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Quinoline compound for combined treatment of chondrosarcoma

A technology of chondrosarcoma and compounds, applied in the field of pharmaceutical preparations and medicine, can solve the problems of insensitivity, poor lymphatic circulation, and no chemotherapy regimen for chondrosarcoma

Pending Publication Date: 2020-10-27
CHIA TAI TIANQING PHARMA GRP CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, chondrosarcoma has poor blood supply and lymphatic circulation, and is not sensitive to traditional chemotherapy drugs.
Therefore, until now, there is still no effective chemotherapy regimen for the treatment of chondrosarcoma

Method used

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  • Quinoline compound for combined treatment of chondrosarcoma
  • Quinoline compound for combined treatment of chondrosarcoma
  • Quinoline compound for combined treatment of chondrosarcoma

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 11

[0058] Example 1 1-[[[4-(4-Fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl]oxy]methyl] Cyclopropylamine dihydrochloride

[0059]

[0060] 1-[[[4-(4-Fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl was prepared with reference to the method of Example 24 in WO2008112407 ]oxy]methyl]cyclopropylamine, and then according to the preparation method of "Example in salt form" in the specification of WO2008112407, the title compound was prepared.

[0061] Or prepared by referring to the method disclosed in Chinese patent application CN102344438A.

Embodiment 21

[0062] Example 2 1-[[[4-(4-Fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl]oxy]methyl] Preparation of capsules of cyclopropylamine dihydrochloride (dihydrochloride of compound I)

[0063]

[0064] Pulverize the dihydrochloride of compound I, pass through an 80 mesh sieve; then mix with mannitol and hydroxypropyl cellulose; then add the microcrystalline cellulose of the recipe quantity, mix well, pass through a 0.8mm sieve; finally add the recipe quantity of magnesium stearate, mix well and fill the capsules.

[0065] For capsules with other contents of the dihydrochloride of compound I, it can be prepared with reference to the same proportion and prescription above.

Embodiment 3

[0066] Example 3 In vitro experiment

[0067] cell line:

[0068] Human chondrosarcoma cell line CAL-78, SW1353 (source: ATCC).

[0069] Tested drugs:

[0070] 1-[[[4-(4-Fluoro-2-methyl-1H-indol-5-yl)oxy-6-methoxyquinolin-7-yl]oxy]methyl]cyclopropylaminedi Hydrochloride (referred to as the dihydrochloride of Compound I); Methotrexate; Cyclophosphamide; Oxaprozin.

[0071] Preparation method:

[0072] All the above samples were dissolved in dimethyl sulfoxide to prepare a 100 mmol / L mother solution, which was stored at -20°C for later use. When used, it was prepared with DMEM serum culture medium to the desired concentration. The dihydrochloride diluent of compound I was mixed with methotrexate, cyclophosphamide, and oxaprozin diluent respectively to determine whether the compound I dihydrochloride had better effect after combination.

[0073] Cell Culture:

[0074] The test cells were cultured in 10% fetal bovine serum and 0.1 g / L streptomycin and penicillin (final conc...

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Abstract

The invention belongs to the field of medicines, and provides a quinoline compound or pharmaceutically acceptable salt thereof for combined treatment of chondrosarcoma. The invention particularly relates to an application of a treatment effective dose of 1-[[[4-(4-fluoro-2-methyl-1H-indole-5-yl) oxy-6-methoxyquinoline-7-yl] oxy] methyl] cyclopropylamine or pharmaceutically acceptable salt thereofand a second treatment agent in preparation of a combined drug for treating the chondrosarcoma.

Description

technical field [0001] The invention belongs to the field of medicine, and belongs to the technical field of pharmaceutical preparations, in particular to a quinoline compound or a pharmaceutically acceptable salt thereof for combined treatment of chondrosarcoma. Background technique [0002] Chondrosarcoma is the second most malignant bone tumor after osteosarcoma. Its etiology is unknown, mainly from chondrocytes or mesenchymal tissue, and originates from any cartilage internalized bone in the body, which may be related to chromosomal abnormalities. Experimental pathology believes that chondrosarcoma is related to virus infection, while marginal cartilage Sarcomas are associated with genetic factors. [0003] Chondrosarcomas can occur in any part of the skeleton of the body, but occur in the long tubular bones, pelvis, femoral pelvis, and humerus. Chondrosarcoma can occur at any age, more common in adults, rare under the age of 30, the incidence gradually increases after...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4709A61K45/06A61P35/00C07D401/12A61K31/5415A61K31/519A61K31/675
CPCA61K31/4709A61K45/06A61P35/00C07D401/12A61K31/5415A61K31/519A61K31/675A61K2300/00
Inventor 湛筱乐屠礼凡杨朝强张喜全王训强
Owner CHIA TAI TIANQING PHARMA GRP CO LTD
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