Salts and solid form of a BTK inhibitor

• US 10,456,403 B2
• Filed: 08/29/2018
• Issued: 10/29/2019
• Est. Priority Date: 02/21/2014
• Status: Active Grant

• Current Assignee: Principia Biopharma Inc. (Sanofi )
• Original Assignee: Principia Biopharma Inc. (Sanofi )
• Inventors: Masjedizadeh, Mohammad Reza, Gourlay, Steven
• Primary Examiner(s): Murray, Jeffrey H
• Application Number:
  US16/116,425
• Publication Number:
  US 20190076435A1
• Time in Patent Office: 426 Days
• Field of Search: 5142621, 544262
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/5395 having two or more nitrogen atoms in the same ring, e.g. oxadiazines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/38 Cellulose; Derivatives thereof
• CPC Class Codes: A61K 9/0014 Skin, i.e. galenical aspects of topical compositions non-active ingredients are additionally classified in A61K47/00; A61K9/0009, A61K9/0021, A61K9/7015, A61K9/7023 take precedence; cosmetic preparations A61K8/00, A61Q; preparations for wound dressings or bandages A61L26/00
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/0043 Nose
• CPC Class Codes: A61K 9/0048 Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/0078 for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
• CPC Class Codes: A61K 9/2018 Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 487/04 : Ortho-condensed systems

Abstract

Disclosed herein are processes for preparing 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile free base (compound (I)), salts of compound (I) and solid state form of said salts. Also disclosed herein are pharmaceutical compositions comprising such salts and solid state form thereof and methods of treating cancer, autoimmune, and inflammatory diseases using compound (I) or a pharmaceutically acceptable salt thereof.

Claims

1. A sulfonic acid or carboxylic acid salt of at least one compound selected from (E) isomer, (Z) isomer, and a mixture of (E) and (Z) isomer of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]-pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile.

2. The sulfonic acid or carboxylic acid salt of the at least one compound of claim 1, wherein the salt is a sulfonic acid salt.

3. The sulfonic acid salt of the at least one compound of claim 2, wherein the sulfonic salt is mono- or di-methanesulfonic acid salt.

10. The sulfonic acid or carboxylic acid salt of the at least one compound of claim 1, wherein the salt of the at least one compound is a substantially pure E or Z isomer.

12. The sulfonic acid or carboxylic acid salt of the at least one compound of claim 10, wherein at least about 80% w/w of the salt of the at least one compound is the E isomer.

13. The sulfonic acid or carboxylic acid salt of the at least one compound of claim 10, wherein at least about 90% w/w of the salt of the at least one compound is the E isomer.

16. A pharmaceutical composition comprising:

the sulfonic acid or carboxylic acid salt of the at least one compound of claim 1; and

a pharmaceutically acceptable excipient.

4. An amorphous form of a pharmaceutically acceptable salt of at least one compound selected from (E) isomer, (Z) isomer, and a mixture of (E) and (Z) isomer of 2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]-pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile.

5. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4, wherein the pharmaceutically acceptable salt is a sulfonic acid or a carboxylic acid salt.

6. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4, wherein the pharmaceutically acceptable salt is a sulfonic acid salt.

7. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 6, wherein the sulfonic acid salt is mono- or di-methanesulfonic acid salt.

8. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4, wherein the amorphous form is substantially free of any crystalline form(s) of the pharmaceutically acceptable salt of the at least one compound.

9. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4, wherein at least about 90% w/w of the pharmaceutically acceptable salt of the at least one compound is in amorphous form.

11. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4, wherein the salt of the at least one compound is a substantially pure E or Z isomer.

14. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 11, wherein at least about 80% w/w of the pharmaceutically acceptable salt of the at least one compound is the E isomer.

15. The amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 11, wherein at least about 90% w/w of the pharmaceutically acceptable salt of the at least one compound is the E isomer.

17. A pharmaceutical composition comprising:

the amorphous form of the pharmaceutically acceptable salt of the at least one compound of claim 4; and

a pharmaceutically acceptable excipient.