Tianeptine oxalate salts and polymorphs

• US 10,449,203 B2
• Filed: 12/28/2017
• Issued: 10/22/2019
• Est. Priority Date: 12/28/2016
• Status: Active Grant

• Current Assignee: Tonix pharma holdings limited (Tonix Pharmaceuticals Holding Corp.)
• Original Assignee: Tonix pharma holdings limited (Tonix Pharmaceuticals Holding Corp.)
• Inventors: Giaffreda, Stefano Luca, Modena, Enrico, Fabbroni, Serena, Chiarucci, Michel, Edgar, Mark T.
• Primary Examiner(s): Kosack, Joseph R
• Application Number:
  US15/856,818
• Publication Number:
  US 20180338984A1
• Time in Patent Office: 663 Days
• CPC Class Codes: A61K 31/554 having at least one nitrogen and one sulfur as ring hetero atoms, e.g. clothiapine, diltiazem
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 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 Class Codes: C07D 281/02 Seven-membered rings

Abstract

Disclosed herein is an oxalate salt/co-crystal (tianeptine oxalate) of (RS)-7-(3-chloro-6-methyl-6,11-dihydrodibenzo[c,f] [1,2]thiazepin-11-ylamino)heptanoic acid S,S-dioxide (tianeptine) as shown in Formula I:

Claims

1. An anhydrous crystalline hemi-oxalate salt of (RS)-7-(3-chloro-6-methyl-6,11-dihydrodibenzo[c,f] [1,2]thiazepin-11-ylamino)heptanoic acid S,S-dioxide (tianeptine), wherein the salt exhibits an X-ray diffraction pattern (XRPD) comprising at least one peak selected from the group consisting of 8.2, 8.6, 9.1, and 9.5 degrees 2θ

±

0.3 degrees 2θ

.

2. The compound of claim 1, wherein the tianeptine hemi-oxalate salt exhibits an XRPD pattern comprising at least one additional peak selected from the group consisting of 4.5, 11.5, 14.2, 15.2, 15.8, 16.4, 19.2, 22.1, 23.9, 26.9, and 27.4 degrees 2θ

±

0.3 degrees 2θ

.

3. An anhydrous crystalline tianeptine mono-oxalate salt of (RS)-7-(3-chloro-6-methyl-6,11-dihydrodibenzo[c,f] [1,2]thiazepin-11-ylamino)heptanoic acid S,S-dioxide (tianeptine), wherein the salt exhibits an X-ray diffraction pattern (XRPD) comprising at least one peak selected from the group consisting of 10.1 and 10.5 degrees 2θ

±

0.3 degrees 2θ

.

4. The compound of claim 3, wherein the crystalline tianeptine mono-oxalate salt exhibits an XRPD pattern comprising at least one additional peak selected from the group consisting of 7.5, 8.3, 11.9, 14.7, 16.2, 16.3, 17.9, 18.7, 21.0, 21.7, and 22.1 degrees 2θ

±

0.3 degrees 2θ

.

5. A mixture of an anhydrous hemi-oxalate salt and an anhydrous crystalline mono-oxalate salt of (RS)-7-(3-chloro-6-methyl-6,11-dihydrodibenzo[c,f] [1,2]thiazepin-11-ylamino)heptanoic acid S,S-dioxide (tianeptine), wherein the mixture exhibits an XRPD pattern comprising at least one peak selected from the group consisting of 10.1 and 10.5 degrees 2θ

±

0.3 degrees 2θ

.

6. The mixture of claim 5, wherein the mixture exhibits an XRPD pattern further comprising at least one additional peak selected from the group consisting of 7.5, 8.3, 11.9, 14.7, 16.2, 16.3, 17.9, 18.7, 21.0, 21.7, and 22.1 degrees 2θ

±

0.3 degrees 2θ

.