Compounds and therapeutical use thereof

Abstract

Disclosed are 4-arylamino-quinazolines and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

1 . A method of inhibiting tubulin in a mammal in need of such treatment, said method comprises treating the mammal with an effective amount of a compound according to Formula Ia or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 A ring is a 6-membered aryl, heteroaryl or carbocycle;  
 L is [C(R L1 )(R L2 )] n  or —N(R L1 )C(O)—, wherein R L1  and R L2  independently are H or C 1-6  alkyl, n is 0, 1 or 2;  
 R 1  is methyl or ethyl;  
 Ar is aryl or heteroaryl, each of which is optionally substituted by one or more substituents wherein each substituent is independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle;  
 R 2 -R 6 , and R 12 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, with the proviso that when A ring is aryl or heteroaryl, then there are no substituents R 14 -R 17 ; and  
 B, D, Q, T, U and V, are independently C or N, wherein at least one of B and D is nitrogen; wherein when B or D is N, then there is no substituent at the N; and wherein when A ring is heteroaryl and Q, T, U or V is N, then there is no substituent at the N.  
 
   
   
       2 . The method of  claim 1 , wherein said treating step comprises administering to the mammal a pharmaceutical composition comprising said effective amount of said compound.  
   
   
       3 . The method of  claim 1 , wherein B and D are both nitrogen in Formula Ia.  
   
   
       4 . The method of  claim 1 , wherein said compound is according to Formula Ib or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is methyl or ethyl;  
 R 5  is H or F; and  
 R 2 , R 3 , R 4 , R 6 -R 11  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein optionally two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered aryl, heteroaryl, carbocycle, or heterocycle.  
 
   
   
       5 . The method of  claim 1 , wherein said compound is according to Formula Ic or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein, 
 R 1  is methyl or ethyl;  
 R 5  is H or F; and  
 R 2 , R 3 , R 4 , R 6 -R 11  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein optionally two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered aryl, heteroaryl, carbocycle, or heterocycle.  
 
   
   
       6 . The method of  claim 1 , wherein said compound is according to Formula II or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein, 
 R 1  is methyl or ethyl;  
 Ar is aryl or heteroaryl, each of which is optionally substituted by one or more substituents wherein each substituent is independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle;  
 R 5  is H or F;  
 R 2 -R 4 , R 6 , and R 12  and R 13  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; and  
 B, D, Q, T, U and V, are independently C or N, wherein at least one of B and D is N, wherein when B, D, Q, T, U or V is N, then there is not substituent at the N.  
 
   
   
       7 . The method of  claim 1 , wherein said compound is according to Formula III or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein, 
 R 1  is methyl or ethyl;  
 R 2 -R 6  and R 12 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; and  
 B and D are independently C or N, wherein at least one of B and D is N, and when B or D is N, then there is no substituent at the N.  
 
   
   
       8 . The method of  claim 1 , wherein said compound is according to Formula IV or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein, 
 R 1  is methyl or ethyl;  
 A ring is a 6-membered carbocycle, aryl or heteroaryl;  
 R 2 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle, with the proviso that when A ring is aryl or heteroaryl, then there are no substituents R 14 -R 17 ; and  
 B, D, Q, T, U, V, W, X, Y, and Z are independently C or N, wherein at least one of B and D is N; wherein when B, D, W, X, Y, or Z is N, then there is no substituent at the N; and wherein when A is heteroaryl and Q, T, U or V is N, then there is no substituent at the N.  
 
   
   
       9 . The method of  claim 1 , wherein said compound is according to Formula IVa or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is methyl or ethyl;  
 R 2 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle; and  
 B, D, W, X, Y, and Z are independently C or N, provided that at least one of B and D is N, at least one of W, X, Y and Z is N, and when B, D, W, X, Y or Z is N then there is no substituent at the N.  
 
   
   
       10 . The method of  claim 1 , wherein said compound is according to Formula IVb or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein, 
 R 1  is methyl or ethyl;  
 R 2 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, (C 2-6  alkenyl)O—, (C 2-6  alkynyl)O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle; and  
 B and D are independently C or N, provided that at least one of B and D is N, and when B or D is N then there is no substituent at the N.  
 
