Crystalline N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamic hydrochloride

• US 8,609,711 B2
• Filed: 01/28/2010
• Issued: 12/17/2013
• Est. Priority Date: 01/30/2009
• Status: Active Grant

• Current Assignee: Novartis Ag
• Original Assignee: GlaxoSmithKline LLC (GlaxoSmithKline PLC)
• Inventors: Chen, Pingyun Y., Gaulding, Jeffrey
• Primary Examiner(s): Jarrell, Noble
• Assistant Examiner(s): Rodriguez-Garcia, Valerie
• Application Number:
  US12/695,331
• Publication Number:
  US 20100197754A1
• Time in Patent Office: 1,419 Days
• Field of Search: 514/406, 548/365.7
• US Class Current: 514/406
• CPC Class Codes: A61K 31/4155 non condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• 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 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 409/04 directly linked by a ring-member-to-ring-member bond

Abstract

An improved AKT inhibiting compound, crystalline N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide hydrochloride.

Claims

1. The compound N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide hydrochloride in crystalline form, made by a process comprising the steps of:

a) adding N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide and methyl t-butyl ether to form a mixture;

b) adding HCl acid to the mixture and stir at above room temperature;

c) allowing the mixture to return to room temperature; and

d) isolate and dry the prepared compound.

2. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or diluent.

3. A process for preparing a pharmaceutical composition containing a pharmaceutically acceptable carrier and an effective amount of a compound of claim 1, which process comprises bringing the compound of claim 1 into association with a pharmaceutically acceptable carrier.

4. A method of inhibiting Akt activity in a mammal, which comprises administering to such mammal an inhibitory amount of a compound of claim 1.

5. The method of claim 4 wherein the mammal is a human.

6. Crystalline N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide hydrochloride having characteristic diffraction peaks at 14.4°

±

0.3° and

32.4°

±

0.3°

in an Powder X-Ray Diffractogram using Cu Kα

radiation.

7. Crystalline N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide hydrochloride having the characteristic diffraction peaks recited in claim 6 and having characteristic diffraction peaks at 25.1°

±

0.3° and

25.7°

±

0.3°

in the Powder X-Ray Diffractogram using Cu Kα

radiation.

8. Crystalline N-{(1S)-2-amino-1-[(3-fluorophenyl)methyl]ethyl}-5-chloro-4-(4-chloro-1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide hydrochloride having the characteristic diffraction peaks recited in claim 7 and having characteristic diffraction peaks at 21.5°

±

0.3° and

20.8°

±

0.3°

in the Powder X-Ray Diffractogram using Cu Kα

radiation.

9. A pharmaceutical composition comprising the compound of claim 6 and a pharmaceutically acceptable carrier or diluent.

10. A method of inhibiting Akt activity in a mammal, which comprises administering to such mammal an inhibitory amount of a compound of claim 6.

11. The method of claim 10 wherein the mammal is a human.