Compositions and methods for inhibition of the jak pathway

Abstract

Disclosed are compounds of formula I, compositions containing them, and methods of use for the compounds and compositions in the treatment of conditions in which modulation of the JAK pathway or inhibition of JAK kinases, particularly JAK 2 and JAK3, are therapeutically useful. Also disclosed are methods of making the compounds.

We claim: 
     
         1 . A pharmaceutical composition, comprising:
 a means for inhibiting a Janus kinase (JAK); and   a pharmaceutically acceptable excipient.   
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutically acceptable excipient is a liquid carrier. 
     
     
         3 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutically acceptable excipient is a solid carrier. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is formulated for oral administration, parenteral administration, inhalation spray nasal administration, vaginal administration, rectal administration, sublingual administration, urethral administration, or topical administration. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein parenteral administration is selected from intramuscular, intraperitoneal, intravenous, ICV, intracisternal injection or infusion, subcutaneous injection, or implant administration. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is a gel, ointment, cream, aerosol, a semi-solid, a solid, a powder, a tablet, a suppository, a pill, a soft elastic capsule, a jelly, a hard gelatin capsule, a solution, a suspension, or a combination thereof. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutically acceptable excipient is selected from binding agents, fillers, lubricants, disintegrants, wetting agents, inert diluents, granulating agents, tonicity agents, or disintegrating agents. 
     
     
         8 . The pharmaceutical composition of  claim 1 , further comprising a sweetening agent, a flavoring agent, a coloring agent, a preserving agent, a suspending agent, an emulsifying agent, a non-aqueous vehicle, a preservative, a buffer salt, a surfactant, a stabilizing polymer, a propellant, or a combination thereof. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the pharmaceutical composition is formulated for treating or preventing a JAK-mediated disease. 
     
     
         10 . The pharmaceutical composition of  claim 9 , wherein the JAK-mediated disease is selected from allergies, asthma, transplant rejection, rheumatoid arthritis, amyotrophic lateral sclerosis, multiple sclerosis, psoriasis, Sjogren's syndrome, vascular inflammation, stroke, pulmonary diseases, solid, delayed Type IV hypersensitivity reactions, or hematologic malignancies. 
     
     
         11 . The pharmaceutical composition of  claim 1 , wherein the JAK is JAK2, JAK3, or both. 
     
     
         12 . The pharmaceutical composition of  claim 1 , wherein the means for inhibiting the JAK is a 2,4-pyrimidinediamine compound. 
     
     
         13 . A method, comprising contacting the JAK with an amount of the pharmaceutical composition of  claim 1  effective to inhibit an activity of the JAK. 
     
     
         14 . A method of treating a JAK-mediated disease, comprising administering the pharmaceutical composition of  claim 1  to a subject. 
     
     
         15 . The method of  claim 14 , wherein the JAK-mediated disease is a JAK2-mediated disease and/or a JAK3-mediated disease. 
     
     
         16 . The method of  claim 14 , wherein the JAK-mediated disease is selected from allergies, asthma, transplant rejection, rheumatoid arthritis, amyotrophic lateral sclerosis, multiple sclerosis, psoriasis, Sjogren's syndrome, vascular inflammation, stroke, pulmonary diseases, solid, delayed Type IV hypersensitivity reactions, or hematologic malignancies.