Building block forming a c-c or a c-hetero atom bond uponreaction

Abstract

A building block having the dual capabilities of transferring genetic information and functional entity precursor to a recipient reactive group is disclosed. The building block may be used in the generation of a single complex or libraries of different complexes, wherein the complex comprises an encoded molecule linked to an encoding element. Libraries of complexes are useful in the quest for pharmaceutically active compounds.

1 . A building block of the general formula 
       Complementing Element-Linker-Carrier-C—F-connecting group—Functional entity precursor capable of transferring a Functional entity precursor to a recipient reactive group, wherein 
 Complementing Element is a group identifying the Functional entity precursor,  
 Linker is a chemical moiety comprising a spacer and a S—C-connecting group, wherein the spacer is a valence bond or a group distancing the Functional entity precursor to be transferred from the complementing element and the S—C-connecting group connects the spacer with the Carrier,  
 Carrier is arylene, heteroarylene, C 1 -C 6  alkylene, C 1 -C 6  alkenylene, C 1 -C 6  alkynylene, or —(CF 2 ) m — substituted with 0-3 R 1  wherein m is an integer between 1 and 10;  
   R 1  are independently selected from the group consisting of —H, —OR 2 , —NR 2   2 , -Halogen, —NO 2 , —CN, —C(Halogen) 3 , —C(O)R 2 , —C(O)NHR 2 , C(O)NR 2   2 , —NC(O)R 2 , —S(O) 2 NHR 2 , —S(O) 2 NR 2 , —S(O) 2 R 2 , —P(O) 2 —R 2 , —P(O)—R 2 , —S(O)—R 2 , P(O)—OR 2 , —S(O)—OR 2 , and —N + R 2   3 , wherein R 2  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, or aryl, 
 C—F-connecting group is selected from the group consisting of —SO 2 —O—, —O—SO 2 —O—, —C(O)—O—, —S + (R 3 )—, —C—U—C(V)—O—, —P + (W) 2 —O—, and —P(W)—O—, where U is —C(R 2 ) 2 —, —NR 2 — or —O—; V is ═O or ═NR 2  and W is —OR 2  or —N(R 2 ) 2 ,  
   Functional entity precursor is —C(H)(R 3 )—R 4  or functional entity precursor is heteroaryl or aryl optionally substituted with one or more substituents belonging to the group comprising R 3  and R 4 ,    Wherein R 3  and R 4  independently is H, alkyl, alkenyl, alkynyl, alkadienyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl, optionally substituted with one or more substituents selected from the group consisting of SnR 5 R 6 R 7 , Sn(OR 5 )R 6 R 7 , Sn(OR 5 )(OR 6 )R 7 , BR 5 R 6 , B(OR 5 )R 6 , B(OR 5 )(OR 6 ), halogen, CN, CNO, C(halogen)  3 , OR 5 , OC(═O) R 5 , OC(═O)OR 5 , OC (═O) NR 5 R 6 , SR 5 , S(═O) R 5 , S(═O) 2 R 5 , S(═O) 2 NR 5 R 6 , NO 2 , N 3 , NR 5 R 6 , N + R 5 R 6 R 7 , NR 5 OR 6 , NR 5 N R 6 R 7 , NR 5 C(═O)R 6 , NR 5 C(═O)OR 6 , NR 5 C(═O)NR 6 R 7 , NC, P(═O)(OR 5 )OR 6 , P + R 5 R 6 R 7 , C(═O) R 5 , C(═NR 5 )R 6 , C(═NOR 5 )R 6 , C(═NNR 6 ), C(═O)OR 5 , C(═O)NR 5 R 6 , C(═O)NR 5 OR 6 , C(═O)NR 5 NR 6 R 7 , C(═NR 5 )NR 6 R 7 , C(═NOR 5 )NR 6 R 7  and R 8 , wherein,    R 5 , R 6 , and R 7  independently is H, alkyl, alkenyl, alkynyl, alkadienyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl, optionally substituted with one or more substituents selected from the group consisting of halogen, CN, CNO, C(halogen) 3 , ═O, OR 8 , OC(═O)R 8 , OC(═O)OR 8 , OC(═O)NR 8 R 9 , SR 8 , S(═O)R 8 , S(═O) 2 R 8 , S(═O) 2 NR 8 R 9 , NO 2 , N 3 , NR 8 R 9 , N + R 8 R 9 R 10 , NR 5 OR 6 , NR 5 NR 6 R 7 , NR 8 C(═O)R 9 , NR 8 C(═O)OR 9 , NR 8 C(═O)NR 9 R 10 , NC, P(═O)(OR 8 )OR 9 , P + R 5 R 6 R 7 , C(═O)R 8 , C(═NR 8 )R 9 , C(═NOR 8 )R 9 , C(═NNR 8 R 9 ), C(═O)OR 8 , C(═O)NR 8 R 9 , C(═O)NR 8 OR 9 C(═NR 5 )NR 6 R 7 , C(═NOR 5 )NR 6 R 7  or C(═O)NR 8 NR 9 R 10 , wherein R 5  and R 6  may together form a 3-8 membered heterocyclic ring or R 5  and R 7  may together form a 3-8 membered heterocyclic ring or R 6  and R 7  may together form a 3-8 membered heterocyclic ring, wherein,    R 8 , R 9 , and R 10  independently is H, alkyl, alkenyl, alkynyl, alkadienyl, cycloalkyl, cycloheteroalkyl, aryl or heteroaryl and wherein R 8  and R 9  may together form a 3-8 membered heterocyclic ring or R 8  and R 10  may together form a 3-8 membered heterocyclic ring or R 9  and R 10  may together form a 3-8 membered heterocyclic ring.    
   
