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SALTS OF OMARIGLIPTIN

IP.com Disclosure Number: IPCOM000250352D
Publication Date: 2017-Jul-05
Document File: 40 page(s) / 4M

Publishing Venue

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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.

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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. 

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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.

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.

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

Reported herein is a maleate salt of omarigliptin designated as crystalline Form 1.  The crystalline Form 1 is characterized by an XRPD pattern having peaks at d-spacings at about 7.8, 5.5, 4.9, and 3.7 Å, and further characterized by additional peaks at d-spacings at about 7.7, 5.8, 4.5, 4.2, and 3.9 Å.  The crystalline Form 1 is also characterized by a DSC thermogram having endothermic peaks at about 67.6°C and 149.8°C, and exothermic peaks at about 201.4°C and 242.5°C.  Further, 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 crystalline Form 1.

Table 1


d-spacing (Å)

Position (±0.2° 2θ)

Relative Intensity (%)

19.3

4.6

0.3

11.8

7.5

4.4

9.9

9.0

5.2

7.8

11.4

34.2

7.7

11.5

28.2

7.3

12.1

11.1

6.5

13.5

7.7

5.8

15.2

28.8

5.5

16.1

100.0

5.1

17.3

3.7

4.9

18.1

60.0

4.9

18.2

45.5

4.5

19.7

26.2

4.4

20.1

18.0

4.3

20.7

21.2

4.2

21.0

29.3

4.1

21.9

10.7

3.9

22.9

27.1

3.8

23.5

22.7

3.7

24.0

30.1

3.6

24.5

18.4

3.5

25.1

15.6

3.4

26.0

12.7

3.3

27.0

11.6

3.3

27.4

21.3

3.2

28.2

11.4

3.1

28.6

12.7

2.9

30.4

9.3

2.8

31.4

25.7

2.8

32.0

18.9

2.8

32.2

15.2

2.7

32.8

6.0

2.7

33.8

5.7

2.6

34.8

8.4

2.5

36.5

7.2

2.4

38.0

8.1

2.3

38.7

6.9

Also provided herein is a maleate salt of omarigliptin designated as crystalline Form 2.  The crystalline Form 2 is characterized by an XRPD pattern having peaks at d-spacings at about 6.7, 5.8, 5.5, 5.2, and 4.9 Å, and further characterized by additional peaks at d-spacings at about 11.5, 6.0, 4.5, and 3.7 Å.  The crystalline Form 2 is also characterized by a DSC thermogram having endothermic peaks at about 69.3°C, 154.1°C, and 178.5°C and an exothermic peak at about 241.9°...