Co-crystals of SGLT2 inhibitors, process for their preparation and pharmaceutical compositions thereof

Patent metadata

Field	Value
Publication number	US-10428053-B2
Application number	US-201615759562-A
Country	US
Kind code	B2
Filing date	Sep 15, 2016
Priority date	Sep 15, 2015
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

The present invention provides solid forms of SGLT2 inhibitors, to processes for their preparation and their use in the purification of SGLT2 inhibitors and also provided pharmaceutical compositions comprising them and their use in therapy.

First claim

The invention claimed is:

1. Co-crystals selected from the group consisting of co-crystals of canagliflozin and DL-pipecolic acid, co-crystals of canagliflozin and L-pipecolic acid, co-crystals of canagliflozin and D-pipecolic acid, co-crystals of dapagliflozin and DL-pipecolic acid, co-crystals of dapagliflozin and D-pipecolic acid, co-crystals of dapagliflozin and L-pipecolic acid, and co-crystals of empagliflozin and DL-pipecolic acid.

2. Co-crystals of canagliflozin and DL-pipecolic acid of claim 1 , wherein the co-crystals are characterized by an X-Ray powder diffraction (XRD) pattern having one or more peaks at about 4.00, 9.12, 9.60, 10.50, 11.34, 14.92, 17.56, 17.92, 18.92, 19.80, 20.18, 20.60, 21.74, 22.20, 22.94, 23.48 and 26.90±0.2° 2θ.

3. A process for the preparation of co-crystals of canagliflozin and a co-crystal former selected from one of the group consisting of DL-pipecolic acid, L-pipecolic acid, D-pipecolic acid, nicotinic acid, pyrazine-2-carboxylic acid, and pyrazole, comprising:
providing a solution or suspension comprising the canagliflozin and co-crystal former in one or more organic solvents; and
isolating the co-crystals.

4. The process of claim 3 , wherein when the co-crystal former is DL-pipecolic acid, the one or more organic solvents is selected from the group consisting of methanol, ethanol, n-butanol, ethyl acetate, isopropyl acetate, hexane, heptane and mixtures thereof.

5. The process of claim 3 , wherein when the co-crystal former is L-pipecolic acid, the one or more organic solvents is selected from the group consisting of ethanol, ethyl acetate, n-heptane, and mixtures thereof.

6. The process of claim 3 , wherein when the co-crystal former is D-pipecolic acid, the one or more organic solvents is selected from the group consisting of ethanol, ethyl acetate, n-heptane, and mixtures thereof.

7. Co-crystals of dapagliflozin and DL-pipecolic acid of claim 1 , wherein the co-crystals are characterized by an X-Ray powder diffraction (XRD) pattern having one or more peaks at about 3.91, 7.83, 8.41, 9.38, 11.76, 15.38, 15.65, 16.26, 16.99, 17.62, 17.95, 18.36, 19.96, 20.28, 21.29, 21.97, 23.02, 23.65, 24.68, 26.72, 30.43 and 31.34 ±0.2° 2θ.

8. A process for the preparation of co-crystals of dapagliflozin and a co-crystal former selected from one of the group consisting of DL-pipecolic acid, D-pipecolic acid, and L-pipecolic acid, comprising:
a) providing a solution or suspension comprising the dapagliflozin and co-crystal former in one or more organic solvents; and
b) isolating the co-crystals.

9. The process of claim 8 , wherein when the co-crystal former is DL-pipecolic acid, the one or more solvents is selected from the group consisting of an ester, an alcohol, water, and mixtures thereof.

10. The process of claim 9 , wherein the one or more solvents is isopropyl acetate.

11. The process of claim 8 , wherein the isolation of step b) is carried out by filtration.

12. Co-crystals of dapagliflozin and D-pipecolic acid of claim 1 , wherein the co-crystals are characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with FIG. 13 .

13. The process of claim 8 , wherein when the co-crystal former is D-pipecolic acid, the one or more solvents is selected from the group consisting of an ester, an alcohol, water, and mixtures thereof.

14. The process of claim 13 , wherein the one or more solvents is isopropyl acetate.

15. The process of claim 13 , wherein the isolation of step b) is carried out by filtration.

16. Co-crystals dapagliflozin and L-pipecolic acid of claim 1 , wherein the co-crystals are characterized by an X-Ray powder diffraction (XRD) pattern substantially in accordance with FIG. 14 .

17. The process of claim 8 , wherein when the co-crystal former is L-pipecolic acid, the one or more solvents is selected from the group consisting of an ester, an alcohol, water, and mixtures thereof.

18. The process of claim 17 , wherein the one or more solvents is isopropyl acetate.

19. The process of claim 17 , wherein the isolation of step b) is carried out by filtration.

20. Co-crystals of empagliflozin DL-pipecolic acid of claim 1 , wherein the co-crystals are characterized by an X-Ray powder diffraction (XRD) pattern having one or more peaks at about 5.5, 9.8, 11.0, 12.0, 12.2, 14.7, 15.8, 16.3, 17.3, 17.7, 18.1, 18.5, 18.9, 19.6, 20.7, 21.1, 22, 22.5, 23.5, 24.5, 25.0, 26.4, 27.2, 28.1, 29, 29.8, 30.9, 31.4, 33.7, 35.3, 36.7, 39.6±0.2° 2θ.

Assignees

• Laurus Labs Ltd

Inventors

• Chivukula Kameswar Rao
• Thaimattam Ram
• Bandlamudi Veeranarayana
• Padala Durga Visweswar Rao
• Gade Narapa Reddy
• Regandla Nageswar Rao
• Yasam Sivarami Reddy
• Moturu Venkata Ramakrishnamurthy
• Indukuri Venkata Sunil Kumar
• Vasireddi Uma Maheswar Rao
• Kalidindi Srihari Raju
• Chava Satyanarayana

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• C07D409/10 Primary

  linked by a carbon chain containing aromatic rings · CPC title

• C07D211/60

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D241/24

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D213/80

  in position 3 · CPC title