   
       2 . A compound according to  claim 1  wherein, 
 Functional entity precursor is —C(H)(R 11 )—R 11 ′ or functional entity precursor is heteroaryl or aryl substituted with 0-3 R 11 , 0-3 R 13  and 0-3 R 15 , wherein    R 11  and R 11 ′ 0  are independently H, or selected from the group consisting of a C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 4 -C 8  alkadienyl, C 3 -C 7  cycloalkyl, C 3 -C 7  cycloheteroalkyl, aryl, and heteroaryl, said group being substituted with 0-3 R 12 , 0-3 R 13  and 0-3 R 15 ,    or R 11  and R 11 ′ are C 1 -C 3  alkylene-NR 12   2 , C 1 -C 3  alkylene-NR 12 C(O)R 16 , C 1 -C 3  alkylene-NR 12 C(O)OR 16 , C 1 -C 2  alkylene-O—NR 12   2 , C 1 -C 2  alkylene-O—N R 12 C(O)R 16 , or C 1 -C 2  alkylene-O—NR 12 C(O)OR 16  substituted with 0-3 R 15 , 
 where R 12  is H or selected independently from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  cycloheteroalkyl, aryl, and heteroaryl, said group being substituted with 0-3 R 13  and 0-3 R 15 ,  
 R 13  is selected independently from the group consisting of —N 3 , —CNO, —C(NOH)NH 2 , —NHOH, —NHNHR 17 , —C(O)R 17 , —SnR 17   3 , —B(OR 17 ) 2 , and —P(O)(OR 17 ) 2  or the group consisting of C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, and C 4 -C 8  alkadienyl, said group being substituted with 0-2 R 14 ,  
 where R 14  is independently selected from the group consisting of —NO 2 , —C(O)OR 17 , —COR 17 , —CN, —OSiR 17   3 , —OR 17  and —NR 17   2 ;  
   R 15  is ═O, —F, —Cl, —Br, —I, —CN, —NO 2 , —OR 17 , —NR 17   2 , —NR 17 —C(O)R 16 , —NR 17 —C(O)OR 17 , —SR 17 , —S(O)R , —S(O) 2 R 17 , —COOR 17 , —C(O)NR 17   2  or —S(O) 2 NR 17   2 ,    R 16  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 7  cycloalkyl, aryl or C 1 -C 6  alkylene-aryl substituted with 0-3 substituents independently selected from —F, —Cl, —NO 2 , —R 2 , —OR , —SiR 2   3 ;    R 17  is selected independently from the group consisting of H, C 1 -C 6  alkyl, C 3 -C 7  cycloalkyl, aryl, C 1 -C 6  alkylene-aryl,                          G is H or C 1 -C 6  alkyl and n is 1,2,3 or 4.    
   
