 4-chlorobutyronitrile are all purchased in Beijing reagent company, and solvent is all purchased in the 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, 0.50mol) and 4-chlorobutyronitrile (60g, 0.55mol) aqueous solution backflow 3h, after removing water under reduced pressure, further vacuum (＞1Torr) dry Compound C (mp 126-128 ℃), Compound C is again through methyl alcohol: behind acetone (1: 3) the mixed solvent recrystallization, fusing point is 132-133 ℃.Productive rate is 55%.
Compound C: m.p.132-133 ℃, R
f=0.56 (CH
2Cl
2: CH
3OH=5: 2).
IR(KBr)
3329，3257，3087，2250(CN)，1652。
1H?NMR(400MHz，CD
3OD)δ：1.96(2H，dt，J＝10.9，7.2Hz，3-H)，2.54(2H，t，J＝7.2Hz，2-H)，3.16(2H，t，J＝7.2Hz，4-H)。
13C?NMR(100MHz，CD
3OD)δ：170.8
118.7(C-1)，29.2(C-3)，24.7(C-4)，15.0(C-2).
Ultimate analysis (%, C
5H
10CIN
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
The 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), the institute of materia medica provides by Beijing.
Table 1, antitumour activity test-results IC
50(g/mL)
By experimental result as can be seen, 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 inhibitory effect, its IC50=4.69 * 10-6g/mL, 3.98 * 10-6,2.12 * 10-6 and 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.
The experiment medicine
Sample to be measured (Compound C) with the DMSO dissolving, is mixed with the solution that concentration is respectively 3mg/mL and 30mg/mL (containing DMSO≤3%), preserves for experiment in 4 ℃ of refrigerators and use.
Substratum
The PDA substratum: potato 50g, glucose 5g, agar 5g adds water to 250mL; Preparation according to a conventional method, activated spawn is used.
Sha Shi 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: the soup of each concentration is with 10 times of Sha Shi liquid base dilutions, and then is initial concentration with this concentration, and doubling dilution, the final concentration of experimental drug substrate concentration are 3000-46.9ug/mL and 300-4.69ug/mL.
(2) preparation of bacteria suspension: strain subject (experiment cancer cells) through the activation of PDA substratum, is got bacterium colony and make bacteria suspension in 2mL distilled water, shakes 15 seconds, with blood cell counting plate its concentration is transferred to 1 * 10
4-2 * 10
4CFU/mL.
(3) get the drug dilution liquid for preparing, to the every test tube of lower concentration, add 1mL solution by high density successively, with the Sha Shi liquid base that contains 3%DMSO as solvent control, not adding medicine with Sha Shi liquid base is blank, respectively each bacteria suspension 10uL is inoculated in the test tube with transfering loop, puts in the 27-30 ℃ of thermostat container and cultivate.
(4) result's judgement: through constant temperature culture respectively at 24h, 48h, 72h, 96h, 124h and 148h observations, naked eyes are judged under the situation of not stirring, the Clear ﹠ Transparent cancer cells that is considered as of solution is not grown fully, and getting fully not, the 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), the institute of materia medica provides by Beijing.
Table 1, antitumour activity test-results IC
50(g/mL)
By experimental result as can be seen, 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 inhibitory effect, its IC50=4.69 * 10-6g/mL, 3.98 * 10-6,2.12 * 10-6 and 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.
Claims (1)
1,4-isothio-urea-butyronitrile and derivative thereof, structural formula is suc as formula shown in I and the II.
n＝1，2，3，4，5，6，7，8，9，10......20
Formula I
R
1＝CH
3，C
2H
5，C
3H
7；n＝1，2，3，4，5，6，7，8，9，10
Formula II
Described 4-isothio-urea-butyronitrile of claim 1 and derivative thereof the purposes in the medicine of preparation ovarian cancer resistance tumour, liver cancer tumour, lung cancer tumour and gastric carcinoma cells.
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| Application Number | Priority Date | Filing Date | Title |
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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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|---|---|---|---|
| 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 CN101550098B (en) | 2014-07-09 |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010135170A3 (en) * | 2009-05-20 | 2011-01-13 | Cellceutix Corporation | Nitrile derivatives and their pharmaceutical use and compositions |
| US9610275B2 (en) | 2009-05-20 | 2017-04-04 | Cellceutix Corporation | Nitrile derivatives and their pharmaceutical use and compositions |
| CN113967207A (en) * | 2021-11-22 | 2022-01-25 | 重庆医科大学 | Use of 4-isothioureidobutyronitrile hydrochloride for treating mycobacterial infections |
Citations (2)
| 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 |
| 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 (2)
| 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 |
| JPS62167754A (en) * | 1986-01-20 | 1987-07-24 | Roller Japan Kk | Production of cyanomethylthioacetic acids |
Non-Patent Citations (2)
| Title |
|---|
| JANA KLOSE: "Preparation of 2-(2-Cyanoethyl)sulfanyi-lH-isoindole-l,3-(2H)-dione and Related Sulfur-Transfer Agents", 《TETRAHEDRON》 * |
| TE PIAO KING: "Preparation of Protein Conjugates via Intermolecular Disulfide Bond formation", 《PREPARATION OF PROTEIN CONJUGATES》 * |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010135170A3 (en) * | 2009-05-20 | 2011-01-13 | Cellceutix Corporation | Nitrile derivatives and their pharmaceutical use and compositions |
| CN102438612A (en) * | 2009-05-20 | 2012-05-02 | 塞尔休迪克斯公司 | Nitrile derivatives and their pharmaceutical use and compositions |
| JP2012527464A (en) * | 2009-05-20 | 2012-11-08 | セルセウティックス コーポレイション | Nitrile derivatives and their pharmaceutical uses and compositions |
| US8338454B2 (en) | 2009-05-20 | 2012-12-25 | Cellceutix Corporation | Nitrile derivatives and their pharmaceutical use and compositions |
| JP2014240398A (en) * | 2009-05-20 | 2014-12-25 | セルセウティックス コーポレイション | Nitrile derivatives and their pharmaceutical use and compositions |
| CN102438612B (en) * | 2009-05-20 | 2016-02-03 | 塞尔休迪克斯公司 | Carbonitrile derivatives and pharmaceutical use thereof and compositions |
| US9340491B2 (en) | 2009-05-20 | 2016-05-17 | Cellceutix Corporation | Nitrile derivatives and their pharmaceutical use and compositions |
| EA024038B1 (en) * | 2009-05-20 | 2016-08-31 | Селлсьютикс Корпорейшн | Nitrile derivatives, their pharmaceutical use and use in compositions |
| EA024038B9 (en) * | 2009-05-20 | 2016-10-31 | Селлсьютикс Корпорейшн | Nitrile derivatives, their pharmaceutical use and use in compositions |
| US9610275B2 (en) | 2009-05-20 | 2017-04-04 | Cellceutix Corporation | Nitrile derivatives and their pharmaceutical use and compositions |
| CN113967207A (en) * | 2021-11-22 | 2022-01-25 | 重庆医科大学 | Use of 4-isothioureidobutyronitrile hydrochloride for treating mycobacterial infections |
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| Publication number | Publication date |
|---|---|
| CN101550098B (en) | 2014-07-09 |
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Granted publication date: 20140709 Termination date: 20190114 |