Salts, co-crystals, and polymorphs of an anxiolytic compound

Patent metadata

Field	Value
Publication number	US-9745296-B2
Application number	US-201414776643-A
Country	US
Kind code	B2
Filing date	Mar 14, 2014
Priority date	Mar 15, 2013
Publication date	Aug 29, 2017
Grant date	Aug 29, 2017

Abstract

The present invention provides amorphous arid crystalline forms of 1-ethyl-6-(indan-2-ylamino)-3-(morpholine-4-carbonyl)-1,8-naphthyridin-4-one (compound 1), and salts, co-crystals, and pharmaceutical compositions thereof. The invention also provides methods of treating and/or preventing a disease, such as a central nervous system disease (e.g., an anxiety disorder), using the amorphous and crystalline forms, and salts, co-crystals, and pharmaceutical compositions thereof.

First claim

What is claimed is:

1. A hemi-succinate salt of the crystalline Form SUC-P5 of compound 1:

2. The crystalline Form SUC-P5 of claim 1 , wherein the crystalline Form SUC-P5 is substantially free of impurities.

3. The crystalline Form SUC-P5 of claim 1 , wherein the crystalline Form SUC-P5 is substantially free of amorphous compound 1.

4. The crystalline Form SUC-P5 of claim 1 , wherein the crystalline Form SUC-P5 has two or more peaks in its x-ray powder diffraction (XRPD) pattern selected from those in the following table:

Angle

2-Theta °

7.4

15.6

16.5

18.5

22.2.

5. The crystalline Form SUC-P5 of claim 1 , wherein the crystalline Form SUC-P5 has four or more peaks in its XRPD pattern selected from those in the following table:

Angle

2-Theta °

7.4

8.3

10.5

11.7

13.2

15.6

16.5

18.5

22.2.

6. The crystalline Form SUC-P5 of claim 1 , wherein the crystalline Form SUC-P5 is characterized by a differential scanning calorimetry (DSC) thermogram with an endotherm having a peak temperature (T max ) of about 207° C.

7. The crystalline Form SUC-P5 of claim 1 , wherein the crystalline Form SUC-P5 is characterized by a DSC thermogram with a ΔH of about 6.7 J/g or about 92.6 J/g.

8. A pharmaceutical composition comprising the crystalline form SUC-P5 of claim 1 , and optionally a pharmaceutically acceptable excipient.

9. The pharmaceutical composition of claim 8 , wherein the crystalline form SUC-P5 is of a therapeutically effective amount.

10. A method of treating an anxiety disorder or depression in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition of claim 8 .

11. The method of claim 10 , wherein the depression is major depressive disorder (MDD), bipolar disorder (BD), atypical depression, melancholic depression, psychotic major depression, catatonic depression, postpartum depression, seasonal affective disorder, dysthymia, a depressive disorder not otherwise specified (DD-NOS), or a substance induced mood disorder.

12. The method of claim 10 , wherein the anxiety disorder is panic disorder, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), generalized anxiety disorder (GAD), substance-induced anxiety disorder, acute stress disorder (ASD), irritable bowel syndrome, or fibromyalgia.

13. The method of claim 10 , wherein the anxiety disorder is a phobia.

14. The method of claim 10 , wherein the phobia is social phobia, agoraphobia, or animal phobia.

15. The method of claim 10 , wherein the subject is a human.

Assignees

• Bionomics Ltd
• Ironwood Pharmaceuticals Inc

Inventors

• Flynn Bernard Luke
• Paul Dharam
• Harvey Andrew John
• Sethuraman Vasu V
• Forslund Raymond E
• Xue Song
• Livingston Rob
• Hashash Ahmad

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61P25/24

  Antidepressants · CPC title