   
       3 . A compound according to  claim 2  wherein, 
 Functional entity precursor is —C(H)(R 11 )—R 11 ′ or functional entity precursor is heteroaryl or aryl substituted with 0-3 R 11 , 0-3 R 13  and 0-3 R 15 , wherein    R 11  and R 11 ′ 0  are independently H, or selected from the group consisting of a C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 4 -C 8  alkadienyl, C 3 -C 7  cycloalkyl, C 3 -C 7  cycloheteroalkyl, aryl, and heteroaryl, said group being substituted with 0-3 R 12 , 0-3 R 13  and 0-3 R 15 ,    or R 11  and R 11 ′ 0  are C 1 -C 3  alkylene-NR 12   2 , C 1 -C 3  alkylene-NR 12 C(O)R 16 , C 1 -C 3  alkylene-NR 12 C(O)OR 16 , C 1 -C 2  alkylene-O—NR 12   2 , C 1 -C 2  alkylene-O—NR 12 C(O)R 16 , C 1 -C 2  alkylene-O—NR 12 C(O)OR 16  substituted with 0-3 R 15 , 
 where R 12  is H or selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  cycloheteroalkyl, aryl, and heteroaryl, said group being substituted with 0-3 R 13  and 0-3 R 15 ,  
 R 13  is selected from the group consisting of —N 3 , —CNO, —C(NOH)NH 2 , —NHOH, —NHNHR 17 , —C(O)R 17 , —SnR 17   3 , —B(OR 17 ) 2 , and —P(O)(OR 17 ) 2  or the group consisting of C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, and C 4 -C 8  alkadienyl, said group being substituted with 0-2 R 14 ,  
 where R 14  is selected from the group consisting of —NO 2 , —C(O)OR 17 , —COR 17 , —CN, —OSiR 17   3 , —OR 17  and —NR 17   2 ;  
   R 15  is ═O, —F, —Cl, —Br, —I, —CN, —NO 2 , —OR 17 , —NR 17   2 , —NR 17 —C(O)R 16 , —NR 17 —C(O)OR 16 , —SR 17 , —S(O)R 17 , —S(O) 2 R 17 , —COOR 17 , —C(O)NR 17   2  or —S(O) 2 NR 17   2 ,    R 16  is H, C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 7  cycloalkyl, aryl or C 1 -C 6  alkylene-aryl substituted with 0-3 substituents independently selected from the group consisting of —F, —Cl, —NO 2 , —R 2 , —OR 2 , and —SiR 2   3 ; wherein R 17  is selected independently from the group consisting of H, C 1 -C 6  alkyl, C 3 -C 7  cycloalkyl, aryl, and C 1 -C 6  alkylene-aryl.    
   
   
       4 . A compound according to  claim 1  wherein, Functional entity precursor is —C(H)(R 11 )—R 11 ′ 0  wherein R 11  and R 11 ′ are C 1 -C 3  alkylene-NR 12   2 , C 1 -C 3  alkylene-NR 12 C(O)R 16 , C 1 -C 3  alkylene-NR 12 C(O)OR 16 , C 1 -C 2  alkylene-O—NR 12   2 , C 1 -C 2  alkylene-O—NR 12 C(O)R 16 , or C 1 -C 2  alkylene-O—NR 12 C(O)OR 16  substituted with 0-3 R 15 .  
   
   
       5 . A compound according to  claim 1  wherein, Functional entity precursor is —C(H)(R 11 )—R 11 ′ wherein R 11  and R 11 ′ are independently H, or selected from the group consisting of a C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 4 -C 8  alkadienyl, C 3 -C 7  cycloalkyl, C 3 -C 7  cycloheteroalkyl, aryl, and heteroaryl, said group being substituted with 0-3 R 12 , 0-3 R 13  and 0-3 R 15 .  
   
   
       6 . A compound according to  claim 2  wherein, Functional entity precursor is —C(H)(R 11 )—R 11 ′ wherein 
 R 11  and R 11 ′ are independently H, or selected from the group consisting of a C 1 -C 6  alkyl, C 3 -C 7  cycloalkyl, C 3 -C 7  cycloheteroalkyl, aryl, and heteroaryl, said group being substituted with 0-3 R 12  and 0-3 R 15 , 
 where R 12  is H or selected from the group consisting of C 1 -C 6  alkyl, C 2 -C 6  alkenyl, C 2 -C 6  alkynyl, C 3 -C 7  cycloalkyl, C 3 -C 7  cycloheteroalkyl, aryl, and heteroaryl,  
   R 15  is ═O, —F, —Cl, —Br, —I, —CN, —NO 2 , —OR 17 , —NR 17   2 , —NR 17 —C(O)R 16 , —NR 17 —C(O)OR 16 , —SR 17 , —S(O)R 17 , —S(O) 2 R 17 , —COOR 17 , —C(O)NR 17   2  or —S(O) 2 NR 17   2 ,    R 17  is selected from the group consisting of H, C 1 -C 6  alkyl, C 3 -C 7  cycloalkyl, and C 1 -C 6  alkylene-aryl.    
   
   
       7 . A compound according to  claim 1  wherein, Functional entity precursor is heteroaryl or aryl substituted with 0-3 R 11 , 0-3 R 13  and 0-3 R 15 .  
   
   
       8 . A compound according to  claim 2  wherein C—F-connecting group is selected from the group consisting of —SO 2 —O—, —O—SO 2 —O—, —C(O)—O—, —S + (R 11 )—, —C—U—C(V)—O—, —P + (W) 2 —O—, and —P(W)—O— where U is —C(R 2 ) 2 —, —NR 2 — or —O—; V is ═O or ═NR 2  and W is —OR 2  or —N(R 2 ) 2 .  
   
   
       9 . A compound according to  claim 2  wherein C—F-connecting group is —S + (R 11 )—.  
   
