US2006079512A1PendingUtilityA1

Dibenzodiazepinone analogues, processes for their production and their use as pharmaceuticals

55
Assignee: ECOPIA BIOSCIENCES INCPriority: Jan 21, 2003Filed: Oct 20, 2005Published: Apr 13, 2006
Est. expiryJan 21, 2023(expired)· nominal 20-yr term from priority
A61P 31/04A61P 35/00C12N 9/0004C07D 243/38C12N 9/14C12P 17/10A61P 29/00C12N 15/52C12N 9/90C12N 9/88C12N 9/93C07D 405/06A61K 38/00C12N 9/10C07D 405/14C12N 9/12C12R 2001/29C12N 1/205Y02A50/30
55
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Claims

Abstract

The invention relates to biologically active dibenzodiazepinone analogs represented by Formula I, to methods of producing them, to pharmaceutical compositions comprising them and to methods of treating neoplastic conditions.

Claims

exact text as granted — not AI-modified
1 . A compound of Formula I:  
       
         
           
           
               
               
           
         
       
       wherein, 
 W 1 , W 2  and W 3  are each independently selected from  
                     
 the chain from the tricycle terminates at W 3 , W 2  or W 1  with W 3 , W 2  or W 1  respectively being either —CH═O, —CH(OC 1-6 alkyl) 2 , —CH 2 OH, —CH 2 OC 1-6 alkyl or C(O)OR 7 ;  
 R 1  is selected from H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, C 5-10 heteroaryl, C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C(O)H, C(O)C 1-10 alkyl, C(O)C 2-10 alkenyl, C(O)C 2-10 alkynyl, C(O)C 6-10 aryl, C(O)C 5-10 heteroaryl, C(O)C 3-10 cycloalkyl; C(O)C 3-10 heterocycloalkyl or a C-coupled amino acid;  
 R 2 , R 3 , and R 4  are each independently selected from H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, C 5-10 heteroaryl, C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C(O)H, C(O)C 1-10 alkyl, C(O)C 2-10 alkenyl, C(O)C 2-10 alkynyl, C(O)C 6-10 aryl, C(O)C 5-10 heteroaryl, C(O)C 3-10 cycloalkyl; C(O)C 3-10 heterocycloalkyl or a C-coupled amino acid;  
 R 5  and R 6  are each independently selected from H, OH, OC 1-6 alkyl, OC(O)C 1-6 alkyl, NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , NHC(O)C 1-6 alkyl;  
 R 7  is selected from H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, C 5-10 heteroaryl, C 3-10 cycloalkyl and C 3-10 heterocycloalkyl;  
 X 1 , X 2 , X 3 , X 4  and X 5  are each H; or  
 one of X 1 , X 2 , X 3 , X 4  or X 5  is halogen and the remaining ones are H; and  
 wherein, when any of R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and R 7  comprises an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, then the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group is optionally substituted with substituents selected from acyl, amino, acylamino, acyloxy, carboalkoxy, carboxy, carboxyamido, cyano, halo, hydroxyl, nitro, thio, C 1-6 alkyl, C 2-7 alkenyl, C 2-7 alkynyl, C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C 6-10 aryl, C 5-10 heteroaryl, alkoxy, aryloxy, sulfinyl, sulfonyl, oxo, guanidino and formyl;  
 with the proviso that when W 1 , W 2  and W 3  are all —CH═C(CH 3 ), X 1 , X 2 , X 3 , X 4  and X 5  are all H, and R 2 , R 3  and R 4  are all H, then R 1  is not H;  
 with the proviso that when W 1 , W 2  and W 3  are all —CH═C(CH 3 ), X 1 , X 2 , X 3 , X 4  and X 5  are all H, and R 1  is H, then R 2 , R 3  and R 4  are not all CH 3  or all C(O)CH 3 ;  
 with the proviso that when the chain from the tricycle terminates at W 1  or W 2  with W 2  or W 1  respectively being either —CH═O, —CH(QC 1-6 alkyl) 2 , —CH 2 OH, —CH 2 OC 1-6 alkyl or C(O)OR 7 , then R 1  is H;  
 and an ester, ether, N-alkylated or N-acylated derivative, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
 
     
     
         2 . A compound of Formula II:  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 1  is a linear C 1-10 alkyl;  
 or a farnesyl derivative thereof, wherein said farnesyl derivative has one, two or three hydrogenated or hydroalkoxylated double bonds;  
 or a pharmaceutically acceptable salt or prodrug thereof.  
 
