Substituted pyridine and pyrazine compounds as pde4 inhibitors

Abstract

The invention provides a chemical entity of Formula (I), and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies, detection and imaging techniques, and radioactive treatments; and therapies, including inhibiting PDE4, enhancing neuronal plasticity, treating neurological disorders, providing neuroprotection, treating a cognitive impairment associated with a CNS disorder, enhancing the efficiency of cognitive and motor training, providing neurorecovery and neurorehabilitation, enhancing the efficiency of non-human animal training protocols, and treating treating peripheral disorders, including inflammatory and renal disorders.

1 .- 20 . (canceled) 
     
     
         21 . A compound selected from the group consisting of:
 5-{[5-(3-Chlorophenyl)-6-methoxypyridin-3-yl]methyl}pyrimidine-2-carboxamide;   4-{[5-(3-chlorophenyl)-6-methoxypyridin-3-yl]methyl}pyridine-2-carboxamide;   5-{[5-(3-Chlorophenyl)-6-(difluoromethoxy)pyridin-3-yl]methyl}pyridine-3-carboxamide;   (1-{[6-(Difluoromethoxy)-5-(3-ethoxyphenyl)pyridin-3-yl]methyl}-1H-1,2,4-triazol-3-yl)methanol; and   pharmaceutically acceptable salts thereof.   
     
     
         22 . The compound of  claim 21 , which is 5-{[5-(3-Chlorophenyl)-6-methoxypyridin-3-yl]methyl}pyrimidine-2-carboxamide; or a pharmaceutically acceptable salt thereof. 
     
     
         23 . The compound of  claim 21 , which is 4-{[5-(3-chlorophenyl)-6-methoxypyridin-3-yl]methyl}pyridine-2-carboxamide; or a pharmaceutically acceptable salt thereof. 
     
     
         24 . The compound of  claim 21 , which is 5-{[5-(3-Chlorophenyl)-6-(difluoromethoxy)pyridin-3-yl]methyl}pyridine-3-carboxamide; or a pharmaceutically acceptable salt thereof. 
     
     
         25 . The compound of  claim 21 , which is (1-{[6-(Difluoromethoxy)-5-(3-ethoxyphenyl)pyridin-3-yl]methyl}-1H-1,2,4-triazol-3-yl)methanol; or a pharmaceutically acceptable salt thereof. 
     
     
         26 . A pharmaceutical composition comprising an effective amount of a compound, or pharmaceutically acceptable salt thereof, of  claim 21 ; and a pharmaceutically acceptable excipient. 
     
     
         27 . A method of treating a subject suffering from or diagnosed with a disease, disorder, or medical condition mediated by PDE4 enzymatic activity, comprising administering to a subject in need of such treatment an effective amount of a compound of  claim 21 ,
 wherein the disorder is selected from one or more of the group selected from Alzheimer's Disease, Age Associated Memory Impairment (AAMI), Age Associated Cognitive Decline, vascular dementia, delirium, Parkinson's disease, Huntington's disease, Pick's disease, mental retardation, cerebrovascular disease, an affective disorder, psychotic disorders, neurotic disorders, attention deficit disorder, subdural hematoma, normal-pressure hydrocephalus, brain tumor, stroke, cognitive impairment due to sleep deprivation, intellectual and developmental disabilities; multiple sclerosis; inflammatory bowel disease; rheumatoid arthritis; COPD, asthma, allergic rhinitis, pulmonary artery hypertension; renal diseases; allergic skin diseases and psoriasis.   
     
     
         28 . A method of treating a neurological disorder, comprising administering to a subject in need of such treatment an effective amount of a compound of  claim 21 .