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SALTS OF OMARIGLIPTIN

IP.com Disclosure Number: IPCOM000250353D
Publication Date: 2017-Jul-05
Document File: 28 page(s) / 3M

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.

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

Reported herein is an oxalate 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 4.8, 4.7, 4.3, 4.2, and 4.0 Å, and further characterized by additional peaks at d-spacings at about 6.2, 4.4, 4.0, 3.6, and 3.4 Å.  The crystalline Form 1 is also characterized by DSC thermogram having endothermic peaks at about 101.2°C and 170.7°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 crystalline Form 1.

Table 1

d-spacing (Å)


Position (±0.2° 2θ)

Relative Intensity (%)

14.5

6.1

9.8

8.3

10.6

5.2

7.9

11.2

11.4

7.3

12.1

4.2

6.2

14.3

15.8

5.9

15.1

11.7

5.7

15.5

10.9

5.5

16.2

8.3

5.2

17.0

5.5

4.8

18.6

29.6

4.7

18.9

28.2

4.5

19.7

12.4

4.4

20.3

19.1

4.3

20.7

28.6

4.2

21.2

21.7

4.0

22.0

100.0

4.0

22.5

20.1

3.8

23.6

15.2

3.6

24.5

16.9

3.4

25.9

14.7

3.4

26.5

18.4

3.2

28.1

6.5

3.1

28.8

10.6

3.0

29.4

11.0

2.9

30.7

11.3

2.9

31.2

12.2

2.7

33.0

5.5

2.6

34.3

4.7

2.5

35.5

3.7

Also reported herein is an oxalate 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 4.9, 4.6, 4.3 and 3.7 Å, and further characterized by additional peaks at d-spacings at about 5.0, 4.5, 4.4, and 4.2 Å.  The crystalline Form 2 is also characterized by a DSC thermogram having an endothermic peak at about 194.8°C.  The crystalline Form 2 is also characterized by an XRPD pattern substantially as depicted in Figure 4, a DSC thermogram substantially as depicted in Figure 5, or an IR absorption spectrum substantially as depic...