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Bicyclic nitrogen-containing aromatic heterocyclic amide compound

A technology of compound and composition, applied in the direction of organic chemistry, drug combination, medical preparations containing active ingredients, etc., can solve problems such as the usefulness of cancer treatment without enlightenment

Active Publication Date: 2016-02-03
ASTELLAS PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, there is no description in this document of the compound of the formula (I) of the present invention described below, and there is no specific description suggesting usefulness for the treatment of cancer, etc.

Method used

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  • Bicyclic nitrogen-containing aromatic heterocyclic amide compound
  • Bicyclic nitrogen-containing aromatic heterocyclic amide compound
  • Bicyclic nitrogen-containing aromatic heterocyclic amide compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0338] Hereinafter, the production method of the compound of formula (I) is demonstrated in more detail based on an Example. It should be noted that the present invention is not limited to the compounds described in the following examples. In addition, the production methods of the raw material compounds are shown in the production examples, respectively. In addition, the production method of the compound of formula (I) is not limited to the production method of the specific examples shown below, and the compound of formula (I) can also be obtained by a combination of these production methods, or it will be obvious to those skilled in the art method to manufacture.

[0339] In this specification, naming software such as ACD / Name (registered trademark, Advanced Chemistry Development, Inc.) may be used for naming compounds.

[0340] In addition, the concentration mol / l is expressed as M for the sake of convenience. For example, a 1M aqueous sodium hydroxide solution refers to...

manufacture example 1

[0344]In 5-bromo-1H-benzimidazole-2-carboxylic acid (1.0g), 1-[4-(trifluoromethyl)benzyl]piperazine (1.0g), 1-hydroxybenzotriazole (840mg) and N,N-dimethylformamide (10ml: hereinafter abbreviated as DMF) mixture, add N-[3-(dimethylamino)propyl]-N'-ethylcarbodiimide hydrochloride ( 1.2 g) and stirred overnight at room temperature. Saturated aqueous sodium bicarbonate solution was added to the reaction mixture and stirred at room temperature for 1 hour, and the resulting solid was filtered off and dried under reduced pressure. The obtained solid was dissolved in a mixture of chloroform (100 ml) and ethanol (1 ml) under reflux with heating. The mixture was cooled to room temperature, then hexane (100ml) was added. The resulting solid was filtered off and dried under reduced pressure to give (5-bromo-1H-benzimidazol-2-yl){4-[4-(trifluoromethyl)benzyl]piperazine as a solid -1-yl}methanone (1.4 g).

manufacture example 2

[0346] A mixture of 2-chloroquinoline-6-carboxylic acid (500 mg), thionyl chloride (5 ml) and DMF (1 drop) was heated to reflux for 30 minutes, then allowed to cool to room temperature. To a mixture of the solid obtained by concentrating the reaction mixture under reduced pressure and dichloromethane were added 1-[4-(trifluoromethyl)benzyl]piperazine (620 mg) and triethylamine (340 µl) under ice-cooling , and stirred at room temperature for 2 hours. Saturated aqueous sodium bicarbonate solution was added to the reaction mixture, followed by extraction with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution, and then dried over anhydrous sodium sulfate. The desiccant was removed, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by amino silica gel column chromatography (hexane-ethyl acetate) to obtain (2-chloroquinolin-6-yl){4-[4-(trifluoromethyl)benzyl Base]piperazin-1-yl}methanone (630m...

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PUM

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Abstract

This invention relates to a bicyclic nitrogen-containing aromatic heterocyclic amide compound of formula (I), or a salt thereof, which has excellent Complex 1 inhibitory effect and AMPK activating effect, and which is useful as a therapeutic drug for breast cancer. This compound has a cell growth inhibitory effect on a human PIK3CA mutation-positive breast cancer cell line not expressing MCT4 and on a human breast cancer cell line not expressing MCT4 and not having a PIK3CA mutation, and exhibits antitumor action in human PIK3CA mutation-positive breast cancer cell line MDA-MB-453 cell tumor-bearing mice not expressing MCT4.

Description

technical field [0001] The present invention relates to a bicyclic nitrogen-containing aromatic heterocyclic amide compound useful as an active ingredient of a pharmaceutical composition, for example, a pharmaceutical composition for treating breast cancer. Background technique [0002] Breast cancer is caused by changes in normal cells of the breast due to gene mutations and DNA damage, and disorderly proliferation. It has the highest attack rate among female cancers, and more than 1.3 million people are diagnosed with breast cancer every year in the world, and more than 450,000 people die from breast cancer (CA CancerJClin.2011, 61:69-90). [0003] Treatment of breast cancer is broadly classified into surgery (surgical therapy), anticancer agents (hormone therapy, chemotherapy), and radiation exposure (radiotherapy), and these methods are combined in many cases. From the perspective of gene map analysis, breast cancer is classified as (1) luminal A (hormone receptor (estr...

Claims

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Application Information

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IPC IPC(8): C07D215/48C07D235/30C07D401/04C07D401/12C07D401/14C07D405/14C07D413/14C07D471/04C07D471/14A61K31/496A61K31/497A61P15/14A61P35/00
CPCA61P15/14A61P35/00C07D215/48C07D235/30C07D401/04C07D401/12C07D401/14C07D405/14C07D413/14C07D417/14C07D471/04C07D471/14
Inventor 大贯圭蓟英范泽田由纪进崇史仓本和幸菊池重俊斋藤智之滨口寿雄长岛建之
Owner ASTELLAS PHARMA INC
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