Crystalline solid state form of the benzene sulphonic acid salt of 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide

Patent metadata

Field	Value
Publication number	US-9975901-B2
Application number	US-201515515683-A
Country	US
Kind code	B2
Filing date	Sep 30, 2015
Priority date	Oct 2, 2014
Publication date	May 22, 2018
Grant date	May 22, 2018

Abstract

The present invention relates to a salt form of a benzodiazepine derivative, in particular crystalline solid state forms, to pharmaceutical compositions comprising the same and to its use in therapy.

First claim

The invention claimed is:

1. A benzene sulphonic acid salt of 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide in crystalline solid state form.

2. The crystalline solid state form according to claim 1 characterised by an X-ray powder diffraction (XRPD) pattern substantially as shown in FIG. 1 .

3. The crystalline solid state form according to claim 1 characterised by an X-ray powder diffraction pattern comprising at least three diffraction angles, expressed in degrees 2θ, selected from a group consisting of about 5.5, 7.4, 9.1, 10.0, 10.4, 13.3, 13.6, 14.9, 18.7, 20.4, 20.9, 22.8 and 23.1° (±0.1°).

4. The crystalline solid state form according to claim 1 characterised by a 13 C SSNMR spectrum substantially as shown in FIG. 2 .

5. The crystalline solid state form according to claim 1 characterised by a 13 C SSNMR spectrum comprising at least ten peaks, expressed as chemical shifts in ppm, selected from a group consisting of peaks at about 169.6, 167.5, 165.6, 160.1, 159.4, 157.1, 155.9, 154.3, 152.4, 146.9, 145.8, 140.0, 137.9, 135.9, 133.4, 132.0, 130.6, 129.9, 128.3, 127.1, 125.6, 123.5, 120.6, 119.1, 114.1, 113.7, 58.0, 53.6, 53.1, 40.7, 37.0, 34.9, 15.8, 14.7, and 12.0 (±0.2 ppm).

6. A pharmaceutical composition comprising the benzene sulphonic acid salt of 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide according to claim 1 and a pharmaceutically acceptable excipient.

7. The pharmaceutical composition according to claim 6 which is adapted for oral administration.

8. The pharmaceutical composition according to claim 7 in the form of a tablet comprising a pharmaceutically acceptable excipient that inhibits disproportionation.

9. The pharmaceutical composition according to claim 8 in which the pharmaceutically acceptable excipient that inhibits disproportionation is crospovidone.

10. A process for preparing a benzene sulphonic acid salt of 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide according to claim 1 comprising contacting 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide or a solvate thereof with benzene sulphonic acid.

11. The process according to claim 10 which comprises contacting an acetonitrile solvate of 2-[(4S)-6-(4-chlorophenyl)-1-methyl-8-(methyloxy)-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide with benzene sulphonic acid.

Assignees

• Glaxosmithkline Ip No 2 Ltd
• Glaxosmithkline Ip No 2 Ltd

Inventors

• Campbell Gossett Augustus
• Gladwin Asa Elisabeth

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P37/02

  Immunomodulators · CPC title