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Hetero ring-fused imidazole derivative having ampk activating effect

A compound and heterocyclic group technology, applied in the field of heterocyclic fused imidazole derivatives with AMPK activation, can solve the problem that AMPK activation is not documented

Inactive Publication Date: 2013-07-17
SHIONOGI & CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] However, in Patent Document 5, there is no description about AMPK activation

Method used

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  • Hetero ring-fused imidazole derivative having ampk activating effect
  • Hetero ring-fused imidazole derivative having ampk activating effect
  • Hetero ring-fused imidazole derivative having ampk activating effect

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[1160] 【chemical 70】

[1161]

[1162] While stirring a suspension of 6-chloro-3-nitropyridin-2-amine 1 (20 g, 115 mmol) in absolute ethanol (970 mL), chlorine gas was bubbled at 0°C for 1 hour. Then, stirring the reaction liquid, after bubbling nitrogen gas at room temperature for 1 hour, it stirred at 0 degreeC for 30 minutes. The reaction suspension was collected by filtration and washed with diisopropyl ether, whereby a solid was obtained. The solvent of the obtained filtrate was distilled off under reduced pressure, and the precipitated solid was collected by filtration and washed with diisopropyl ether to obtain a further solid. Compound 2 (18.1 g, 76%) was obtained as a yellow solid by combining the above two solids collected by filtration.

[1163] Compound 2; 1 H-NMR (DMSO-d 6 ) δ: 8.33 (brs, 2H), 8.59 (s, 1H).

[1164] Add iron (48.6 g, 870 mmol) and ammonium chloride (46.5 g, 870 mmol) to compound 2 (36.2 g, 174 mmol) in ethanol (775 mL), water (310 mL) and st...

Embodiment 2

[1180] 【Chemical 71】

[1181]

[1182] Compound A-2; 1 H-NMR (DMSO-d 6 ) δ: 2.56 (s, 3H), 3.84 (s, 3H), 6.51 (d, J = 4.0 Hz, 1H), 7.38-7.45 (m, 3H), 7.49-7.51 (m, 2H), 7.82 (s , 2H), 7.96 (s, 1H).

Embodiment 3

[1184] 【Chemical 72】

[1185]

[1186] Add 4-morpholinophenylboronic acid (2.75 g, 13.29 mmol), PdCl 2 (PPh 3 ) 2 (467 mg, 0.67 mmol), potassium carbonate aqueous solution (2 M, 16.6 ml, 33.23 mmol), stirred at 130°C for 15 minutes under microwave irradiation. Water and ethyl acetate were added to the reaction suspension for extraction, and the organic layer was washed with water and saturated brine, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was purified by silica gel column chromatography to obtain Compound 9 (5.51 g, 93%) as a yellow solid.

[1187] Compound 9; 1 H-NMR (DMSO-d 6) δ: 0.00 (s, 9H), 0.97 (t, J = 8.0 Hz, 2H), 3.32 (t, J = 4.8 Hz, 4H), 3.74 (t, J = 8.0 Hz, 2H), 3.88 (t, J = 4.8 Hz, 4H), 5.75 (s, 2H), 7.15 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 8.45 (s, 1H) , 8.78 (s, 1H).

[1188] TMEDA (4.8 ml, 31.70 mmol) was added to compound 9 (4.7 g, 10.56 mmol) in anhydrous THF (47 mL), and a ...

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PUM

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Abstract

Provided is a compound useful as an AMPK activator. A compound represented by formula (I), a pharmaceutically acceptable salt thereof or a solvate of the same. In formula (I), the moiety represented by (II) is (III); R1s independently represent halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl or the like; m is an integer of 0-3; R2 represents hydrogen or substituted or unsubstituted alkyl; X represents -O-; and Y represents substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl.

Description

technical field [0001] The present invention relates to a compound having an activity of activating adenosine monophosphate-activated protein kinase (hereinafter referred to as AMPK) and useful as a medicine. Background technique [0002] AMPK is a serine-threonine kinase activated by AMP, and has three subunits α, β, and γ, and multiple subtypes (α1, α2, β1, β2, γ1, γ2, γ3) exist in each subunit. [0003] As an energy sensor in the body, AMPK is involved in various physiological functions such as inhibition of gluconeogenesis in the liver, inhibition of fatty acid synthesis, sugar intake in skeletal muscle, and hyperoxidation of fatty acids, and has attracted attention as a target molecule for diabetes therapeutics. attention. Therefore, AMPK activators are expected to be effective in the treatment of diabetes as insulin resistance-improving drugs having insulin-independent blood sugar lowering and lipid-improving effects (Non-Patent Document 1). [0004] Patent Documents...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D471/04A61K31/4188A61K31/437A61K31/52A61K31/5377A61P3/04A61P3/06A61P3/10A61P9/12A61P43/00C07D473/00C07D495/04
CPCC07D495/04C07D473/30C07D491/08C07D473/00C07D491/048C07D513/04C07D471/04C07D473/06C07D473/28C07D487/04A61P3/00A61P3/04A61P3/06A61P3/10A61P9/12A61P43/00C07D519/00A61K31/437A61K31/4188
Inventor 殿垣圭介井埜章児岛荣一加藤学岩津理史田中伸幸藤冈正彦
Owner SHIONOGI & CO LTD
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