Ertugliflozin co-crystals and process for their preparation

Patent metadata

Field	Value
Publication number	US-10294239-B2
Application number	US-201615576452-A
Country	US
Kind code	B2
Filing date	May 24, 2016
Priority date	May 25, 2015
Publication date	May 21, 2019
Grant date	May 21, 2019

Abstract

The present invention relates to processes for the preparation of an ertugliflozin-L-pyroglutamic acid (1:1) and co-crystal ertugliflozin-L-proline (1:1) co-crystal. The present invention further relates to an ertugliflozin-L-proline (1:2) co-crystal, processes for its preparation, and its use for the treatment of type 2 diabetes mellitus.

First claim

We claim:

1. Ertugliflozin-L-proline (1:2) co-crystal of Formula Ia

2. The ertugliflozin-L-proline (1:2) co-crystal according to claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern as depicted in FIG. 1 .

3. The ertugliflozin-L-proline (1:2) co-crystal according to claim 1 , characterized by an XRPD having interplanar spacing (d) values at about 27.3, 5.8, 4.8, 4.7, and 4.2 Å.

4. The ertugliflozin-L-proline (1:2) co-crystal according to claim 3 , characterized by an XRPD having additional interplanar spacing (d) values at about 13.7, 5.1, 4.4, 3.8, 3.5, and 2.8 Å.

5. The ertugliflozin-L-proline (1:2) co-crystal according to claim 1 , characterized by an XRPD having characteristic peak values at about 3.2, 16.2, 18.4, 18.9, and 21.4±0.2° 2θ.

6. The ertugliflozin-L-proline (1:2) co-crystal according to claim 5 , further characterized by an XRPD having additional characteristic peak values at about 6.5, 17.4, 20.4, 23.5, 25.5, and 31.6±0.2° 2θ.

7. The ertugliflozin-L-proline (1:2) co-crystal according to claim 1 , characterized by a differential scanning calorimetric (DSC) thermogram having endothermic peaks at about 148° C. and 236° C. as depicted in FIG. 2 .

8. The ertugliflozin-L-proline (1:2) co-crystal according to claim 1 , characterized by a thermogravimetric analysis (TGA) thermogram as depicted in FIG. 3 .

9. A process for the preparation of an ertugliflozin-L-proline (1:2) co-crystal of Formula Ia of claim 1 ,

wherein the process comprises contacting ertugliflozin with L-proline in the presence of an anhydrous solvent.

10. A pharmaceutical composition comprising an ertugliflozin-L-proline (1:2) co-crystal of claim 1 and one or more pharmaceutically acceptable carriers, diluents, or excipients.

11. A method of treating type 2 diabetes mellitus, the method comprising administering a therapeutically effective amount of ertugliflozin-L-proline (1:2) co-crystal of claim 1 .

Assignees

• Sun Pharmaceutical Ind Ltd

Inventors

• Santra Ramkinkar
• Bhogala Bala Krishna Reddy
• Khanduri Chandra Has

Classifications

• C07D207/277

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

• C07D207/28

  2-Pyrrolidone-5- carboxylic acids; Functional derivatives thereof, e.g. esters, nitriles · CPC title

• A61K31/401

  Proline; Derivatives thereof, e.g. captopril · CPC title

• C07H1/00

  Processes for the preparation of sugar derivatives · CPC title

• C07H9/04

  Cyclic acetals · CPC title