Crystalline forms

Patent metadata

Field	Value
Publication number	US-2019047996-A1
Application number	US-201615759710-A
Country	US
Kind code	A1
Filing date	Sep 14, 2016
Priority date	Sep 15, 2015
Publication date	Feb 14, 2019
Grant date	—

Abstract

The invention relates to a crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid, processes for the preparation thereof, pharmaceutical compositions comprising said crystalline forms, pharmaceutical compositions prepared from such crystalline forms, and their use as a medicament, especially as CRTH 2 receptor modulators.

First claim

1 . A crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid, characterized by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, and 21.1°, wherein the X-ray powder diffraction diagram is measured at about 5%, at about 20%, at about 50%, or at about 95% relative humidity and at a temperature of about 25° C.

2 . A crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid according to claim 1 , characterized by:
a. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 19.8°, 20.0°, 21.1° and 26.4°, wherein the X-ray powder diffraction diagram is measured at about 5% relative humidity and at a temperature of about 25° C.; or b. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 19.7°, 21.1° and 26.4°, wherein the X-ray powder diffraction diagram is measured at about 20% relative humidity and at a temperature of about 25° C.; or c. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 19.5°, 21.1°, 21.4° and 26.1°, wherein the X-ray powder diffraction diagram is measured at about 50% relative humidity and at a temperature of about 25° C.; or d. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 19.5°, 21.1°, 21.5° and 26.0°, wherein the X-ray powder diffraction diagram is measured at about 95% relative humidity and at a temperature of about 25° C.

3 . A crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid according to claim 1 , characterized by:
a. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 15.6°, 19.8°, 20.0°, 21.1°, 23.7°, 26.4°, 27.5° and 28.4°, wherein the X-ray powder diffraction diagram is measured at about 5% relative humidity and at a temperature of about 25° C.; or b. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 15.6°, 19.7°, 21.1°, 23.3°, 23.6°, 26.4°, 27.4°, and 28.4°, wherein the X-ray powder diffraction diagram is measured at about 20% relative humidity and at a temperature of about 25° C.; or c. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 15.2°, 16.1°, 19.5°, 21.1°, 21.4°, 23.0°, 26.1°, and 27.0°, wherein the X-ray powder diffraction diagram is measured at about 50% relative humidity and at a temperature of about 25° C.; or d. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 16.2°, 18.9°, 19.5°, 21.1°, 21.5°, 22.9°, 26.0°, and 27.0°, wherein the X-ray powder diffraction diagram is measured at about 95% relative humidity and at a temperature of about 25° C.

4 . A crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid according to claim 1 ,
a. which essentially shows the X-ray powder diffraction pattern as depicted in FIG. 1 , wherein the X-ray powder diffraction diagram is measured at about 5% relative humidity and at a temperature of about 25° C.; or b. which essentially shows the X-ray powder diffraction pattern as depicted in FIG. 2 , wherein the X-ray powder diffraction diagram is measured at about 20% relative humidity and at a temperature of about 25° C.; or c. which essentially shows the X-ray powder diffraction pattern as depicted in FIG. 3 , wherein the X-ray powder diffraction diagram is measured at about 50% relative humidity and at a temperature of about 25° C.; or d. which essentially shows the X-ray powder diffraction pattern as depicted in FIG. 4 , wherein the X-ray powder diffraction diagram is measured at about 95% relative humidity and at a temperature of about 25° C.

5 . A crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid obtainable by:
a) preparation of a solution of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid in THF at 25 mg/mL; b) dispensing 0.2 mL of the solution in a 4 mL glass vial; c) evaporation of THF by use of an instrument that allows evaporation by combined use of infrared radiation, vortexing and vacuum set at 30° C. and 100 mbar for 30 minutes; d) addition of 0.02 mL of a solvent selected from ethylacetate, acetonitrile, acetone, or isopropanol to the solid residue and allowing to incubate for 3 days at ambient temperature in the closed vial; and e) isolation of the obtained solid residue.

6 . A crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid according to claim 5 , characterized by the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, and 21.1°, wherein the X-ray powder diffraction diagram is measured at about 5%, at about 20%, at about 50%, or at about 95% relative humidity and at a temperature of about 25° C.

7 . A crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid according to claim 5 , characterized by:
a. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 19.8°, 20.0°, 21.1° and 26.4°, wherein the X-ray powder diffraction diagram is measured at about 5% relative humidity and at a temperature of about 25° C.; or b. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 19.7°, 21.1° and 26.4°, wherein the X-ray powder diffraction diagram is measured at about 20% relative humidity and at a temperature of about 25° C.; or c. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 19.5°, 21.1°, 21.4° and 26.1°, wherein the X-ray powder diffraction diagram is measured at about 50% relative humidity and at a temperature of about 25° C.; or d. the presence of peaks in the X-ray powder diffraction diagram at the following angles of refraction 2θ: 12.6°, 14.0°, 19.5°, 21.1°, 21.5° and 26.0°, wherein the X-ray powder diffraction diagram is measured at about 95% relative humidity and at a temperature of about 25° C.

8 . A crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid according to claim 1 , which shows an endothermal event in the range of about 260° C. to 276° C. as determined by differential scanning calorimetry.

9 . A crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid according to claim 1 , which essentially shows a gravimetric moisture sorption profile as depicted in FIG. 5 , wherein the gravimetric moisture sorption profile is measured at 25° C.

10 . A crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid according to claim 1 .

11 . A crystalline form of (S)-2-(8-((5-chloropyrimidin-2-yl)(methyl)amino)-2-fluoro-6,7,8,9-tetrahydro-5H-pyrido[3,2-b]indol-5-yl)acetic acid according to c

Assignees

• Idorsia Pharmaceuticals Ltd

Inventors

• Aissaoui Hamed
• Boss Christoph
• Bouis Patrick
• Hazemann Julien
• Siegrist Romain
• Von Raumer Markus

Classifications

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07B2200/13

  Crystalline forms, e.g. polymorphs · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P11/06

  Antiasthmatics · CPC title