Imidazolecarboxamides and Their Use as FAAH Inhibitors

Abstract

or a pharmaceutically acceptable salt thereof. The compound may be used as an inhibitor of fatty acid amide hydrolase.

1 . A compound having a structure selected from the following: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 . A pharmaceutical composition comprising a compound according to  claim 1 , together with one or more pharmaceutically acceptable excipients. 
     
     
         3 . The pharmaceutical composition of  claim 2 , further comprising one or more additional active pharmaceutical ingredients. 
     
     
         4 - 5 . (canceled) 
     
     
         6 . A method of treatment or prevention of a condition whose development or symptoms are linked to a substrate of the FAAH enzyme, the method comprising the administration, to a subject in need of such treatment or prevention, of a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         7 . A method according to  claim 6 , wherein the condition is a disorder associated with the endocannabinoid system. 
     
     
         8 . A method according to  claim 7 , wherein the disorder is selected from the group consisting of appetite regulation, obesity, metabolic disorders, cachexia, anorexia, pain, inflammation, neurotoxicity, neurotrauma, stroke, multiple sclerosis, spinal cord injury, Parkinson's disease, levodopa-induced dyskinesia, Huntington's disease, Gilles de la Tourette's syndrome, tardive dyskinesia, dystonia, amyotrophic lateral sclerosis, Alzheimer's disease, epilepsy, schizophrenia, anxiety, depression, insomnia, nausea, emesis, alcohol disorders, drug addictions, hypertension, circulatory shock, myocardial reperfusion injury, atherosclerosis, asthma, ocular hypertension, glaucoma, retinopathy, cancer, inflammatory bowel disease, acute and chronic liver disease, arthritis, and osteoporosis. 
     
     
         9 . The compound of  claim 1 , wherein the pharmaceutically acceptable salt is selected from the group consisting of a hydrochloride salt, acetate salt, trifluoroacetate salt, methanesulfonate salt, 2-hydroxypropane-1,2,2-tricarboxylate salt, (2R,3R)-2,3-dihydroxysuccinate salt, phosphate salt, sulphate salt, benzoate salt, 2-hydroxy-benzoate salt, S-(+)-mandelate salt, S-(−)-malate salt, S-(−) pyroglutamate salt, pyruvate salt, p-toluenesulfonate salt, 1-R-(−)-camphorsulfonate salt, fumarate salt, maleate salt and oxalate salt. 
     
     
         10 . The pharmaceutical composition of  claim 2 , wherein the composition is formulated for oral administration. 
     
     
         11 . The pharmaceutical composition of  claim 2 , wherein the composition is in the form of a sterile injectable preparation. 
     
     
         12 . The pharmaceutical composition of  claim 3 , wherein the one or more active pharmaceutical ingredients are selected from the group consisting of anandamide, oleoyl ethanolamide, and palmitoyl ethanolamide. 
     
     
         13 . The method of  claim 8 , wherein the disorder is a drug addiction, and the drug is selected from the group consisting of opiates, nicotine, cocaine, alcohol, and psychostimulants. 
     
     
         14 . The method of  claim 8 , wherein the disorder is an acute or chronic liver disease, and the liver disease is hepatitis or liver cirrhosis. 
     
     
         15 . The method of  claim 6 , wherein the compound is administered simultaneously with, or staggered with respect to, one or more additional active pharmaceutical ingredients. 
     
     
         16 . The method of  claim 15 , wherein the one or more additional active pharmaceutical ingredients are selected from the group consisting of anandamide, oleoyl ethanolamide and palmitoyl ethanolamide.