Heteroaryl Substituted Pyrrolo[2,3-B] Pyridines And Pyrrolo[2,3-B] Pyrimidines As Janus Kinase Inhibitors

Abstract

The present invention provides heteroaryl substituted pyrrolo[2,3-b]pyridines and heteroaryl substituted pyrrolo[2,3-b]pyrimidines 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 - 88 . (canceled) 
     
     
         89 . A method of treating a skin disorder in a patient, comprising administering to the skin of said patient a compound, which is 3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof; wherein said administering is topical administration. 
     
     
         90 . The method of  claim 89 , wherein the compound is (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof. 
     
     
         91 . The method of  claim 90 , wherein said topical administration is transdermal administration. 
     
     
         92 . The method of  claim 90 , wherein said topical administration is transdermal administration epidermal administration. 
     
     
         93 . The method of  claim 90 , wherein said compound or salt is administered in the form of a pharmaceutical composition comprising said compound or salt and a pharmaceutically acceptable carrier. 
     
     
         94 . The method of  claim 93 , wherein said pharmaceutical composition is a cream. 
     
     
         95 . The method of  claim 93 , wherein said pharmaceutical composition is an ointment. 
     
     
         96 . The method of  claim 93 , wherein said pharmaceutical composition is a lotion. 
     
     
         97 . The method of  claim 93 , wherein said pharmaceutical composition is a gel. 
     
     
         98 . The method of  claim 90 , wherein a therapeutically effective amount of said compound or salt is administered to the skin of said patient. 
     
     
         99 . The method of  claim 98 , wherein the skin disorder is psoriasis. 
     
     
         100 . The method of  claim 98 , wherein the skin disorder is psoriasis vulgaris. 
     
     
         101 . The method of  claim 98 , wherein skin disorder is atopic dermatitis, skin rash, skin irritation, or skin sensitization. 
     
     
         102 . The method of  claim 90 , wherein the individual is need of inhibition of JAK1 and/or JAK2. 
     
     
         103 . A pharmaceutical composition, comprising a compound, which is (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, wherein said pharmaceutical composition is suitable for topical administration. 
     
     
         104 . The pharmaceutical composition of  claim 103 , wherein the compound is a pharmaceutical salt of (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile. 
     
     
         105 . The pharmaceutical composition of  claim 103 , wherein said composition is a cream. 
     
     
         106 . The pharmaceutical composition of  claim 103 , wherein said composition is an ointment. 
     
     
         107 . The pharmaceutical composition of  claim 103 , wherein said composition is a lotion. 
     
     
         108 . The pharmaceutical composition of  claim 103 , wherein said composition is a gel. 
     
     
         109 . The pharmaceutical composition of  claim 103 , wherein said composition is suitable for epidermal administration. 
     
     
         110 . A method of treating a JAK-associated disease in a patient, comprising administering to the skin of said patient a compound, which is 3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof; wherein said administering is topical administration. 
     
     
         111 . The method of  claim 110 , wherein the compound is (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof. 
     
     
         112 . The method of  claim 111 , wherein said topical administration is transdermal. 
     
     
         113 . The method of  claim 111 , wherein said topical administration is epidermal. 
     
     
         114 . The method of  claim 111 , wherein said compound or salt is administered in the form of pharmaceutical composition comprising said compound or salt and a pharmaceutically acceptable carrier. 
     
     
         115 . The method of  claim 114 , wherein said pharmaceutical composition is a cream. 
     
     
         116 . The method of  claim 114 , wherein said pharmaceutical composition is an ointment. 
     
     
         117 . The method of  claim 114 , wherein said pharmaceutical composition is a lotion. 
     
     
         118 . The method of  claim 114 , wherein said pharmaceutical composition is a gel. 
     
     
         119 . The method of  claim 111 , wherein the JAK-associated skin disease in a patient is associated with inhibiting JAK1 and/or JAK2 in a patient in need thereof. 
     
     
         120 . A method of inhibiting JAK1 and/or JAK2 associated with a skin disease in a patient in need thereof, comprising administering to the skin of said patient a compound, which is (3R)-3-cyclopentyl-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanenitrile, or a pharmaceutically acceptable salt thereof; wherein said administering is topical administration.