     
     
         3 . A compound of Formula III:  
       
         
           
           
               
               
           
         
       
       wherein, 
 W 1 , W 2  and are each independently selected from  
                     
 the chain from the tricycle terminates at W 3 , W 2  or W 1  with W 3 , W 2  or W 1  respectively being either —CH═O, —CH(OC 1-6 alkyl) 2 , —CH 2 OH, —CH 2 OC 1-6 alkyl or C(O)OR 7 ;  
 R 1  is selected from H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, C 5-10 heteroaryl, C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C(O)H, C(O)C 1-10 alkyl, C(O)C 2-10 alkenyl, C(O)C 2-10 alkynyl, C(O)C 6-10 aryl, C(O)C 5-10 heteroaryl, C(O)C 3-10 cycloalkyl; C(O)C 3-10 -heterocycloalkyl or a C-coupled amino acid;  
 R 2 , R 3 , and R 4  are each independently selected from H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, C 5-10 heteroaryl, C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C(O)H, C(O)C 1-10 alkyl, C(O)C 2-10 alkenyl, C(O)C 2-10 alkynyl, C(O)C 6-10 aryl, C(O)C 5-10 heteroaryl, C(O)C 3-10 cycloalkyl; C(O)C 3-10 heterocycloalkyl or a C-coupled amino acid;  
 R 5  and R 6  are each independently selected from H, OH, OC 1-6 alkyl, NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , NHC(O)C 1-6 alkyl;  
 R 7  is selected from H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, C 5-10 heteroaryl, C 3-10 cycloalkyl and C 3-10 heterocycloalkyl;  
 X 1 , X 2 , X 3 , X 4  and X 5  are each H; or  
 one of X 1 , X 2 , X 3 , X 4  or X 5  is halogen and the remaining ones are H; and  
 wherein, when any of R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and R 7  comprises an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, then the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group is optionally substituted with substituents selected from acyl, amino, acylamino, acyloxy, carboalkoxy, carboxy, carboxyamido, cyano, halo, hydroxyl, nitro, thio, C 1-6 alkyl, C 2-7 alkenyl, C 2-7 alkynyl, C 3-10  cycloalkyl, C 3-10 heterocycloalkyl, C 6-10 aryl, C 5-10 heteroaryl, alkoxy, aryloxy, sulfinyl, sulfonyl, oxo, guanidino and formyl;  
 and an ester, ether, N-alkylated or N-acylated derivative, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
 
     
     
         4 . The compound of  claim 3 , wherein said compound is a compound of Formula IV:  
       
         
           
           
               
               
           
         
       
