Crystalline polymorphic forms of an antidiabetic compound

Patent metadata

Field	Value
Publication number	US-9272999-B2
Application number	US-201514669303-A
Country	US
Kind code	B2
Filing date	Mar 26, 2015
Priority date	Jan 12, 2009
Publication date	Mar 1, 2016
Grant date	Mar 1, 2016

Abstract

The present invention relates to polymorphic forms of a compound of formula A:

This compound is useful as a glucagon receptor antagonist and serves as a pharmaceutically active ingredient for the treatment of type 2 diabetes and related conditions, such as hyperglycemia, obesity, dyslipidemia, and the metabolic syndrome. Hydrates, hemihydrates, anhydrates and similar polymorphic forms are included.

First claim

What is claimed is:

1. A crystalline polymorphic form of a compound of formula A:

or a pharmaceutically acceptable salt thereof, selected from the group consisting of a free acid hydrate of polymorphic Form I and an anhydrous free acid of polymorphic Form I.

2. A crystalline polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with claim 1 in the form of a free acid hydrate of polymorphic Form I.

3. A crystalline polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with claim 1 in the form of a free acid hydrate having at least three X ray powder diffraction pattern d-spacings consistent with Table 2:

TABLE 2

2θ(2 theta) (degrees)
d-spacing (Å)

7.5
11.74

8.8
10.10

11.3
7.84

13.7
6.44

14.9
5.95

15.4
5.74

17.6
5.05

18.4
4.83

20.3
4.37

21.3
4.17

23.4
3.81

25.6
3.48.

4. A crystalline polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with claim 3 in the form of a free acid hydrate having at least five X ray powder diffraction pattern d-spacings consistent with Table 2:

TABLE 2

2θ(2 theta) (degrees)
d-spacing (Å)

7.5
11.74

8.8
10.10

11.3
7.84

13.7
6.44

14.9
5.95

15.4
5.74

17.6
5.05

18.4
4.83

20.3
4.37

21.3
4.17

23.4
3.81

25.6
3.48.

5. A crystalline polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with claim 1 in the form of a free acid hydrate having at least three C13 solid state NMR characteristic signals with chemical shift values selected from the group consisting of: 11.3, 20.2, 23.9, 33.1, 45.5, 108.6, 118.7, 131.7, 139.3, 148.5, 170.1 and 179.9 ppm.

6. A crystalline polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with claim 1 in the form of an anhydrous free acid.

7. A crystalline polymorphic compound or a pharmaceutically acceptable salt thereof in accordance with claim 1 in the form of an anhydrous free acid having at least three X ray powder diffraction pattern d spacings in accordance with Table 3:

TABLE 3

X-ray powder diffraction: anhydrous free

acid polymorphic Form I of Compound A

2θ(2 theta) (degrees)
d-spacing (Å)

7.8
11.35

8.7
10.19

9.7
9.11

11.3
7.82

11.9
7.41

14.9
5.93

15.7
5.63

17.4
5.10

20.1
4.41

21.7
4.10

25.6
3.47.

Assignees

• Merck Sharp & Dohme

Inventors

• Chung John Y L
• Zhang Yanfeng
• Cote Aaron S
• Scott Jeremy
• Vaynshteyn Yekaterina

Classifications

• C07D209/18 Primary

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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title