CN106366080A - Anti-melanoma compound and application thereof - Google Patents
Anti-melanoma compound and application thereof Download PDFInfo
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- CN106366080A CN106366080A CN201510447483.4A CN201510447483A CN106366080A CN 106366080 A CN106366080 A CN 106366080A CN 201510447483 A CN201510447483 A CN 201510447483A CN 106366080 A CN106366080 A CN 106366080A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an anti-melanoma compound. The compound is named as N-(3-(5-(2-amino-5-hydroxypyrimidin-4-yl)-2-tert-butylthiazol-4-yl)-2-fluoro-5-hydroxyphenyl)-2,6-difluoro-4-hydroxybenzenesulfonamide, and the structural formula of the compound is represented by formula I. The compound is extracted from a natural product, and is evaluated by using melanoma cell strains and immunodeficiency SCID mouse tumor transplantation models. In vivo and in vitro tests show that the compound can substantially inhibit growth of all melanoma cell strains, and also can effectively inhibit growth of human derived melanoma cells in mouse bodies. The compound has a safe, highly-efficient and ideal anticancer effect, can be processed to possibly develop novel anti-melanoma treatment medicines, and has important development and application values.
Description
Technical field
The present invention relates to compound and its application, more particularly, to a kind of compound of melanoma and its application, belong to biomedical sector.
Background technology
Melanoma is a kind of main maligna element cell tumour in skin, is a kind of skin carcinoma of mortality rate highest.It is rare one kind in skin carcinoma, but grade malignancy is high, be one of major causes of death of skin carcinoma.In size, the tendency aspect of shape and color (usual pigmentation) and local challenge and metastasis all has difference to malignant melanoma.Its clinical manifestation is nodular type melanoma, spreads type melanoma, freckle type melanoma and special type melanoma.The diffusion of this tumor is rapid, can be dead after the diagnosis several months.In early days, very 5 years cure rates of the shallow disease damage of table can be 100%.Therefore cure rate depends on early diagnosiss, early treatment.
At present, the Therapeutic Method of melanoma is few, has X-ray therapy, chemical medicinal treatment and surgical cut.Currently the only effective Therapeutic Method is the ocal resection when tumor thickness is less than 1 millimeter.Avax technology company of the U.S. announces that the one kind releasing the said firm scientific research personnel development in Australia treats melanomatous ac vaccine, but cure rate is not also high.Chemotherapy is most commonly seen in clinical practice, but there are problems, it is concentrated mainly on following two aspects: 1. current develop and be used for the melanoma medicine of clinic mainly for the patient being mutated with gene b-raf, if the b-raf gene of therefore patient is not mutated, medicine does not just have anticancer therapeutic.2. the medication effective dose of most clinical medicines is high, causes the destruction of body immune system, is not suitable for old melanoma patients.And patient only takes a kind of medicine for a long time, body volume is also easy to produce drug resistance, effect on driving birds is not good.Therefore find a kind of medicine of new melanoma and very urgent using new and old combination therapies scheme, will there is important clinical meaning to the clinical treatment of melanoma.
Content of the invention
In view of this, in order to solve the above problems, a kind of compound with melanoma that the present invention obtains, it is entitled
N- (3- (5- (2-amino-5-hydroxypyrimidin-4-yl) -2-tert-butylthiazol-4-yl) -2-fluoro-5-hydroxyphenyl) -2,6-difluoro-4-hydroxybenzenesulfonamide, molecular formula sees below formula i.
This compound can significantly inhibit the survival of external melanoma, and can effectively suppress the growth of transplantation tumor in mice body, point out it to have important development and application in melanoma clinical treatment and be worth, can attempt being prepared as the medicine of melanoma.
Brief description
In order that the object, technical solutions and advantages of the present invention are clearer, below in conjunction with accompanying drawing, the present invention is described in further detail, wherein:
Fig. 1. the detection to people source melanoma cell strain survival inhibitory action for this compound of variable concentrations.
Fig. 2. the detection to people source Growth of Tumors Transplanted inhibitory action in mice body for this compound.
Specific embodiment
1) compound suppresses the Motility of melanoma cell strain.