       wherein, 
 W 1 , W 2  and W 3  are each independently selected from  
                     
 the chain from the tricycle terminates at W 3 , W 2  or W 1  with W 3 , W 2  or W 1  respectively being either —CH═O, —CH(OC 1-6 alkyl) 2 , —CH 2 OH, —CH 2 OC 1-6 alkyl or C(O)OR 7 ;  
 R 1  is selected from H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, C 5-10 heteroaryl, C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C(O)H, C(O)C 1-10 alkyl, C(O)C 2-10 alkenyl, C(O)C 2-10 alkynyl, C(O)C 6-10 aryl, C(O)C 5-10 heteroaryl, C(O)C 3-10 cycloalkyl;  
 C(O)C 3-10 heterocycloalkyl or a C-coupled amino acid;  
 R 2 , R 3 , and R 4  are each independently selected from H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, C 5-10 heteroaryl, C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C(O)H, C(O)C 1-10 alkyl, C(O)C 2-10 alkenyl, C(O)C 2-10 alkynyl, C(O)C 6-10 aryl, C(O)C 5-10 heteroaryl, C(O)C 3-10 cycloalkyl; C(O)C 3-10 heterocycloalkyl or a C-coupled amino acid;  
 R 5  and R 6  are each independently selected from H, OH, OC 1-6 alkyl, OC(O)C 1-6 alkyl, NH 2 , NHC 1-6 alkyl, N(C 1-6 alkyl) 2 , NHC(O)C 1-6 alkyl;  
 R 7  is selected from H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, C 5-10  heteroaryl, C 3-10 cycloalkyl and C 3-10 heterocycloalkyl;  
 X 1 , X 2 , X 3 , X 4  and X 5  are each H; or  
 one of X 1 , X 2 , X 3 , X 4  or X 5  is halogen and the remaining ones are H; and  
 wherein, when any of R 1 , R 2 , R 3 , R 4 , R 5 , R 6  and R 7  comprises an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, then the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group is optionally substituted with substituents selected from acyl, amino, acylamino, acyloxy, carboalkoxy, carboxy, carboxyamido, cyano, halo, hydroxyl, nitro, thio, C 1-6 alkyl, C 2-7 alkenyl, C 2-7 alkynyl, C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C 6-10 aryl, C 5-10 heteroaryl, alkoxy, aryloxy, sulfinyl, sulfonyl, oxo, guanidino and formyl;  
 with the proviso that when W 1 , W 2  and W 3  are all —CH═C(CH 3 ), X 1 , X 2 , X 3 , X 4  and X 5  are all H, and R 2 , R 3  and R 4  are all H, then R 1  is not H;  
 with the proviso that when the chain from the tricycle terminates at W 1  or W 2  with W 2  or W 1  respectively being either —CH═O, —CH(OC 1-6 alkyl) 2 , —CH 2 OH, —CH 2 OC 1-6 alkyl or C(O)OR 7 , then R 1  is H;  
 and an ester, ether, N-alkylated or N-acylated derivative, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
 
     
     
         5 . The compound of  claim 3 , wherein said compound is a compound of Formula V:  
       
         
           
           
               
               
           
         
       
       wherein, 
 W 1 , W 2  and W 3  are each independently selected from  
                     
 the chain from the tricycle terminates at W 3 , W 2  or W 1  with W 3 , W 2  or W 1  respectively being either —CH═O or —CH 2 OH;  
 R 1  is selected from H, C 1 -oalkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, C 5-10 heteroaryl, C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C(O)C 1-10 alkyl, C(O)C 2-10 alkenyl, C(O)C 2-10 alkynyl, C(O)C 6-10 aryl, C(O)C 5-10 heteroaryl, C(O)C 3-10 cycloalkyl; C(O)C 3-10 heterocycloalkyl or a C-coupled amino acid;  
 R 2 , R 3 , and R 4  are each independently selected from H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 6-10 aryl, C 5-10 heteroaryl, C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C(O)H, C(O)C 1-10 alkyl, C(O)C 2-10 alkenyl, C(O)C 2-10 alkynyl, C(O)C 6-10 aryl, C(O)C 5-10 heteroaryl, C(O)C 3-10 cycloalkyl; C(O)C 3-10 heterocycloalkyl or a C-coupled amino acid;  
 R 5  and R 6  are each independently selected from H, OH and OC 1-6 alkyl;  
 wherein, when any of R 1 , R 2 , R 3 , R 4 , R 5  and R 6  comprises an alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group, then the alkyl, alkenyl, alkynyl, aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group is optionally substituted with substituents selected from acyl, amino, acylamino, acyloxy, carboalkoxy, carboxy, carboxyamido, cyano, halo, hydroxyl, nitro, thio, C 1-6 alkyl, C 2-7 alkenyl, C 2-7 alkynyl, C 3-10 cycloalkyl, C 3-10 heterocycloalkyl, C 6-10 aryl, C 5-10 heteroaryl, alkoxy, aryloxy, sulfinyl, sulfonyl, oxo, guanidino and formyl; and  
 with the proviso that when W 1 , W 2  and W 3  are all —CH═C(CH 3 ), and R 2 , R 3  and R 4  are all H, then R 1  is not H;  
 or a pharmaceutically acceptable salt or prodrug thereof.  
 