   
   
       11 . The method of  claim 1 , wherein said compound is according to Formula V or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein, 
 R 1  is methyl or ethyl;  
 R 5  is H, F, Cl, N 3 , methoxy or NH 2 ;  
 R 2 -R 4 , and R 6 -R 13  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle; and  
 B, D, Q, T, U, V, W, X, Y and Z are independently C or N, provided that at least one of B and D is N, and at least one of W, X, Y and Z is N, and wherein when B, D, Q, T, U, V, W, X, Y or Z is N, then there is no substituent at the N.  
 
   
   
       12 . The method of  claim 1 , wherein said compound is according to Formula VI or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is methyl or ethyl;  
 R 5  is H or F;  
 R 2 -R 4 , R 6 -R 13  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle; and  
 B, D, Q, T, U and V are independently C or N, provided that at least one of B and D is N; wherein when B, D, Q, T, U or V is N, then there is no substituent at the N.  
 
   
   
       13 . The method of  claim 1 , wherein said compound is according to Formula VIb or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 R 1  is methyl or ethyl;  
 R 5  is H or F; and  
 R 2 -R 4 , R 6 -R 11  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle.  
 
   
   
       14 . The method of  claim 13 , wherein said treating step comprises administering to the mammal a pharmaceutical composition comprising said effective amount of said compound.  
   
   
       15 . A method of treating fungi infection in a mammal in need of such treatment, said method comprises administering to the mammal a pharmaceutical composition comprising an effective amount of a compound according to Formula Ia or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 A ring is a 6-membered aryl, heteroaryl or carbocycle;  
 L is [C(R L1 )(R L2 )] n  or —N(R L1 )C(O)—, wherein R L1  and R L2  independently are H or C 1-6  alkyl, n is 0, 1 or 2;  
 R 1  is methyl or ethyl;  
 Ar is aryl or heteroaryl, each of which is optionally substituted by one or more substituents wherein each substituent is independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle;  
 R 2 -R 6 , and R 12 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, with the proviso that when A ring is aryl or heteroaryl, then there are no substituents R 14 -R 17 ; and  
 B, D, Q, T, U and V, are independently C or N, wherein at least one of B and D is nitrogen; wherein when B or D is N, then there is no substituent at the N; and wherein when A is heteroaryl and Q, T, U or V is N, then there is no substituent at the N.  
 
   
   
       16 . A method of inhibiting topoisomerase II in a mammal in need of such treatment, said method comprises administering to the mammal a pharmaceutical composition comprising an effective amount of a compound according to Formula Ia or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 A ring is a 6-membered aryl, heteroaryl or carbocycle;  
 L is [C(R L1 )(R L2 )] n  or —N(R L1 )C(O)—, wherein R L1  and R L2  independently are H or C 1-6  alkyl, n is 0, 1 or 2;  
 R 1  is methyl or ethyl;  
 Ar is aryl or heteroaryl, each of which is optionally substituted by one or more substituents wherein each substituent is independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle;  
 R 2 -R 6 , and R 12 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, with the proviso that when A ring is aryl or heteroaryl, then there are no substituents R 14 -R 17 ; and  
 B, D, Q, T, U and V, are independently C or N, wherein at least one of B and D is nitrogen; wherein when B or D is N, then there is no substituent at the N; and wherein when A is heteroaryl and Q, T, U or V is N, then there is no substituent at the N.  
 
   
   
       17 . A method of activating caspase-3 in a mammal in need of such treatment, said method comprises administering to the mammal a pharmaceutical composition comprising an effective amount of a compound according to Formula Ia or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 A ring is a 6-membered aryl, heteroaryl or carbocycle;  
 L is [C(R L1 )(R L2 )] n  or —N(R L1 )C(O)—, wherein R L1  and R L2  independently are H or C 1-6  alkyl, n is 0, 1 or 2;  
 R 1  is methyl or ethyl;  
 Ar is aryl or heteroaryl, each of which is optionally substituted by one or more substituents wherein each substituent is independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle;  
 R 2 -R 6 , and R 12 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, with the proviso that when A ring is aryl or heteroaryl, then there are no substituents R 14 -R 17 ; and  
 B, D, Q, T, U and V, are independently C or N, wherein at least one of B and D is nitrogen; wherein when B or D is N, then there is no substituent at the N; and wherein when A is heteroaryl and Q, T, U or V is N, then there is no substituent at the N.  
 
