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Crystal form of glucopyranose derivative

A technology of crystal forms and compounds, which is applied in the field of preparation of drugs as sodium-dependent glucose transporter inhibitors, can solve the problems that the crystallization behavior and results of organic pharmaceutical compounds cannot be predicted, and the structure and properties of crystal forms cannot be predicted.

Active Publication Date: 2017-05-17
YICHANG HEC CHANGJIANG PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, based on the molecular structure alone, it is usually impossible to predict the crystallization behavior and results of a specific organic pharmaceutical compound (the compound itself or in the form of a salt), let alone predict the structure and properties of the crystal form itself. A large number of experimental explorations are required to obtain beneficial results.

Method used

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  • Crystal form of glucopyranose derivative
  • Crystal form of glucopyranose derivative
  • Crystal form of glucopyranose derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0170] Example 1 Amorphous (1R,2S,3S,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1- Preparation of [(1R)-1-hydroxyethyl]-6,8-dioxobicyclo[3.2.1]octane-2,3,4-triol (compound I)

[0171]

[0172]

[0173] The synthetic route of compound (I) is shown above, wherein compound [(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4 For the preparation method of -ethoxyphenyl)methyl]phenyl]-6,8-dioxobicyclo[3.2.1]octane-1-carbaldehyde (I-1), refer to the preparation method described in the patent WO2015043511, and in which The relevant contents of the above are incorporated into the present invention in their entirety.

[0174] Step 1 (1R)-1-[(1R,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5-[4-chloro-3-[(4-ethoxyphenyl) Methyl]phenyl]-6,8-dioxabicyclo[3.2.1]octane-1-yl]ethanol (I-m)

[0175] At room temperature, the chiral ligand Cr-Salen (11.0 g, 17.4 mmol, 0.15 eq) was added to [(1S,2S,3S,4R,5S)-2,3,4-tribenzyloxy-5- [4-Chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-6,8-diox...

Embodiment 2

[0183] 1. Preparation of Form A

[0184] At room temperature, (1R,2S,3S,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-[(1R)- 1-Hydroxyethyl]-6,8-dioxobicyclo[3.2.1]octane-2,3,4-triol (I) (1.00 g, 2.22 mmol) was dissolved in methanol (2 mL) while stirring While adding water (4 mL) to the solution, during the dropwise addition, the solution gradually changed from colorless and clear to white emulsion. After the dropwise addition, the resulting mixed system was stirred at room temperature for 2 hours, filtered with suction, and the filter cake was vacuum-dried at 50°C to constant weight (vacuum degree -0.098Mpa) to obtain a white solid. The solid was placed in an environment with a relative humidity higher than 60% to obtain crystal A (white solid, 0.96 g, yield 96%).

[0185] 2. Identification of Form A

[0186] (1) X-ray powder diffraction (XRPD) analysis

[0187] The X-ray powder diffraction (XRPD) pattern of crystal form A is as follows figure 1 As shown, the sp...

Embodiment 3

[0198] 1. Preparation of Form B

[0199] At room temperature, (1R,2S,3S,4R,5S)-5-[4-chloro-3-[(4-ethoxyphenyl)methyl]phenyl]-1-[(1R)- 1-Hydroxyethyl]-6,8-dioxobicyclo[3.2.1]octane-2,3,4-triol (I) (1.00 g, 2.22 mmol) was dissolved in methanol (2 mL) while stirring While adding water (4 mL) dropwise into the solution, the solution gradually changed from colorless and clear to white emulsion during the dropwise addition. After the dropwise addition, the resulting mixed system was stirred at room temperature for 2 hours, filtered with suction, and the filter cake was vacuum-dried at 50°C to constant weight (vacuum degree -0.098Mpa) to obtain a white solid. The solid was placed in an environment with a relative humidity lower than 40%, and crystal B (white solid, 0.96 g, yield 96%) was obtained.

[0200] 2. Identification of Form B

[0201] (1) X-ray powder diffraction (XRPD) analysis

[0202] The X-ray powder diffraction (XRPD) pattern of crystal form B is as follows Figure ...

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Abstract

The invention relates to a crystal form of a glucopyranose derivative serving as a sodium-glucose co-transporter (SGLT) inhibitor, a preparation method thereof and a pharmaceutical application thereof, and also relates to a medicine compound containing the crystal form and the application thereof for preparing drugs for treating diabetes and / or diseases related to diabetes.

Description

technical field [0001] The present invention relates to crystalline forms of glucopyranosyl derivatives and pharmaceutical compositions comprising the compounds of the crystalline forms of the present invention, and their use for the preparation of medicaments as sodium-dependent glucose transporter (SGLT) inhibitors. Background technique [0002] Diabetes mellitus is a common chronic disease characterized by hyperglycemia. The occurrence of diabetes is accompanied by insulin resistance in peripheral tissues, decreased insulin secretion in vivo, and increased hepatic gluconeogenesis. When the disease cannot be effectively controlled by diet and exercise, additional insulin or oral hypoglycemic drugs are required for treatment. Current hypoglycemic drugs include biguanides, sulfonylureas, insulin sensitizers, glinides, α-glucosidase inhibitors, and DPP-IV inhibitors. However, these hypoglycemic drugs are currently lacking. Biguanides can cause lactic acidosis, sulfonylureas ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H9/04C07H1/00C07H1/06A61K31/7048A61P3/10A61P27/02A61P25/00A61P13/12A61P5/50A61P3/06A61P3/04A61P9/10A61P9/12
CPCC07B2200/13C07H1/00C07H1/06C07H9/04
Inventor 顾峥伍武勇曲桐张宗远邓炳初
Owner YICHANG HEC CHANGJIANG PHARMA CO LTD
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