Crystalline forms of a somatostatin modulator

Patent metadata

Field	Value
Publication number	US-11773076-B2
Application number	US-202217673579-A
Country	US
Kind code	B2
Filing date	Feb 16, 2022
Priority date	Feb 17, 2021
Publication date	Oct 3, 2023
Grant date	Oct 3, 2023

Abstract

Described herein are crystalline forms of 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide, uses of such crystalline forms in the preparation of pharmaceutical compositions for the treatment of diseases or conditions that would benefit by administration with a somatostatin modulator compound.

First claim

What is claimed is:

1. A crystalline form of 4-[(3S)-3-aminopyrrolidin-1-yl]-6-cyano-5-(3,5-difluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]pyridine-3-carboxamide (Compound 1):
wherein the crystalline form is crystalline Pattern A of Compound 1 characterized as having: an XRPD pattern with peaks at 9.4±0.2° 2-Theta, 12.9±0.2° 2-Theta, 13.3±0.2° 2-Theta, 17.1±0.2° 2-Theta, 18.8±0.2° 2-Theta, 19.3±0.2° 2-Theta, and 20.7±0.2° 2-Theta as measured with Cu Kα1 radiation;
wherein the crystalline form is crystalline Pattern B of Compound 1 characterized as having: an X-Ray Powder Diffraction (XRPD) pattern substantially the same as shown in FIG. 4 as measured with Cu Kα1 radiation;
wherein the crystalline form is crystalline Pattern C of Compound 1 characterized as having an X-Ray Powder Diffraction (XRPD) pattern substantially the same as shown in FIG. 6 as measured with Cu Kα1 radiation; or
wherein the crystalline form is crystalline Pattern D of Compound 1 characterized as having: an X-Ray Powder Diffraction (XRPD) pattern substantially the same as shown in FIG. 7 as measured with Cu Kα1 radiation.

2. The crystalline form of claim 1 , wherein the crystalline form is crystalline Pattern A of Compound 1.

3. The crystalline form of claim 2 , wherein the crystalline Pattern A of Compound 1 is characterized as having:
an X-Ray Powder Diffraction (XRPD) pattern substantially the same as shown in FIG. 1 as measured with Cu Kα1 radiation;
an XRPD pattern with peaks at 9.4±0.2° 2-Theta, 12.9±0.2° 2-Theta, 13.3±0.2° 2-Theta, 17.1±0.2° 2-Theta, 18.8±0.2° 2-Theta, 19.3±0.2° 2-Theta, and 20.7±0.2° 2-Theta as measured with Cu Kα1 radiation;
a Differential Scanning calorimetry (DSC) thermogram substantially the same as shown in: FIG. 2 ; or FIG. 3 ;
a DSC thermogram with:
an endotherm having onset at about 96.5° C. and peak at about 106.0° C.; or
an endotherm having onset at about 86.6° C. and peak at about 101.4° C.;

a Thermogravimetric Analysis (TGA) pattern substantially the same as shown in FIG. 3 ;
a TGA pattern with a w/w loss of about 3.08% from 50 to 145° C.;
reversible water uptake of about 0.7% between 2% and 95% relative humidity;
an unchanged XRPD pattern after Dynamic Vapor Sorption (DVS) analysis between 2% and 95% relative humidity;
an unchanged XRPD pattern after storage at 40° C./75% relative humidity for 7 days;
an unchanged XRPD pattern after DSC analysis with thermal cycling from 30° C. to 118° C.;
an XRPD pattern that converts to amorphous material after DSC analysis with thermal cycling from 30° C. to 150° C.;
unit cell parameters substantially equal to the following at 100 K:

Crystal System
Monoclinic

Space Group
P2 1

a (Å)
10.1810(2)

b (Å)
9.9510(2)

c (Å)
10.7342(2)

α
90°

β
114.6748(5)°

γ
90°

V (Å 3 )
988.20(3)

Z
2

Calculated Density (Mg/m 3 )
1.537

Absorption coefficient (mm −1 )
1.169

F(000)
472

or
combinations thereof.

4. The crystalline form of claim 2 , wherein the crystalline Pattern A of Compound 1 is characterized as having: an X-Ray Powder Diffraction (XRPD) pattern with peaks at 9.4±0.2° 2-Theta, 12.9±0.2° 2-Theta, 13.3±0.2° 2-Theta, 17.1±0.2° 2-Theta, 18.8±0.2° 2-Theta, 19.3±0.2° 2-Theta, and 20.7±0.2° 2-Theta as measured with Cu Kα1 radiation.

5. The crystalline form of claim 2 , wherein the crystalline Pattern A of Compound 1 is characterized as having: an X-Ray Powder Diffraction (XRPD) pattern substantially the same as shown in FIG. 1 as measured with Cu Kα1 radiation.

6. The crystalline form of claim 5 , wherein the crystalline Pattern A of Compound 1 is characterized as having: a Differential Scanning calorimetry (DSC) thermogram substantially the same as shown in FIG. 2 .

7. The crystalline form of claim 4 , wherein the crystalline Pattern A of Compound 1 is characterized as having: a Differential Scanning calorimetry (DSC) thermogram with an endotherm having onset at about 96.5° C. and peak at about 106.0° C.

8. The crystalline form of claim 4 , wherein the crystalline Pattern A of Compound 1 is characterized as having: a Differential Scanning calorimetry (DSC) thermogram with an endotherm having onset at about 86.6° C. and peak at about 101.4° C.

9. The crystalline form of claim 5 , wherein the crystalline Pattern A of Compound 1 is characterized as having: a Differential Scanning calorimetry (DSC) thermogram substantially the same as shown in FIG. 3 .

10. The crystalline form of claim 4 , wherein the crystalline Pattern A of Compound 1 is characterized as having: a Thermogravimetric Analysis (TGA) pattern with a w/w loss of about 3.08% from 50 to 145° C.

11. The crystalline form of claim 5 , wherein the crystalline Pattern A of Compound 1 is characterized as having: a Thermogravimetric Analysis (TGA) pattern substantially the same as shown in FIG. 3 .

12. The crystalline form of claim 4 , wherein the crystalline Pattern A of Compound 1 is characterized as having: reversible water uptake of about 0.7% between 2% and 95% relative humidity.

13. The crystalline form of claim 4 , wherein the crystalline Pattern A of Compound 1 is characterized as having:
an unchanged X-Ray Powder Diffraction (XRPD) pattern after Dynamic Vapor Sorption (DVS) analysis between 2% and 95% relative humidity;
an unchanged XRPD pattern after storage at 40° C./75% relative humidity for 7 days;
an unchanged XRPD pattern after Differential Scanning calorimetry (DSC) analysis with thermal cycling from 30° C. to 118° C.; or
an XRPD pattern that converts to amorphous material after DSC analysis with thermal cycling from 30° C. to 150° C.

14. The crystalline form of claim 2 , wherein the crystalline Pattern A of Compound 1 is characterized as having unit cell parameters substantially equal to the following at 100 K:

Crystal System
Monoclinic

Space Group

Assignees

• Crinetics Pharmaceuticals Inc

Inventors

• Zhao Yuxin
• Reddy Jayachandra P
• Maceachern Lauren
• Kahwaji Samer
• Monyoncho Evans
• Mueller Peter

Classifications

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P3/00

  Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00) · CPC title