   
       10 . A compound according to  claim 1  wherein C—F-connecting group is selected from the group consisting of —SO 2 —O—, —O—SO 2 —O—, —C(O)—O—, —S + (R 17 )—, —C—U—C(V)—O—, —P + (W) 2 —O—, and —P(W)—O— where U is —C(R 2 ) 2 —, —NR 2 — or —O—; V is ═O or ═NR 2  and W is —OR 2  or —N(R 2 ) 2 , wherein R 17  is H, C 1 -C 6  alkyl, C 3 -C 7  cycloalkyl, aryl, or C 1 -C 6  alkylene-aryl.  
   
   
       11 . A compound according to wherein C—F-connecting group is chosen from the group consisting of —SO 2 —O—, and —S + (R 17 )—; wherein R 17  is H, C 1 -C 6  alkyl, C 3 -C 7  cycloalkyl, aryl, or C 1 -C 6  alkylene-aryl.  
   
   
       12 . A compound according to  claim 1  wherein, Spacer is a valence bond, C 1 -C 6  alkylene-A—, C 2 -C 6  alkenylene-A—, C 2 -C 6  alkynylene-A—, or  
     
       
         
         
             
             
         
       
     
     said spacer optionally being connected through A to a linker selected from  
     —(CH 2 ) n —B—,  
     
       
         
         
             
             
         
       
     
     and —(CH 2 ) n —S—S—(CH 2 ) m —B—
 where A is a valence bond, —C(O)NR 17 —, —NR 17 —, —O—, —S—, or —C(O)—O—; B is a valence bond, —O—, —S—, —NR 17 — or —C(O)NR 17 — and connects to S—C-connecting group; and n and m independently are integers ranging from 1 to 10; and R 17  is H, C 1 -C 6  alkyl, C 3 -C 7  cycloalkyl, aryl, or C 1 -C 6  alkylene-aryl.  
 
   
   
       13 . A compound according to  claim 1  wherein, Spacer is a valence bond, C 1 -C 6  alkylene-A—, C 2 -C 6  alkenylene-A—, C 2 -C 6  alkynylene-A—, or  
     
       
         
         
             
             
         
       
     
     said spacer optionally being connected through A to a linker selected from —(CH 2 ) n —B—,  
     
       
         
         
             
             
         
       
     
     and 
 where A is a valence bond, —C(O)NR 17 —, —NR 17 —, —S—, or —C(O)—O—; B is —O—, —S—, —NR 17 —, or —C(O)NR 17 — and connects to S—C-connecting group; and n and m independently are integers ranging from 1 to 6; and R 17  is H, C 1 -C 6  alkyl, C 3 -C 7  cycloalkyl, aryl, or C 1 -C 6  alkylene-aryl.  
 
   
   
       14 . A compound according to  claim 1  wherein, S—C-connecting group is a valence bond, —NH—C(═O)—,  
     
       
         
         
             
             
         
       
     
   
   
       15 . A compound according to  claim 2  wherein, the carrier is selected from the group consisting of arylene, heteroarylene and —(CF 2 ) m — substituted with 0-3 R 1  wherein m is an integer between 1 and 10, and C—F-connecting group is —SO 2 —O—, and the functional entity precursor is —C(H)(R 11 )—R 11 ′.  
   
   
       16 . A compound according to  claim 1  wherein, the carrier is —(CF 2 ) m — wherein m is an integer between 1 and 10, the C—F-connecting group is —SO 2 —O—; and the functional entity precursor is aryl or heteroaryl substituted with 0-3 R 11 , 0-3 R 13  and 0-3 R 15 .  
   
   
       17 . A compound according to  claim 1  wherein Complementing element is a nucleic acid.  
   
   
       18 . A compound according to  claim 1  where Complementing element is a sequence of nucleotides selected from the group consisting of DNA, RNA, LNA PNA, and morpholino derivatives.  
   
   
       19 . A library of compounds according to  claim 1 , wherein each different member of the library comprises a complementing element having a unique sequence of nucleotides, which identifies the functional entity.  
   
   
       20 . A method for transferring a functional entity precursor to a recipient reactive group, comprising the steps of 
 providing one or more building blocks according to  claim 1 ,    contacting the one or more building blocks with a corresponding encoding element associated with a recipient reactive group under conditions which allow for a recognition between the one or more complementing elements and the encoding elements, said contacting being performed prior to, simultaneously with, or subsequent to a transfer of the functional entity precursor to the recipient reactive group.    
   
   
       21 . The method according to  claim 20 , wherein the encoding element comprises one or more encoding sequences comprised of 1 to 50 nucleotides and the one or more complementing elements comprises a sequence of nucleotides complementary to one or more of the encoding sequences.  
   
   
       22 . The method of  claim 20 , wherein the recipient reactive group is a nucleophilic S- or N-atom, which may be part of a chemical scaffold, and the activating catalyst is contains palladium.