Heteroaromatic pentacyclic compound and medicinal use thereof

A technology of heteroaromatic rings and compounds, applied in the field of new 5-membered heteroaromatic ring compounds, which can solve the problems of no description, no disclosure, etc.

Inactive Publication Date: 2006-05-31
JAPAN TOBACCO INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the basic feature of the compound of this publication is that the nitrogen atom or carbonyl group on the substituent A should be adjacent to the 2-position carbon atom of thiazole or oxazole, or A is an alkylene group; the bond between A and the benzene ring is required; the substituent R 6 The nitrogen atom, oxygen atom, sulfur atom or carbonyl group on

Method used

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  • Heteroaromatic pentacyclic compound and medicinal use thereof
  • Heteroaromatic pentacyclic compound and medicinal use thereof
  • Heteroaromatic pentacyclic compound and medicinal use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-1

[1702] 5-{4-[4-({[4-(1-Ethylpropyl)phenyl]isopropylamino}methyl)-phenyl]thiazol-2-ylmethoxy}nicotinic acid

[1703] (1) 4-(2-(Benzoyloxymethyl)thiazol-4-yl)benzoic acid

[1704]

[1705] To a solution of 4-(bromoacetyl)benzoic acid (10 g, 41.14 mmol) in N,N-dimethylformamide (40 ml) was added 2-(benzoyloxy)ethylthioamide ( 8.03g, 41.14mmol), and the mixture was stirred at room temperature for 1.5 hours. After completing the reaction, sodium bicarbonate (3.46 g, 41.14 mmol) and water were added under ice-cooling, the mixture was stirred at room temperature for 0.5 hour, and the precipitate was collected by filtration. The obtained solid was reduced under reduced pressure to provide the title compound (13.089 g, 93.3%).

[1706] (2) (4-(4-hydroxymethylphenyl)thiazol-2-yl)methyl benzoate

[1707]

[1708] To 4-(2-(benzoyloxymethyl)thiazol-4-yl)benzoic acid (0.5g, 1.47mmol) obtained in Example 1-1(1) in tetrahydrofuran (5ml) at room temperature 1,1'-Carbondiimidazole (0....

Embodiment 1-2 to 1-186

[1727] In the same manner as in Example 1-1, using other conventional methods when necessary, the compounds of Examples 1-2 to 1-186 were produced. Structural formulas and property values ​​of the obtained compounds and those in Example 1-1 are shown in the following table.

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Embodiment 2-1

[1782] {Benzyl-[4-(4-{methyl[4-(1-propylbutyl)benzyl]amino}-phenyl)oxazol-2-ylmethyl]amino}acetic acid

[1783] (1) 4-(1-Propylbutyl)benzaldehyde

[1784]

[1785] To a solution of titanium tetrachloride (18.7ml, 170mmol) in chloroform (50ml) was added dropwise (1-propylbutyl)benzene (10.0g, 56.7mmol) and dichloromethyl methyl ether (7.70mmol) under ice-cooling. ml, 85.1 mmol) in chloroform (40 ml), and the mixture was stirred at the same temperature for 1 hour. The reaction mixture was poured into ice (100 g) and the mixture was stirred at room temperature for 1 hour. The organic layer was successively washed with water, 0.5N aqueous sodium hydroxide solution, water and saturated brine, and dried over magnesium sulfate. After filtration, the solvent was removed and the residue was purified by silica gel column chromatography (eluent; ethyl acetate-hexane 1:50) to provide the title compound (10.0 g, yield 87%).

[1786] (2) N-methyl-4-(1-propylbutyl)benzylamine hydrochlo...

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Abstract

The present invention discloses 5-membered heteroaryl ring compounds represented by formula [I], their prodrugs and pharmaceutically acceptable salts thereof, wherein V is CH or N; W is S or O; R1 and R2 are each H, etc.; X is -N(R4)-, -O-, -S-, -SO2-N(R5)-, -CO-N(R7)-, etc.; L is (see formula I, see formula II), where R20, R21 , R22 and R25 are each H, etc.; E is aryl or heteroaryl ring group; R is -COOH, etc.; B is aryl, etc.; R3 is H, etc.; Y is -C(R13)(R14)-N( R12)-, -C(R13)(R14)-O-, -N(R11)-, -O-, etc.; A is an alkylene group; and Z is an aryl group, etc. Compound [I] has superior protein tyrosine phosphatase 1B inhibitory activity and is useful as a therapeutic agent for diabetes, diabetic complications, hyperlipidemia, obesity and the like.

Description

technical field [0001] The present invention relates to novel 5-membered heteroaryl ring compounds. More specifically, the present invention relates to 5-membered heteroaromatic compounds having protein tyrosine phosphatase 1B (PTP1B) inhibitory activity, pharmaceutically acceptable salts thereof, and pharmaceutical compositions containing them. Background of the invention [0002] Diabetes leads to various metabolic disorders that are primarily characterized by a state of prolonged high blood sugar levels. It shows a wide range of symptoms based on high blood sugar levels, such as dry mouth, polydipsia, polyuria, weight loss, etc. When the state of this high blood sugar level continues for a long time, it is known to cause various complications such as retinopathy, nephropathy, neuropathy, myocardial infarction and cerebral infarction based on arteriosclerosis, and the like. [0003] Diabetes is generally divided into four types: type I diabetes (IDDM; insulin-dependent d...

Claims

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Application Information

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IPC IPC(8): C07D263/32C07D333/16C07D333/18C07D333/20C07D333/38C07D409/12C07D413/12C07D417/06C07D417/14
Inventor 池本知之田中正浩油纳健夫坂本丞平中西博行中川祐一太田毅坂田昌平森长寿代
Owner JAPAN TOBACCO INC
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