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

• US 8,889,697 B2
• Filed: 10/07/2010
• Issued: 11/18/2014
• Est. Priority Date: 06/13/2007
• Status: Active Grant

• Current Assignee: Incyte Holdings Corporation And Incyte Corporation
• Original Assignee: Incyte Corporation
• Inventors: Rodgers, James D., Arvanitis, Argyrios G., Shi, Jack Guoen, Shepard, Stacey
• Primary Examiner(s): Moore, Susanna
• Application Number:
  US12/900,180
• Publication Number:
  US 20110082159A1
• Time in Patent Office: 1,503 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 method of treating cancer in a patient, comprising administering to said patient a therapeutically effective amount of a compound selected from the group consisting of:

3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)-1H-pyrazol-1-y1)-3-(3-hydroxycyclopentyl)propanenitrile;

3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)-1H-pyrazol-1-y1)-3-(2-hydroxycyclopentyl)propanenitrile; and

3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)-1H-pyrazol-1-y1)-3-oxocyclopentyl)propanenitrile,

or a pharmaceutically acceptable salt thereof;

wherein said cancer is pancreatic cnacer, chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), or chronic myelomonocytic leukemia (CMML); and

wherein said treating refers to ameliorating or inhibiting the disease in a patient.

3. The method of claim 1, wherein said cancer is chronic myelogenous leukemia (CML) or acute myelogenous leukemia (AML).

4. The method of claim 1, wherein said cancer is acute lymphoblastic leukemia (ALL).

5. The method of claim 1, wherein said cancer is chronic myelomonocytic leukemia (CMML).

6. The method of claim 1, wherein said cancer is pancreatic cancer.

2. A method of treating myeloid metaplasia with myelofibrosis (MMM), polycythemia vera (PV), or essential thrombocythemia (ET) in a patient, comprising administering to said patient a therapeutically effective amount of a compound selected from the group consisting of:

3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)- 1H-pyrazol-1-y1)-3-(3-hydroxycyclopentyl)propanenitrile;

3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)-1H-pyrazol-1-y1)-3-(2-hydroxycyclopentyl)propanenitrile; and

3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-y1)-1H-pyrazol-1-y1)-3-(3oxocyclopentyppropanenitrile,

or a pharmaceutically acceptable salt thereof, wherein said treating refers to ameliorating or inhibiting the disease in a patient.