Novel IDO Inhibitors and Methods of Use Thereof

Abstract

Novel indoleamine 2,3-dioxygenase (IDO) inhibitors, compositions comprising the same, and methods of use thereof are disclosed.

1 . A compound having indoleamine 2,3 dioxygenase (IDO) inhibitory activity, said compound having the formula of: 
     
       
         
         
             
             
         
       
     
     wherein R 1  is cycloalkyl or aryl; R 2  is alkenyl or —CH 2 —R 4 , wherein R 4  is hydrogen or aryl; and n is 2 or 3; wherein when n is 2, R 1  is selected from the group consisting of cycloalkyl, bicyclic aryl, heteroaryl, and a substituted aryl, wherein the substituent is selected from the group consisting of alkyl, halo, haloalkyl, alkylthio, hydroxyl, carboxyl, oxo, epoxy, alkyloxycarbonyl, alkylcarbonyloxy, amino, carbamoyl, urea, alkylurea, and thiol. 
   
   
       2 . The compound of  claim 1 , wherein R 4  is selected from the group consisting of phenyl, naphthyl, and pyridyl. 
   
   
       3 . The compound of  claim 1 , wherein when n is 2, R 1  is selected from the group consisting of indolyl, naphthyl, indanyl and adamantyl. 
   
   
       4 . The compound of  claim 1  which is N-Phenethyl-S-methyl-dithiocarbamate or N-4-Fluorophenethyl-S-methyl-dithiocarbamate. 
   
   
       5 . (canceled) 
   
   
       6 . (canceled) 
   
   
       7 . A composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier medium. 
   
   
       8 - 12 . (canceled) 
   
   
       13 . The composition of  claim 7  further comprising at least one signal transduction inhibitor (STI). 
   
   
       14 - 20 . (canceled) 
   
   
       21 . The composition of  claim 7  further comprising at least one chemotherapeutic agent. 
   
   
       22 . (canceled) 
   
   
       23 . The composition of  claim 21 , wherein said at least one chemotherapeutic agent is selected from the group consisting of paclitaxel, cisplatin, docetaxol, carboplatin, vincristine, vinblastine, methotrexate, cyclophosphamide, CPT-11, 5-fluorouracil (5-FU), gemcitabine, estramustine, carmustine, adriamycin (doxorubicin), etoposide, arsenic trioxide, irinotecan, and epothilone derivatives. 
   
   
       24 . The compound of  claim 1 , wherein when n is 3, R 1  is selected from the group consisting of indolyl, phenyl, naphthyl, indanyl and adamantyl.