Novel crystalline compound

• US 20030130292A1
• Filed: 12/04/2002
• Published: 07/10/2003
• Est. Priority Date: 12/06/2001
• Status: Active Grant

• Current Assignee: Pfizer Inc., Pfizer Products Incorporated (Pfizer Inc.)
• Original Assignee: Pfizer Inc.
• Inventors: Li, Zheng J., Flanagan, Mark E.
• Granted Patent: US 6,965,027 B2
• Time in Patent Office: Days
• US Class Current: 514/265.1
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/06 Antipsoriatics
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 37/08 Antiallergic agents antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 487/04 Ortho-condensed systems

Abstract

This invention relates to novel amorphous and crystallline forms of 3-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile mono citrate salt, useful as inhibitors of protein kinases, and to their methods of preparation.

Claims

1. A crystalline form of 3-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile mono citrate salt.

2. A crystalline form of 3-{4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile mono citrate salt according to claim 1, comprising an x-ray powder diffraction pattern having characteristic peaks expressed in degrees two-theta at approximately 5.7, 16.1, 20.2 and 20.5.

3. A crystalline form according to claim 2, comprising a powder diffraction pattern having characteristic peaks expressed in degree of 2-theta at approximately:

4. A crystalline form of 3-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile mono citrate salt according to claim 1, having an onset melting temperature of between about 199°

C. to about 206°

C.

6. A pharmaceutical composition for (a) treating or preventing a disorder or condition selected from organ transplant rejection, xeno transplation, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn'"'"'s disease, Alzheimer'"'"'s disease, leukemia and other autoimmune diseases or (b) the inhibition of protein kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising an amount of a compound of claim 1, effective in such disorders or conditions and a pharmaceutically acceptable carrier.

7. A pharmaceutical composition for (a) treating or preventing a disorder or condition selected from organ transplant rejection, xeno transplation, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn'"'"'s disease, Alzheimer'"'"'s disease, leukemia and other autoimmune diseases or (b) the inhibition of protein kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising an amount of a compound of claim 1, alone or in combination with one or more additional agents which modulate a mammalian immune system or with antiinflammatory agents, effective in such disorders or conditions and a pharmaceutically acceptable carrier.

8. A method for the inhibition of protein kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising administering to said mammal an effective amount of a compound of claim 1.

9. A method for treating or preventing a disorder or condition selected from organ transplant rejection, xeno transplation, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn'"'"'s disease, Alzheimer'"'"'s disease, leukemia and other autoimmune diseases in a mammal, including a human, comprising administering to said mammal an amount of a compound of claim 1, effective in treating such a condition.

10. A method for the inhibition of protein kinases or Janus Kinase 3 (JAK3) in a mammal, including a human, comprising administering to said mammal an effective amount of a compound of claim 1, alone or in combination with one or more additional agents which modulate a mammalian immune system or with antiinflammatory agents.

11. A method for treating or preventing a disorder or condition selected from organ transplant rejection, xeno transplation, lupus, multiple sclerosis, rheumatoid arthritis, psoriasis, Type I diabetes and complications from diabetes, cancer, asthma, atopic dermatitis, autoimmune thyroid disorders, ulcerative colitis, Crohn'"'"'s disease, Alzheimer'"'"'s disease, leukemia and other autoimmune diseases in a mammal, including a human, comprising administering to said mammal an amount of a compound of claim 1, alone or in combination with one or more additional agents which modulate a mammalian immune system or with antiinflammatory agents, effective in treating such a condition.

5. An amorphous form of 3-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile mono citrate salt

12. A process for preparing 3-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile mono citrate salt comprising reacting 3-{(3R,4R)-4-methyl-3-[methyl-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-amino]-piperidin-1-yl}-3-oxo-propionitrile with citric acid.