Mitotic kinesin inhibitors

Abstract

The present invention relates to compounds that are useful for treating cellular proliferative diseases, for treating disorders mediated, at least in part, by KSP, and for inhibiting KSP. The invention also related to pharmaceutical compositions comprising such compounds, methods of treating cancer by the administration of such compositions, and processes for the preparation of the compounds. Compounds of the invention have the following formula:

1 . A compound of formula I: 
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, 
     wherein:
 R 1  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, heterocyclyl, halo, cyano, nitro, carboxy, hydroxy, alkoxy, aryloxy, heterocyclyloxy, aminocarbonyl, aminocarbonyloxy, alkylcarbonyloxy, arylcarbonyloxy, heterocyclylcarbonyloxy, alkoxycarbonyl, aryloxycarbonyl, heterocyclyloxycarbonyl, amino, alkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, alkoxycarbonylamino, aryloxycarbonylamino, heterocyclyloxycarbonylamino, alkylsulfonylamino, arylsulfonylamino, heterocyclylsulfonylamino, aminosulfonyl, alkylsulfonyl, arylsulfonyl, and heterocyclylsulfonyl; 
 R 2  is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, aryl, heterocyclyl, carboxy, alkoxycarbonyl, aryloxycarbonyl, heterocyclyloxycarbonyl, and aminocarbonyl; 
 R 3  is selected from the group consisting of alkyl, alkenyl, alkynyl, aryl, and heterocyclyl, or 
 R 2  and R 3 , together with the carbon atom to which they are attached can form a carbocyclic or heterocyclic ring, having from 3 to 8 ring atoms, wherein from 1 to 3 ring atoms of the heterocyclic ring are selected from the group consisting of N, O and S; 
 R 4  is selected from the group consisting of hydrogen, alkyl, aryl, and heterocyclyl; 
 R 5  is selected from the group consisting of hydrogen, alkyl, aryl, heterocyclyl, alkoxycarbonyl, aryloxycarbonyl, heterocyclyloxycarbonyl, aminocarbonyl, alkylcarbonyl, arylcarbonyl, heterocyclylcarbonyl, alkylsulfonyl, arylsulfonyl, and heterocyclylsulfonyl; 
 R 6  is selected from the group consisting of hydrogen, alkyl, aryl, heterocyclyl, hydroxy, alkoxy, aryloxy, heterocyclyloxy, amino, alkylsulfonyl, arylsulfonyl, and heterocyclylsulfonyl, alkylcarbonyloxy, arylcarbonyloxy, heterocyclylcarbonyloxy, alkoxycarbonyl, aryloxycarbonyl, heterocyclyloxycarbonyl, alkoxycarbonylamino, aryloxycarbonylamino, heterocyclyloxycarbonylamino, alkylcarbonylamino, arylcarbonylamino, heterocyclylcarbonylamino, aminocarbonyloxy, alkylsulfonylamino, arylsulfonylamino, heterocyclylsulfonylamino, and aminosulfonyl; and 
 R 7  is selected from the group consisting of hydrogen, alkyl, aryl, and heterocyclyl, or 
 R 6  and R 7   3  can be taken together with the atoms to which they are attached to form a heterocyclic ring, having 5 to 8 ring atoms, wherein from 1 to 3 ring atoms of the heterocyclic ring are selected from the group consisting of N, O and S. 
 
   
   
       2 - 45 . (canceled)