Browse Prior Art Database

SALTS OF OMARIGLIPTIN

IP.com Disclosure Number: IPCOM000250342D
Publication Date: 2017-Jun-30
Document File: 26 page(s) / 2M

Publishing Venue

The IP.com Prior Art Database

Abstract

The present disclosure provides salts of omarigliptin, processes for their preparation, pharmaceutical compositions comprising these salts, and their use for the treatment of diabetes mellitus.

This text was extracted from a Microsoft Word document.
At least one non-text object (such as an image or picture) has been suppressed.
This is the abbreviated version, containing approximately 19% of the total text.

SALTS OF OMARIGLIPTIN

Abstract

The present disclosure provides salts of omarigliptin, processes for their preparation, pharmaceutical compositions comprising these salts, and their use for the treatment of diabetes mellitus. 

________________________________________________________________________

Omarigliptin, is chemically (2R,3S,5R)-2-(2,5-difluorophenyl)-5-[2-(methylsulfonyl)-2,6-dihydropyrrolo[3,4-c]pyrazol-5(4H)-yl]tetrahydro-2H-pyran-3-amine, represented by Formula I.

Formula I

Omarigliptin is a dipeptidyl peptidase-IV inhibitor being developed for the treatment of diabetes mellitus.

Reported herein are salts of omarigliptin, processes for their preparation, pharmaceutical compositions comprising these salts, and their use for the treatment of diabetes mellitus. 

The term “about,” as used herein, refers to any value which lies within the range defined by a number up to ±10% of the value.

The term “room temperature,” as used herein, refers to the temperature in the range of 25°C to 35°C.

Reported herein are salts of omarigliptin. Specifically disclosed are trifluoroacetate, fumarate, malate, citrate, maleate, oxalate, benzoate, tartrate, phosphate, or L-pyroglutamate salts of omarigliptin. These salts of omarigliptin are in a crystalline form or in an amorphous form.

A trifluoroacetate salt of omarigliptin is disclosed herein as crystalline Form 1.  The crystalline Form 1 is characterized by an XRPD pattern having peaks at d-spacing’s at about 5.0, 4.5, 4.3, and 4.1 Å, and further characterized by additional peaks at d-spacing’s at about 4.4, 3.8, 3.3, 3.1, and 3.0 Å. The crystalline Form 1 is also characterized by a differential scanning calorimetry (DSC) thermogram having an endothermic peak at about 112.2°C and an exothermic peak at about 154.7°C. The crystalline Form 1 is also characterized by an XRPD pattern substantially as depicted in Figure 1, a DSC thermogram substantially as depicted in Figure 2, or an IR absorption spectrum substantially as depicted in Figure 3. Table-1 provides the d-spacing values (Å), the corresponding 2θ values, and the relative intensity of the crystalline Form 1.

Table 1


d-spacing (Å)

Position (±0.2° 2θ)

Relative Intensity (%)

19.1

4.6

1.5

9.9

8.9

4.1

9.1

9.7

2.0

8.6

10.2

3.5

8.2

10.7

1.5

6.9

12.9

3.6

6.6

13.5

8.5

6.4

13.9

7.7

5.0

17.8

40.5

4.8

18.7

18.2

4.5

19.6

38.3

4.4

20.1

23.4

4.3

20.5

46.0

4.3

20.8

100.0

4.1

21.8

47.9

3.9

22.7

4.8

3.8

23.4

19.6

3.7

24.0

8.8

3.5

25.2

7.1

3.4

26.1

10.7

3.3

26.8

21.2

3.2

27.5

11.1

3.2

27.9

12.3

3.2

28.2

15.2

3.1

28.9

30.5

3.0

29.4

30.9

2.9

31.1

16.0

2.8

31.9

15.3

2.7

32.8

12.5

2.6

33.9

8.5

2.6

34.6

8.1

2.5

35.4

10.9

2.5

35.9

10.0

2.4

37.1

11.6

2.4

37.9

11.5

2.3

38.9

11.1

A trifluoroacetate salt of omarigliptin designated as crystalline Form 2 is also disclosed.  The crystalline Form 2 is characterized by an XRPD pattern having peaks at d-spacings at about 5.9, 4.6, 4.3, and 3.7 Å, and further characterized by additional peaks at d-spacin...