   
   
       18 . A method of treating a neoplastic disease in a mammal in need of such treatment, said method comprises administering to the mammal a pharmaceutical composition comprising an effective amount of a compound according to Formula IV or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
       R 1  is methyl or ethyl;  
       A ring is a carbocycle, aryl or heteroaryl;  
       R 2 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle, with the proviso that when A ring is aryl or heteroaryl, then there are no substituents R 14 -R 17 ; wherein when A ring is aryl or heteroaryl then R 5  is H or F; and  
       B, D, Q, T, U, V, W, X, Y and Z are independently C or N, wherein at least one of B and D is N; wherein when B, D, W, X, Y or Z is N, then there is no substituent at the N; and wherein when A is heteroaryl and Q, T, U or V is N, then there is no substituent at the N; and  
       with the provisos that: (1) when A is aryl, W, X, Y and Z are all C, and R 9  is H then at least one of R 8  and R 10  is not H or halo; and  
       (2) when A is heteroaryl, W, X, Y and Z are all C, and R 9  is H, then at least one of R 8  and R 10  is not H, halo or C 1-6  alkyl.  
     
   
   
       19 . The method of  claim 18 , further comprising administering to the mammal another anti-cancer agent selected from the group consisting of alkylating agents, antimitotic agents, topo I inhibitors, topo II inhibitors, RNA/DNA antimetabolites, EGFR inhibitors, angiogenesis inhibitors, melphalan, chlorambucil, cyclophosamide, ifosfamide, vincristine, mitoguazone, epirubicin, aclarubicin, bleomycin, mitoxantrone, elliptinium, fludarabine, ocreotide, retinoic acid, tamoxifen, Gleevec®(Imatinib Mesylate) and alanosine.  
   
   
       20 . A method of treating cancer in a patient who has been treated with and is not responsive to another anti-cancer drug or has developed resistance to such other anti-cancer compound, said method comprises administering to the mammal a pharmaceutical composition comprising an effective amount of a compound of Formula IV according to  claim 18 , or a pharmaceutically acceptable salt or solvate thereof.  
   
   
       21 . A compound represented by Formula IVa:  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt or solvate thereof, wherein: 
 R 1  is methyl or ethyl;  
 R 2 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle; and  
 B, D, W, X, Y, and Z are independently C or N, provided that at least one of B and D is N, at least one of W, X, Y and Z is N, and when B, D, W, X, Y or Z is N then there is no substituent at the N.  
 
   
   
       22 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound according to  claim 21 .  
   
   
       23 . The compound of  claim 21 , wherein said compound is represented by  
     
       
         
         
             
             
         
       
     
     or pharmaceutically acceptable salt or solvate thereof, wherein: 
 R 1  is methyl or ethyl;  
 R 2 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, (C 2-6  alkenyl)O—, (C 2-6  alkynyl)O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle; and  
 B and D are independently C or N, provided that at least one of B and D is N, and when B or D is N then there is no substituent at the N; with the proviso that said compound is not 2-amino-4-(N-ethylanilino)-5,6,7,8-tetrahydro-quinazoline.  
 
   
   
       24 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound according to  claim 23 .  
   
   
       25 . A compound represented by Formula V:  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt or solvate thereof, wherein: 
 R 1  is methyl or ethyl;  
 R 5  is H, F, Cl, N 3 , methyl, methoxy or NH 2 , with the proviso that when R 5  is methoxy, then R 1  is methyl;  
 R 2 -R 4 , and R 6 -R 13  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle; and  
 B, D, Q, T, U, V, W, X, Y and Z are independently C or N, provided that at least one of B and D is N, and at least one of W, X, Y and Z is N, and wherein when B, D, Q, T, U, V, W, X, Y or Z is N, then there is no substituent at the N.  
 
   
   
       26 . A pharmaceutical composition comprising a pharmaceutically acceptable carrier and an effective amount of a compound of  claim 25 .  
   
   
       27 . The compound of  claim 25 , wherein said compound is selected from the group consisting of: 
 (2-Chloro-quinazolin-4-yl)-(6-methoxy-pyridin-3-yl)-methyl-amine;    N 2 -(2-Hydroxyethyl)-N 4 -(6-methoxypyridin-3-yl)-N 4 -methyl-quinazoline-2,4-diamine;    N 4 -(6-Methoxypyridin-3-yl)-N 4 -methyl-quinazoline-2,4-diamine;    (2-Methyl-quinazolin-4-yl)-(6-methoxy-pyridin-3-yl)-methyl-amine;    (6-Methoxy-pyridazin-3-yl)-(2-methyl-quinazolin-4-yl)-methyl-amine;    (5-Methoxy-pyrazin-2-yl)-(2-methyl-quinazolin-4-yl)-methyl-amine;    (2-Dimethylamino-quinazolin-4-yl)-(6-methoxy-pyridin-3-yl)-methyl-amine;    (2-Methylamino-quinazolin-4-yl)-(6-methoxy-pyridin-3-yl)-methyl-amine;    (2-Methyl-quinazolin-4-yl)-(pyrazin-2-yl)-methyl-amine;    (5-Methoxy-pyridin-2-yl)-(2-methyl-quinazolin-4-yl)-methyl-amine; and    (5-Methoxy-pyrimidin-2-yl)-(2-methyl-quinazolin-4-yl)-methyl-amine; 
 or a pharmaceutically acceptable salt or solvate thereof.  
   
