METABOLITES OF THE JANUS KINASE INHIBITOR (R)-3-(4-(7H-PYRROLO[2,3-d]PYRIMIDIN-4-YL)-1H-PYRAZOL-1-YL)-3-CYCLOPENTYLPROPANENITRILE

• US 20150164900A1
• Filed: 10/20/2014
• Published: 06/18/2015
• Est. Priority Date: 06/13/2007
• Status: Abandoned Application

• Current Assignee: Incyte Holdings Corporation And Incyte Corporation
• Original Assignee: Incyte Corporation
• Inventors: Rodgers, James D., Arvanitis, Argyrios G., Shi, Jack Guoen, Shepard, Stacey
• Application Number:
  US14/518,419
• Publication Number:
  US 20150164900A1
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 metablites 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

1-53. -53. (canceled)

54. A method of treating a myeloproliferative disorder in a patient in need thereof, comprising administering to the patient a metabolite 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-1-yl)-3-(3-oxycyclopentyl)propanenitrile,

wherein the metabolite is generated as a result of administration of (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile or a pharmaceutically acceptable salt thereof to the patient.

55. The method of claim 54, wherein the myeloproliferative disorder is polycythemia vera (PV).

56. The method of claim 54, wherein the myeloproliferative disorder is essential thrombocythemia (ET).

57. The method of claim 54, wherein the myeloproliferative disorder is myeloid metaplasia with myelofibrosis (MMM).

58. The method of claim 54, wherein the metabolite is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-hydroxycyclopentyl)propanenitrile.

59. The method of claim 54, wherein the metabolite is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(2-hydroxycyclopentyl)propanenitrile.

60. The method of claim 54, wherein the metabolite is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-oxycyclopentyl)propanenitrile.