     
     
         6 . The compound of  claim 3 , wherein said compound is a compound of Formula VI:  
       
         
           
           
               
               
           
         
       
       wherein, 
 W 1 , W 2  and W 3  is each independently selected from  
                     
 the chain from the tricycle may terminate at W 3 , W 2  or W 1  with W 3 , W 2  or W 1  respectively being either —CH═O or —CH 2 OH;  
 A is selected from —NH—, —NCH 2 R 8 , —NC(O)R 8 ;  
 R 8  is selected from H, C 1-6 alkyl, C 2-6 alkene, aryl or heteroaryl;  
 R 2 , R 3 , and R 4  are each independently selected from H, R 5 , —C(O)R 6    
 R 5  is selected from C 1-6 alkyl, C 2-7 alkalene, aryl or heteroaryl;  
 R 6  is selected from H, C 1-6 alkyl, C 2-7 alkalene, aryl or heteroaryl;  
 or a pharmaceutically acceptable salt or prodrug thereof.  
 
     
     
         7 . The compound of  claim 6 , wherein said compound is a compound of Formula VII:  
       
         
           
           
               
               
           
         
       
       wherein, 
 W 1 , W 2  and W 3  is each independently selected from  
                     
 the chain from the tricycle may terminate at W 3 , W 2  or W 1  with W 3 , W 2  or W 1  respectively being either —CH═O or —CH 2 OH;  
 A is selected from —NH—, —NCH 2 R 8 , —NC(O)R 8 ;  
 R 8  is selected from C 1-6 alkyl, C 2-6 alkene, aryl or heteroaryl;  
 R 2 , R 3 , and R 4  are each independently selected from H, R 5 , —C(O)R 6    
 R 5  is selected from C 1-6 alkyl, C 2-7 alkalene, aryl or heteroaryl;  
 R 6  is selected from H, C 1-6 alkyl, C 2-7 alkalene, aryl or heteroaryl;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         8 . The compound of  claim 6 , wherein said compound is a compound of Formula VIII:  
       
         
           
           
               
               
           
         
         Formula VIII  
         wherein,  
         W 1 , W 2  and W 3  is each independently selected from  
         
           
             
             
                 
                 
             
           
         
         A is selected from —NH—, —NCH 2 R 8 , —NC(O)R 8 ;  
         R 8  is selected from H, C 1-6 alkyl, C 2-6 alkene, aryl or heteroaryl;  
         R 2 , R 3 , and R 4  are each independently selected from H, R 5 , —C(O)R 6    
         R 5  is selected from C 1-6 alkyl, C 2-7 alkalene, aryl or heteroaryl;  
         R 6  is selected from H. C 1-6 alkyl, C 2-7 alkalene, aryl or heteroaryl;  
         or a pharmaceutically acceptable salt or prodrug thereof.  
       
     
     
         9 . The compound of  claim 7 , wherein said compound is a compound of Formula IX:  
       
         
           
           
               
               
           
         
       
       wherein, 
 W 1 , W 2  and W 3  is each independently selected from  
                     
 A is selected from —NH—, —NCH 2 R 8 , —NC(O)R 8 ;  
 R 8  is selected from C 1-6 alkyl, C 2-6 alkene, aryl or heteroaryl;  
 R 2 , R 3 , and R 4  are each independently selected from H, R 5 , —C(O)R 6    
 R 5  is selected from C 1-6 alkyl, C 2-7 alkalene, aryl or heteroaryl;  
 R 6  is selected from H, C 1-6 alkyl, C 2-7 alkalene, aryl or heteroaryl;  
 or a pharmaceutically acceptable salt thereof.  
 