   
   
       28 . The compound of  claim 25 , wherein said compound is represented by Formula VIa  
     
       
         
         
             
             
         
       
     
     or a pharmaceutically acceptable salt or solvate thereof, wherein: 
 R 1  is methyl or ethyl;  
 R 5  is H or F;  
 R 2 -R 4 , R 6 -R 11  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, wherein optionally any two adjacent R 7 -R 11  groups together form a 3, 4, 5 or 6-membered carbocycle or heterocycle; and  
 Q, T, U and V are independently C or N, wherein at least one of Q, T, U and V is N, and when Q, T, U or V is N there is no substituent at the N, provided that when R 9  is H then at least one of R 8  and R 10  is not H or alkyl.  
 
   
   
       29 . The compound of  claim 28 , wherein said compound is selected from the group consisting of: 
 (4-Methoxy-phenyl)-(2-methyl-pyrido[2,3-d]pyrimidin-4-yl)-methyl-amine; and    (4-Methoxy-phenyl)-(2-methyl-pteridin-4-yl)-methyl-amine; 
 or a pharmaceutically acceptable salt or solvate thereof.  
   
   
   
       30 . A method of inducing apoptosis in a mammal in need of such treatment, said method comprises administering to the mammal a pharmaceutical composition comprising an effective amount of a compound according to Formula Ia or a pharmaceutically acceptable salt or solvate thereof:  
     
       
         
         
             
             
         
       
     
     wherein: 
 A ring is a 6-membered aryl, heteroaryl or carbocycle;  
 L is [C(R L1 )(R L2 )] n  or —N(R L1 )C(O)—, wherein R L1  and R L2  independently are H or C 1-6  alkyl, n is 0, 1 or 2;  
 R 1  is methyl or ethyl;  
 Ar is aryl or heteroaryl, each of which is optionally substituted by one or more substituents wherein each substituent is independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle;  
 R 2 -R 6 , and R 12 -R 17  are independently H, halo, N 3 , OH, thiol, nitro, CN, NH 2 , C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, halo-C 1-6  alkyl, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, 3, 4, 5, or 6-membered carbocycle, heterocycle, aryl, or heteroaryl, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl, or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle; wherein any of the groups is optionally substituted with 1-3 substituents wherein each substituent is independently halo, N 3 , OH, thiol, nitro, CN, C 1-6  alkyl, C 2-6  alkenyl, C 2-6  alkynyl, C 1-6  alkoxy, C 1-6  alkylthiol, C 2-6  alkenyl-O—, C 2-6  alkynyl-O—, hydroxy-C 1-6  alkyl, C 1-6  alkoxy-C 1-6  alkyl, C 1-6  acyl, C 1-6  acyloxy, —C 1-6  alkyl-C(O)O—C 1-6  alkyl, —C(O)O—C 1-6  alkyl, C 1-6  alkyl-C(O)O—C 1-6  alkyl-, C 1-6  acylamido, —N(R a )(R b ), —C 1-6  alkyl-C(O)N(R a )(R b ), —C(O)N(R a )(R b ), N(R a )(R b )—C 1-6  alkyl-, wherein R a  and R b  are independently H, OH (R a  and R b  are not both OH), C 2-6  hydroxyalkyl, or C 1-6  alkyl or R a  and R b  together with the nitrogen atom to which they are both linked form a 3, 4, 5 or 6-membered heterocycle, with the proviso that when A ring is aryl or heteroaryl, then there are no substituents R 14 -R 17 ; and  
 B, D, Q, T, U and V, are independently C or N, wherein at least one of B and D is nitrogen; wherein when B or D is N, then there is no substituent at the N; and wherein when A is heteroaryl and Q, T, U or V is N, then there is no substituent at the N.