Respectively by melanoma cell strain wm858, wm1158 and wm3734 is inoculated on 96 orifice plates with the every hole of 10,000 cell/100ul.Concentration is added within second day to be respectively 2 and 10 μm of compound and the dmso (matched group) of same volume, with using after 48 hoursLuminescence method cell viability detection kit (promega company) quantitative determines the number of each treatment group living cells.Single agents are directly added in the cultured cells containing serum the method, without washed cell, remove culture medium or carry out multistep sample-adding operation.Concretely comprise the following steps: on 96 orifice plates, 100ul culture medium adds 20 μ lReagent simultaneously mixes, and is detected by luminometer in 10 minutes.
Result shows that this compound all can significantly inhibit the survival (Fig. 1) of three kinds of K-1735s in two kinds of concentration of height, and suppression ratio is up to 85% (10 μm).
2) compound suppresses the growth of people source melanoma cell in mice body.
Raise 30 6-8 week Reconstruction in Sever Combined Immunodeciency (scid) mices, 20 ± 2 grams of body weight.By right for 1,000,000 wm858 human melanoma axil subcutaneous vaccination to every mice.After 10 days, etc. tumor length to general 200mm3, it is randomly divided into 3 groups, every group 10.First group is matched group, every other day lumbar injection 100 μ l normal saline；Second group every other day lumbar injection 100 μ l concentration be 2mg/kg body weight compound；Every other day inject the compound that 100 μ l concentration are 5mg/kg body weight for 3rd group.Continuously inject 8 weeks in this way, after 8 weeks, tumor-bearing mice is put to death, take subcutaneous tumor mass, claim knurl weight.Result shows, this compound, under 2mg/kg body weight and two kinds of dosage of 5mg/kg body weight, all can have obvious inhibitory action to the growth of mouse tumor, and agent effect relation is substantially (Fig. 2).
The foregoing is only the preferred embodiments of the present invention, be not limited to the present invention it is clear that those skilled in the art the present invention can be carried out various change and modification without departing from the spirit and scope of the present invention.So, if these modifications of the present invention and modification belong within the scope of the claims in the present invention and its equivalent technologies, then the present invention is also intended to comprise these changes and modification.
Claims (3)
1. there is the compound of structure shown in formula i:
2. purposes in preparation suppression melanoma medicine for the compound shown in claim 1.
3. a kind of suppression melanoma survival compound it is characterised in that: described melanoma medicine is
With the compound described in claim 1 as active component, add the preparation that pharmaceutical carrier is made.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510447483.4A CN106366080A (en) | 2015-07-21 | 2015-07-21 | Anti-melanoma compound and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510447483.4A CN106366080A (en) | 2015-07-21 | 2015-07-21 | Anti-melanoma compound and application thereof |
Publications (1)
| Publication Number | Publication Date |
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| CN106366080A true CN106366080A (en) | 2017-02-01 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN201510447483.4A Pending CN106366080A (en) | 2015-07-21 | 2015-07-21 | Anti-melanoma compound and application thereof |
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| CN (1) | CN106366080A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020125615A1 (en) * | 2018-12-19 | 2020-06-25 | Inventisbio Shanghai Ltd. | C-terminal src kinase inhibitors |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102083312A (en) * | 2008-05-06 | 2011-06-01 | 葛兰素史密丝克莱恩有限责任公司 | Benzene sulfonamide thiazole and oxazole compounds |
| WO2012125981A2 (en) * | 2011-03-17 | 2012-09-20 | Selexagen Therapeutics, Inc. | Raf kinase inhibitors |
-
2015
- 2015-07-21 CN CN201510447483.4A patent/CN106366080A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102083312A (en) * | 2008-05-06 | 2011-06-01 | 葛兰素史密丝克莱恩有限责任公司 | Benzene sulfonamide thiazole and oxazole compounds |
| WO2012125981A2 (en) * | 2011-03-17 | 2012-09-20 | Selexagen Therapeutics, Inc. | Raf kinase inhibitors |
Non-Patent Citations (1)
| Title |
|---|
| 王丽君等，: "治疗黑色素瘤新药—Tafinlar.", 《药学研究》 * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020125615A1 (en) * | 2018-12-19 | 2020-06-25 | Inventisbio Shanghai Ltd. | C-terminal src kinase inhibitors |
| CN113166136A (en) * | 2018-12-19 | 2021-07-23 | 益方生物科技(上海)股份有限公司 | C-terminal SRC kinase inhibitors |
| CN113166136B (en) * | 2018-12-19 | 2024-03-01 | 益方生物科技(上海)股份有限公司 | C-terminal SRC kinase inhibitors |
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Application publication date: 20170201 |
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| WD01 | Invention patent application deemed withdrawn after publication |