SirT INHIBITORS THAT BIND TO NAD

Abstract

Compound of formula (I) and methods of treating disorders by administering a compound of formula (I) are described herein. Examples of disorders include neoplastic disorders, fat-cell related disorders, neurodegenerative disorders, and metabolic disorders.

What is claimed is: 
     
         1 . A method of treating a neurodegenerative disease or disorder in which the neurodegenerative disorder can be mediated at least in part by polyglutamine aggregation, the method comprising administering a compound of formula (XI): 
       
         
           
           
               
               
           
         
         wherein 
         R 6  is halo, hydroxy, C 1 -C 10  alkyl, C 1 -C 6  haloalkyl, C 1 -C 10  alkoxy, C 1 -C 6  haloalkoxy, C 6 -C 10  aryl, C 5 -C 10  heteroaryl, C 7 -C 12  aralkyl, C 7 -C 12  heteroaralkyl, C 3 -C 8  heterocyclyl, C 2 -C 12  alkenyl, C 2 -C 12  alkynyl, C 5 -C 10  cycloalkenyl, C 5 -C 10  heterocycloalkenyl, carboxy, carboxylate, cyano, nitro, amino, C 1 -C 6  alkyl amino, C 1 -C 6  dialkyl amino, mercapto, SO 3 H, sulfate, S(O)NH 2 , S(O) 2 NH 2 , phosphate, C 1 -C 4  alkylenedioxy, oxo, acyl, aminocarbonyl, C 1 -C 6  alkyl aminocarbonyl, C 1 -C 6  dialkyl aminocarbonyl, C 1 -C 10  alkoxycarbonyl, C 1 -C 10  thioalkoxycarbonyl, hydrazinocarbonyl, C 1 -C 6  alkyl hydrazinocarbonyl, C 1 -C 6  dialkyl hydrazinocarbonyl, hydroxyaminocarbonyl; or alkoxyaminocarbonyl; and 
         p is 0, 1, or 2. 
       
     
     
         2 . The method of  claim 1 , wherein R 6  is halo, C 1 -C 6  alkyl, C 1 -C 6  haloalkyl or C 1 -C 6  haloalkoxy. 
     
     
         3 . The method of  claim 1 , wherein R 6  is halo or C 1 -C 6  alkyl. 
     
     
         4 . The method of  claim 1 , wherein R 6  is chloro or methyl. 
     
     
         5 . The method of  claim 1 , wherein the compound is 6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxylic acid amide. 
     
     
         6 . The method of  claim 1 , wherein the disease is Huntington's disease, Spinalbulbar Muscular Atrophy (SBMA or Kennedy's Disease) Dentatorubropallidoluysian Atrophy (DRPLA), Spinocerebellar Ataxia 1 (SCA1), Spinocerebellar Ataxia 2 (SCA2), Machado-Joseph Disease (MJD; SCA3), Spinocerebellar Ataxia 6 (SCA6), Spinocerebellar Ataxia 7 (SCA7), or Spinocerebellar Ataxia 12 (SCA12). 
     
     
         7 . The method of  claim 1 , wherein the disease is Huntington's disease. 
     
     
         8 . The method of  claim 1 , wherein the compound is present in a composition comprising a racemic mixture of a compound of formula (XI).