Amide compounds as ion channel ligands and uses thereof

Abstract

Compounds are disclosed that have a formula represented by the following: The compounds may be prepared as pharmaceutical compositions, and may be used for the prevention and treatment of a variety of conditions in mammals including humans, including by way of non-limiting example, pain, inflammation, traumatic injury, and others.

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         44 . A method for treating or managing a disease or condition which comprises administering to a patient in need of such treatment or management a therapeutically effective amount of a compound of the formula I′: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, or stereoisomers, or tautomers thereof, wherein:
 each of W, X, Y and Z is independently CR 4 ; 
 R 1′  is aryl, heteroaryl, aralkyl, heteroaralkyl, amino or substituted amino; 
 each R 4  is independently hydrogen, substituted or unsubstituted alkyl, hydroxyalkyl, haloalkyl, amino, alkylamino, dialkylamino, arylamino, alkylarylamino, alkoxy, aryloxy, heteroaryloxy, aminoalkoxy, alkoxy, cycloalkylalkoxy, alkoxycarbonyl, arylalkyloxy, aryl, heteroaryl, arylalkyl, sulfo, sulfonyl, sulfanyl, aminosulfonyl, arylsulfonyl, carboxy, carbamoyl, cyano, cycloheteroalkyl, halo, heteroalkyl, hydroxyl, or thiol; and 
 the subscript n and the subscript m are independently 0, 1, 2, 3, or 4. 
 
     
     
         45 . The method of  claim 44  wherein the disease or condition is a pain condition. 
     
     
         46 . The method of  claim 44  wherein the disease or condition is an autoimmune disease. 
     
     
         47 . The method of  claim 44  wherein the disease or condition is an inflammatory disease or condition. 
     
     
         48 . The method of  claim 44  wherein the disease or condition is a neurological or neurodegenerative disease or condition. 
     
     
         49 . A method for treating, ameliorating or managing a disease or condition, which comprises administering to a patient in need of such prevention, treatment or management a therapeutically acceptable amount of a compound of formula I′ 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, or stereoisomers, or tautomers thereof, wherein:
 each of W, X, Y and Z is independently CR 4 ; 
 R 1′  is aryl, heteroaryl, aralkyl, heteroaralkyl, amino or substituted amino; 
 each R 4  is independently hydrogen, substituted or unsubstituted alkyl, hydroxyalkyl, haloalkyl, amino, alkylamino, dialkylamino, arylamino, alkylarylamino, alkoxy, aryloxy, heteroaryloxy, aminoalkoxy, alkoxy, cycloalkylalkoxy, alkoxycarbonyl, arylalkyloxy, aryl, heteroaryl, arylalkyl, sulfo, sulfonyl, sulfanyl, aminosulfonyl, arylsulfonyl, carboxy, carbamoyl, cyano, cycloheteroalkyl, halo, heteroalkyl, hydroxyl, or thiol; and 
 the subscript n and the subscript m are independently 0, 1, 2, 3, or 4; and
 wherein the disease or condition is: pain including acute, inflammatory and neuropathic pain; chronic pain; dental pain; headache including migraine, cluster headache and tension headache; Parkinson's disease; Alzheimer's disease; multiple sclerosis; diseases and disorders mediated by or result in neuroinflammation, traumatic brain injury, stroke, or encephalitis; centrally-mediated neuropsychiatric diseases and disorders including depression, mania, bipolar disease, anxiety, schizophrenia, eating disorders, sleep disorders and cognition disorders; epilepsy and seizure disorders; prostate, bladder and bowel dysfunction, urinary incontinence, urinary hesitancy, rectal hypersensitivity, fecal incontinence, benign prostatic hypertrophy and inflammatory bowel disease; respiratory and airway disease and disorders including allergic rhinitis, asthma and reactive airway disease and chronic obstructive pulmonary disease; diseases and disorders mediated by or result in inflammation including arthritis, rheumatoid arthritis and osteoarthritis; myocardial infarction; autoimmune diseases and disorders; uveitis and atherosclerosis; itch/pruritus, psoriasis; alopecia (hair loss); obesity; lipid disorders; cancer; high blood pressure; spinal cord injury; or a renal disorder. 
 
 
     
     
         50 . The method of  claim 49  wherein the disease or condition is Parkinson's disease. 
     
     
         51 . The method of  claim 49  wherein the disease or condition is migraine. 
     
     
         52 . The method of  claim 49  wherein the disease or condition is overactive bladder. 
     
     
         53 . The method of  claim 49  wherein the disease or condition is osteoarthritis. 
     
     
         54 . The method of  claim 49  wherein the disease or condition is pain. 
     
     
         55 . The method of  claim 49  wherein the disease or condition is inflammatory pain 
     
     
         56 . The method of  claim 49  wherein the disease or condition is neuropathic pain. 
     
     
         57 . The method of  claim 49  wherein the disease or condition is dental pain