     
     
         10 . The compound of  claim 1 , wherein R 1  is a C 1-10 alkyl, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         11 . The compound of  claim 1 , wherein one of W 1 , W 2  and W 3  is —CH═C(CH 3 )—, and the remaining ones are —CH 2 CH(CH 3 )—, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         12 . The compound of  claim 1 , wherein two of W 1 , W 2  and W 3  are —CH═C(CH 3 )—, and the remaining one is —CH 2 CH(CH 3 )—, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         13 . The compound of  claim 1 , wherein W 1 , W 2  and W 3  are each —CH 2 CH(CH 3 )—, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         14 . The compound of  claim 1 , wherein R 1  is a C 1-10 alkyl, and W 1 , W 2  and W 3  are each —CH 2 CH(CH 3 )—, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         15 . The compound of  claim 1 , wherein X 1  is a bromide, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         16 . The compound of  claim 1 , wherein R 1  is a linear C 1-10 alkyl, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         17 . The compound of  claim 1 , wherein R 1  is a linear C 1-6 alkyl, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         18 . The compound of  claim 1 , wherein R 1  is methyl, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         19 . The compound of  claim 1 , wherein R 1  is ethyl, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         20 . The compound of  claim 1 , wherein R 1  is n-propyl, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         21 . The compound of  claim 1 , wherein R 1  is n-butyl, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         22 . The compound of  claim 1 , wherein R 1  is n-hexyl, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         23 . The compound of  claim 1 , wherein said compound is selected from Compounds 2 to 7, 9 to 11 and 13 to 130, or a pharmaceutically acceptable salt, solvate or prodrug thereof:  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         24 . The compound of  claim 23 , wherein said compound is selected from Compounds 1 to 7, 9 to 11, 14, 17, 18, 46, 63, 64, 67, 77, 78, 80, 82 to 85, 87, 89, 92, 95 to 98,100 to 103, 105, 107 and 108, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         25 . The compound of  claim 23 , wherein said compound is selected from Compounds 2, 14, 62, 63, 64, 67, 68, 69, 70, 72, 78, 79, 80, 81, 85, 86, 87, and 98 to 100, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         26 . The compound of  claim 25 , wherein said compound is selected from Compounds 2, 14, 63, 64, 67, 78, 80, 85, 87, 98, and 100, or a pharmaceutically acceptable salt, solvate or prodrug thereof.  
     
     
         27 . The compound of  claim 23 , wherein said compound is selected from Compounds 40-46, and 97.  
     
     
         28 . A process for producing a compound of  claim 1 , said process-comprising chemically modifying Compound 1:  
       
         
           
           
               
               
           
         
       
       wherein said chemical modification comprises at least one step selected from the group consisting of: N-alkylations, N-acylations, O-alkylations, O-acylations, aromatic halogenation, farnesyl hydrogenation, farnesyl epoxidation, farnesyl dihydroxylation, farnesyl hydration, farnesyl hydroalkoxylation, farnesyl hydroamidation, and farnesyl ozonolysis.  
     
     
         29 . The process of  claim 28 , wherein said chemical modification comprises at least one step selected from the group consisting of: N-alkylations, O-acylations, farnesyl hydrogenation, and farnesyl hydroalkoxylation.  
     
     
         30 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 1  and a pharmaceutically acceptable carrier.  
     
     
         31 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 2  and a pharmaceutically acceptable carrier.  
     
     
         32 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 23  and a pharmaceutically acceptable carrier.  
     
     
         33 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 24  and a pharmaceutically acceptable carrier.  
     
     
         34 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 25  and a pharmaceutically acceptable carrier.  
     
     
         35 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 26  and a pharmaceutically acceptable carrier.  
     
     
         36 . A pharmaceutical composition comprising a therapeutically effective amount of a compound of  claim 27  and a pharmaceutically acceptable carrier.  
     
