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

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.

1 - 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.