Thienopyridine derivative

A compound and substituent technology, applied in the field of compounds that promote bone formation

Inactive Publication Date: 2007-05-23
SANKYO CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, there are no reports of the effects of these compounds on bone

Method used

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Examples

Experimental program
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Effect test

Embodiment 1

[0329] (Example 1) 3-Amino-4-(dimethylamino)thieno[2,3-b]pyridine-2-carboxamide (exemplified compound No. 2-17)

[0330] With reference to the method of Pharm. Chem. J. (Engl. Transl.), 26, (1992), 870-874, it was prepared as follows.

[0331] (1a)(2Z)-2-cyano-3-(dimethylamino)but-2-enethioamide

[0332] 1.00 g (10 mmol) of cyanothioacetamide and 1.73 g (13 mmol) of N,N-dimethylacetamide dimethyl acetal were dissolved in 5 mL of acetonitrile, and stirred at room temperature for 1 hour. The precipitated crystals were collected by filtration, and the crystals were washed with acetonitrile to obtain 1.05 g of the title compound (yield 62%).

[0333] Mp 155-158℃;

[0334] 1 H NMR(DMSO-d 6 , 400MHz) δ 2.27 (3H, s), 3.03 (6H, s), 8.08 (1H, br), 8.83 (1H, br).

[0335] (1b) 4-(Dimethylamino)-2-thio-1,2-dihydropyridine-3-carbonitrile

[0336] 1.05g (6.2mmol) of (2Z)-2-cyano-3-(dimethylamino)but-2-enethioamide prepared in Example 1(1a) and 2.22g (18.6mmol) of N, The N-dimethylformamide dim...

Embodiment 2

[0346] (Example 2) 3-Amino-4-(diethylamino)thieno[2,3-b]pyridine-2-carboxamide (exemplified compound No. 2-33)

[0347] (2a)(2Z)-2-cyano-3-(diethylamino)but-2-enethioamide

[0348] 406 mg (2.38 mmol) (2Z)-2-cyano-3-ethoxybut-2-ene thioamide (J. Org. Chem., (1962), 27, 2433-2439) and 0.36 mL ( 3.53 mmol) diethylamine was suspended in 5 mL of ethanol and stirred at room temperature for 2 hours. The solvent was distilled off, and the resulting residue was purified by silica gel column chromatography (ethyl acetate / hexane=2:1) ​​to obtain 237 mg of the title compound (yield 50%).

[0349] 1 H NMR(CDCl 3 , 400MHz) δ1.32 (6H, t, J = 7.04 Hz), 2.71 (3H, s), 3.65 (4H, q, J = 7.05 Hz), 6.69 (2H; br s).

[0350] (2b) 4-(Diethylamino)-2-thio-1,2-dihydropyridine-3-carbonitrile

[0351] (2Z)-2-cyano-3-(diethylamino)but-2-enethioamide prepared in Example 2(2a) was used instead of (2Z)-2-cyano-3-(dimethyl (Ylamino)but-2-enethioamide was reacted in the same manner as in Example 1(1b) to obtain th...

Embodiment 3

[0360] (Example 3) 3-Amino-4-(dimethylamino)-6-methylthieno[2,3-b]pyridine-2-carboxamide (exemplified compound No. 2-102)

[0361] (3a) 4-(Dimethylamino)-6-methyl-2-thio-1,2-dihydropyridine-3-carbonitrile

[0362]1.46 g (7.5 mmol) 2-chloro-4-(dimethylamino)-6-methylnicotinonitrile (Pharm.Chem.J., (Engl.Transl.), 25, (1991), 623-628 .) and 0.74 g (9.7 mmol) of thiourea were suspended in 25 mL of toluene, and stirred under heating and reflux for 4 hours. 40 mL of ethanol was added to the reaction mixture, and then heated to reflux for 30 minutes. Leave it at room temperature overnight, filter the precipitated solid, and wash with ethanol, water, and ethanol in sequence to obtain 0.64 g of the crude product of the title compound.

[0363] 1 H NMR(DMSO-d 6 , 400MHz) δ 2.20 (3H, s), 3.18 (6H, s), 6.23 (1H, s), 12.41 (1H, br).

[0364] (3b) 3-Amino-4-(dimethylamino)-6-methylthieno[2,3-b]pyridine-2-carboxamide

[0365] 0.19g (1.0mmol) of 4-(dimethylamino)-6-methyl-2-thio-1,2-dihydropyrid...

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Abstract

The invention provides osteogenesis-promoting compounds, namely, compounds represented by the general formula (I) and pharmacologically acceptable salts thereof: wherein R<1> is H or alkyl; R<2> is RS-, RO-, RNH-, R(R)N-, or cyclic amino; and R and R are each optionally substituted alkyl, optionally substituted cycloalkyl, or the like.

Description

Technical field [0001] The present invention relates to compounds that promote bone formation. Background technique [0002] It is known that thienopyridine derivatives have an inhibitory effect on the IκB kinase complex (see Patent Document 1). In addition, 3-amino-4-(dimethylamino)thieno[2,3-b]pyridine-2-carboxamide and 3-amino-4-anilinothieno[2,3-b]pyridine are also known -2-carboxamide is a well-known compound (see Non-Patent Document 1). However, there are no reports on the effects of these compounds on bone. [0003] Patent Document 1: International Publication No. 03 / 103661 Specification [0004] Non-Patent Document 1: Pharm. Chem. J. (Engl. Transl.), 26, 870-874 (1992) Summary of the invention [0005] The present inventors conducted in-depth research on compounds that promote bone formation, and as a result, found that thienopyridine derivatives have excellent pharmacological effects, thereby completing the present invention. [0006] The invention relates to: [0007] ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D495/04A61K31/4365A61K31/4545A61K31/4725A61K31/496A61K31/5377A61K31/541A61K31/55A61K31/551A61K31/553A61K31/554A61P19/02A61P19/08A61P19/10A61P29/00
CPCA61K31/551A61K31/4545A61K31/554A61K31/553A61K31/496A61K31/4365A61K31/5377C07D495/04A61K31/541A61K31/55A61K31/4725A61P19/02A61P19/08A61P19/10A61P29/00
Inventor 大泉喜代志内藤觉中尾彰筱塚刚松井智岛田神生
Owner SANKYO CO LTD
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