     
         37 . A method of inhibiting the growth of a neoplastic cell, comprising contacting said neoplastic cell with a compound of  claim 1 , such that growth of said neoplastic cell is inhibited.  
     
     
         38 . A method of inhibiting the growth of a neoplastic cell, comprising contacting said neoplastic cell with a compound of  claim 2 , such that growth of said neoplastic cell is inhibited.  
     
     
         39 . A method of inhibiting the growth of a neoplastic cell, comprising contacting said neoplastic cell with a compound of  claim 23 , such that growth of said neoplastic cell is inhibited.  
     
     
         40 . A method of inhibiting the growth of a neoplastic cell, comprising contacting said neoplastic cell with a compound of  claim 24 , such that growth of said neoplastic cell is inhibited.  
     
     
         41 . A method of inhibiting the growth of a neoplastic cell, comprising contacting said neoplastic cell with a compound of  claim 25 , such that growth of said neoplastic cell is inhibited.  
     
     
         42 . A method of inhibiting the growth of a neoplastic cell, comprising contacting said neoplastic cell with a compound of  claim 26 , such that growth of said neoplastic cell is inhibited.  
     
     
         43 . A method of inhibiting the growth of a neoplastic cell, comprising contacting said neoplastic cell with a compound of  claim 27 , such that growth of said neoplastic cell is inhibited.  
     
     
         44 . A method of treating a neoplastic condition in a subject, comprising administering a therapeutically effective amount of a compound of  claim 1  to said subject, such that the neoplastic condition is treated.  
     
     
         45 . A method of treating a neoplastic condition in a subject, comprising administering a therapeutically effective amount of a compound of  claim 2  to said subject, such that the neoplastic condition is treated.  
     
     
         46 . A method of treating a neoplastic condition in a subject, comprising administering a therapeutically effective amount of a compound of  claim 23  to said subject, such that the neoplastic condition is treated.  
     
     
         47 . A method of treating a neoplastic condition in a subject, comprising administering a therapeutically effective amount of a compound of  claim 24  to said subject, such that the neoplastic condition is treated.  
     
     
         48 . A method of treating a neoplastic condition in a subject, comprising administering a therapeutically effective amount of a compound of  claim 25  to said subject, such that the neoplastic condition is treated.  
     
     
         49 . A method of treating a neoplastic condition in a subject, comprising administering a therapeutically effective amount of a compound of  claim 26  to said subject, such that the neoplastic condition is treated.  
     
     
         50 . A method of treating a neoplastic condition in a subject, comprising administering a therapeutically effective amount of a compound of  claim 27  to said subject, such that the neoplastic condition is treated.  
     
     
         51 . A method of treating a neoplastic condition in a mammal, comprising administering a therapeutically effective amount of a compound of  claim 1  to said mammal, such that the neoplastic condition is treated.  
     
     
         52 . A method of treating a neoplastic condition in a mammal, comprising administering a therapeutically effective amount of a compound of  claim 2  to said mammal, such that the neoplastic condition is treated.  
     
     
         53 . A method of treating a neoplastic condition in a mammal, comprising administering a therapeutically effective amount of a compound of  claim 23  to said mammal, such that the neoplastic condition is treated.  
     
     
         54 . A method of treating a neoplastic condition in a mammal, comprising administering a therapeutically effective amount of a compound of  claim 24  to said mammal, such that the neoplastic condition is treated.  
     
     
         55 . A method of treating a neoplastic condition in a mammal, comprising administering a therapeutically effective amount of a compound of  claim 25  to said mammal, such that the neoplastic condition is treated.  
     
     
         56 . A method of treating a neoplastic condition in a mammal, comprising administering a therapeutically effective amount of a compound of  claim 26  to said mammal, such that the neoplastic condition is treated.  
     
     
         57 . A method of treating a neoplastic condition in a mammal, comprising administering a therapeutically effective amount of a compound of  claim 27  to said mammal, such that the neoplastic condition is treated.

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