Phenyl C-glucoside derivative containing deoxyglucose structure as well as preparation method and application thereof

A -CH2-O-, alkyl technology, applied in the field of diabetes-related drugs, can solve problems such as difficulty in reaching blood sugar control goals, weight gain, etc.

Active Publication Date: 2014-06-18
GUANGZHOU LIXIN PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The antidiabetic drugs currently in clinical use mainly include metformin, sulfonylureas, insulin, thiazolidinediones, α-glucosidase inhibitors and dipeptidyl peptidase-IV inhibitors. It has a good therapeutic effect, but there are safety problems in long-term treatment, such as: liver toxicity, some drugs still have weight gain and many other problems
Moreover, in many cases, it is difficult to achieve the ideal blood sugar control target with timely combination of drugs.

Method used

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  • Phenyl C-glucoside derivative containing deoxyglucose structure as well as preparation method and application thereof
  • Phenyl C-glucoside derivative containing deoxyglucose structure as well as preparation method and application thereof
  • Phenyl C-glucoside derivative containing deoxyglucose structure as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0144] Preparation of (1S)-1-[4-chloro-3-(4-ethoxybenzyl)phenyl]-1,6-dideoxy-D-glucose (I-D1-6)

[0145]

[0146]

[0147] a.

[0148] 4.09g (10mmol) of compound 1 was dissolved in 30mL of dry DMF, stirred under cooling in an ice-water bath, 2.72g (40mmol) of imidazole was added, and then 1.66g (11mmol) of TBDMSCl (tert-butyl dimethyl silicon chloride). After the addition was complete, the reaction mixture was stirred for an additional 3 hours at room temperature. The reaction mixture was diluted with 150 mL of dichloromethane, washed with 50 mL×3 saturated brine, and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, the solvent was evaporated from the filtrate on a rotary evaporator, and the obtained residue was subjected to silica gel column chromatography to obtain pure product 2 as a white foamy solid. 1 H NMR (DMSO-d 6 ,400MHz),δ7.35(d,1H,J=8.0Hz),7.28(d,1H,J=2.0Hz),7.17(dd,1H,J=2.0Hz and8.4Hz),7.05(d,2H ,J=8.8Hz),6.79(d,2H,J=8.8Hz),...

Embodiment 2

[0160] Preparation of (1S)-1-[4-chloro-3-(4-ethoxybenzyl)phenyl]-1,4-dideoxy-D-glucose (I-D1-4)

[0161]

[0162] a.

[0163] 4.09 g (10 mmol) of compound 1, 1.83 g (12 mmol) of benzaldehyde dimethyl acetal and 0.1 g of CAS (camphorsulfonic acid) were dissolved in 30 mL of dry DMF, and heated and stirred at 110° C. for 3 hours under a nitrogen atmosphere. After cooling, the reaction mixture was diluted with 150 mL of dichloromethane, washed successively with 20 mL of 5% sodium carbonate solution and saturated brine, and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, the solvent was evaporated from the filtrate on a rotary evaporator, and the obtained residue was subjected to silica gel column chromatography to obtain pure product 7 as a white solid. Melting point 176-178°C. 1 H NMR (DMSO-d 6 ,400MHz),δ7.45-7.47(m,2H),7.36-7.40(m,4H),7.28(d,1H,J=1.6Hz),7.21(dd,1H,J=2.0Hz and8.4Hz) ,7.08(d,2H,J=8.8Hz),6.83(d,2H,J=8.4Hz),5.60(s,1H),5.31(d,1H,...

Embodiment 3

[0177] Preparation of (1S)-1-[4-chloro-3-(4-ethoxybenzyl)phenyl]-1,3-dideoxy-D-glucose (I-D1-3)

[0178]

[0179] a.

[0180] 4.97g (10mmol) of compound 7 was dissolved in 30mL of dry DMF, stirred in an ice-water bath, 2.72g (40mmol) of imidazole was added, and then 1.66g (11mmol) of TBDMSCl (tert-butyl dimethyl silicon chloride). After the addition was complete, the reaction mixture was stirred for an additional 3 hours at room temperature. The reaction mixture was diluted with 150 mL of dichloromethane, washed with 50 mL×3 saturated brine, and dried over anhydrous sodium sulfate. The desiccant was removed by filtration, the filtrate was evaporated on a rotary evaporator to remove the solvent, and the obtained residue was subjected to silica gel column chromatography to obtain pure product 13 as a white foamy solid. ESI-MS, m / z=628 ([M+NH 4 ] + ).

[0181] b.

[0182] 4.89g (8mmol) of compound 13 was dissolved in 30mL of pyridine, and stirred under cooling in an ice...

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PUM

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Abstract

The invention provides a phenyl C-glucoside derivative (compound as shown in a formula I) containing a deoxyglucose structure and a preparation method thereof, a pharmaceutical composition including the same and application of the phenyl C-glucoside derivative containing a deoxyglucose structure in preparation of medicines for treating diabetes mellitus. The definitions of the substituent groups R1-R7 are as shown in the specification, and the formula I is as shown in the specification.

Description

technical field [0001] The invention relates to the field of medicine related to diabetes. Specifically, the present invention relates to type 2 sodium glucose co-transporter (SGLT2) inhibitors containing phenyl C-glucoside derivatives of deoxyglucose structure and their preparation methods, as well as pharmaceutical combinations containing them, which have a therapeutic effect on diabetes things. Background technique [0002] There are currently about 170 million diabetics in the world, and the vast majority of them are type II (ie, non-insulin-dependent) diabetics. The antidiabetic drugs currently in clinical use mainly include metformin, sulfonylureas, insulin, thiazolidinediones, α-glucosidase inhibitors and dipeptidyl peptidase-IV inhibitors. It has a good therapeutic effect, but there are safety problems in long-term treatment, such as: liver toxicity, some drugs still have weight gain and many other problems. Moreover, in many cases, it is difficult to achieve the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D309/10C07D409/10C07D407/12C07D493/10C07D493/08C07D335/02C07H19/01C07H9/04C07H1/00A61K31/351A61K31/381A61K31/7048A61K31/382A61P3/10
CPCC07D309/10C07D335/02C07D407/12C07D409/10C07D493/08C07D493/10C07H1/00C07H9/04C07H19/01
Inventor 赵桂龙王玉丽魏群超徐为人邹美香汤立达
Owner GUANGZHOU LIXIN PHARM CO LTD
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