4-substituted azaadamantane derivatives and methods of use thereof

Abstract

The invention relates to compounds that are 4-substituted azaadamantane derivatives, compositions comprising such compounds, and methods of using such compounds and compositions.

1 .- 8 . (canceled) 
     
     
         9 . A method for treating a disorder selected from the group consisting of mild cognitive impairment, age-associated memory impairment (AAMI), senile dementia, AIDS dementia, Pick's Disease, dementia associated with Lewy bodies, dementia associated with Down's syndrome, amyotrophic lateral sclerosis, Huntington's disease, smoking cessation, schizoaffective disorder, bipolar and manic disorders, diminished CNS function associated with traumatic brain injury, acute pain, post-surgical pain, chronic pain, and inflammatory pain, said method comprising the step of administering to a subject in need thereof the compound of the formula (I), or a pharmaceutically acceptable salt, amide or prodrug thereof, wherein the compound of formula I comprises: 
       
         
           
           
               
               
           
         
       
       wherein
 Y 1  is a bond, —N(R X )—C(O)—, —O—, —N(R X )—C(O)—N(R Y )—, —O—C(O)—, or —N(R Z )—; 
 A is aryl, heteroaryl, heterocycle, cycloalkyl, cycloalkenyl, arylalkyl, heteroarylalkyl, heterocyclealkyl, cycloalkylalkyl, or cycloalkenylalkyl wherein the aryl, heteroaryl, heterocycle, cycloalkyl, cycloalkenyl, the aryl moiety of arylalkyl, the heteroaryl moiety of the heteroarylalkyl, the heterocycle moiety of the heterocyclealkyl, the cycloalkyl moiety of the cycloalkylalkyl, and the cycloalkenyl moiety of the cycloalkenylalkyl are each independently unsubstituted or substituted; and 
 R X , R Y , and R Z , at each occurrence, are each independently hydrogen, alkyl, or haloalkyl; 
 or a pharmaceutically acceptable salt, amide or prodrug thereof. 
 
     
     
         10 . A method for treating a disorder selected from the group consisting of attention deficit disorder, attention deficit hyperactivity disorder (ADHD), Alzheimer's disease (AD), Parkinson's disease, Tourette's syndrome, schizophrenia, and cognitive deficits associated with schizophrenia (CDS), said method comprising the step of administering to a subject in need thereof the compound of  claim 9 , or a pharmaceutically acceptable salt, amide or prodrug thereof. 
     
     
         11 . A method for treating disorder selected from the group consisting of schizophrenia and cognitive deficits associated with schizophrenia (CDS), or combination thereof, comprising the step of administering to a subject in need thereof the compound of  claim 9 , or a pharmaceutically acceptable salt, amide or prodrug thereof, and one or more atypical antipsychotics. 
     
     
         12 - 13 . (canceled) 
     
     
         14 . The method of  claim 9 , wherein the compound is selected from the group consisting of
 1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-2-naphthyloxime;   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-(pentafluorobenzyl)oxime;   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-(4-chlorophenyl)oxime;   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-(6-chloropyridin-3-yl)oxime;   N-1-azatricyclo[3.3.1.1 3,7 ]dec-4-ylidene-1H-indole-3-carbohydrazide; and   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-benzyloxime;   
       or a pharmaceutically acceptable salt, amide or prodrug thereof. 
     
     
         15 . The method of  claim 10 , wherein the compound is selected from the group consisting of
 1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-2-naphthyloxime;   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-(pentafluorobenzyl)oxime;   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-(4-chlorophenyl)oxime;   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-(6-chloropyridin-3-yl)oxime;   N-1-azatricyclo[3.3.1.1 3,7 ]dec-4-ylidene-1H-indole-3-carbohydrazide; and   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-benzyloxime;   
       or a pharmaceutically acceptable salt, amide or prodrug thereof. 
     
     
         16 . The method of  claim 11 , wherein the compound is selected from the group consisting of
 1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-2-naphthyloxime;   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-(pentafluorobenzyl)oxime;   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-(4-chlorophenyl)oxime;   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-(6-chloropyridin-3-yl)oxime;   N-1-azatricyclo[3.3.1.1 3,7 ]dec-4-ylidene-1H-indole-3-carbohydrazide; and   1-azatricyclo[3.3.1.1 3,7 ]decan-4-one O-benzyloxime;   
       or a pharmaceutically acceptable salt, amide or prodrug thereof.