Metabolites of the Janus kinase inhibitor (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile

• US 7,834,022 B2
• Filed: 06/12/2008
• Issued: 11/16/2010
• Est. Priority Date: 06/13/2007
• Status: Active Grant

• Current Assignee: Incyte Holdings Corporation And Incyte Corporation
• Original Assignee: Incyte Corporation
• Inventors: Arvantis, Argyrios G., Shi, Jack Guoen, Shepard, Stacey, Rodgers, James D.
• Primary Examiner(s): Wilson; James O
• Assistant Examiner(s): Moore; Susanna
• Application Number:
  US12/137,883
• Publication Number:
  US 20080312258A1
• Time in Patent Office: 887 Days
• Field of Search: 544/280, 514/265.1
• US Class Current: 514/265.1
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C12N 9/99 Enzyme inactivation by chemical treatment

Abstract

The present invention provides active metabolites of 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile that modulate the activity of Janus kinases and are useful in the treatment of diseases related to activity of Janus kinases including, for example, immune-related diseases, skin disorders, myeloid proliferative disorders, cancer, and other diseases.

Claims

1. A compound selected from:

3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-hydroxycyclopentyl) propanenitrile;

3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(2-hydroxycyclopentyl) propanenitrile; and

3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-I-yl)-3-(3-oxocyclopentyl) propanenitrile,

or a pharmaceutically acceptable salt thereof;

which is substantially isolated.

2. A composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

3. The composition of claim 2 which is suitable for oral administration.

4. A method of treating a disease in a patient, wherein said disease is associated with Janus kinase activity, comprising administering to said patient a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof, wherein said disease is allograft rejection or graft versus host disease.

5. A composition according to claim 2, containing at least about 50% by weight of said compound or said salt.

6. A composition according to claim 2, containing at least about 90% by weight of said compound or said salt.

7. A composition according to claim 2, containing at least about 95% by weight of said compound or said salt.

8. A composition according to claim 2, containing at least about 99% by weight of said compound or said salt.

9. A compound according to claim 1, which is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-hydroxycyclopentyl)propanenitrile, or a pharmaceutically acceptable salt thereof.

10. A compound according to claim 1, which is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(2-hydroxycyclopentyl)propanenitrile, or a pharmaceutically acceptable salt thereof.

11. A compound according to claim 1, which is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-oxocyclopentyl)propanenitrile, or a pharmaceutically acceptable salt thereof.