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 - 6 . (canceled) 
     
     
         7 . A method of treating an autoimmune skin disease in a patient, comprising administering to said patient a therapeutically effective amount of 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-1-yl)-3-(3-oxocyclopentyl)-propanenitrile,   or a pharmaceutically acceptable salt thereof,   and a pharmaceutically acceptable carrier.   
     
     
         8 - 10 . (canceled) 
     
     
         11 . The method of  claim 7 , wherein said autoimmune skin disease is bullous skin disorder. 
     
     
         12 . The method of  claim 11 , wherein said bullous skin disorder is pemphigus vulgaris (PV) or bullous pemphigoid (BP). 
     
     
         13 . (canceled) 
     
     
         14 . The method of  claim 7 , wherein said autoimmune skin disease is atopic dermatitis, psoriasis, skin sensitization, skin irritation, skin rash, contact dermatitis or allergic contact sensitization. 
     
     
         15 - 53 . (canceled) 
     
     
         54 . The method of  claim 11 , wherein the bullous skin disorder is pemphigus vulgaris (PV). 
     
     
         55 . The method of  claim 11 , wherein the bullous skin disorder is bullous pemphigoid (BP). 
     
     
         56 . The method of  claim 14 , wherein the autoimmune skin disease is atopic dermatitis. 
     
     
         57 . The method of  claim 14 , wherein the autoimmune skin disease is psoriasis. 
     
     
         58 . The method of  claim 7 , wherein about 5 to about 1000 mg of the compound, or pharmaceutically acceptable salt thereof, is administered to the patient. 
     
     
         59 . The method of  claim 7 , further comprising administering to the patient at least one additional therapeutic agent. 
     
     
         60 . The method of  claim 59 , wherein the therapeutic agent is administered to a patient simultaneously or sequentially. 
     
     
         61 . The method of  claim 59 , wherein said therapeutic agent is an immunosuppressant. 
     
     
         62 . The method of  claim 59 , wherein said therapeutic agent is a steroid. 
     
     
         63 . The method of  claim 59 , wherein said therapeutic agent is a corticosteroid. 
     
     
         64 . The method of  claim 63 , wherein said corticosteroid is dexamethasone or prednisone. 
     
     
         65 . The method of  claim 7 , wherein the compound is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-hydroxycyclopentyl)propanenitrile. 
     
     
         66 . The method of  claim 7 , wherein the compound is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(2-hydroxycyclopentyl)propanenitrile. 
     
     
         67 . The method of  claim 7 , wherein the compound is 3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-(3-oxycyclopentyl)propanenitrile. 
     
     
         68 . The method of  claim 7 , wherein the pharmaceutical composition is suitable for oral administration. 
     
     
         69 . The method of  claim 7 , wherein the pharmaceutical composition is in tablet form.