US2006035262A1PendingUtilityA1

Dark quenchers for donor-acceptor energy transfer

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Assignee: BIOSEARCH TECHNOLOGIES INCPriority: May 9, 2000Filed: Sep 13, 2005Published: Feb 16, 2006
Est. expiryMay 9, 2020(expired)· nominal 20-yr term from priority
C07C 245/08G01N 33/582C12Q 1/6818C09B 56/00C07D 241/46G01N 33/542C40B 40/00C09B 31/043C07F 9/2408C07F 9/091C07B 2200/11C09B 56/12C07H 21/00
59
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Claims

Abstract

The present invention provides a family of dark quenchers, termed Black Hole Quenchers (“BHQs”), that are efficient quenchers of excited state energy but which are themselves substantially non-fluorescent. Also provided are methods of using the BHQs, probes incorporating the BHQs and methods of using the probes.

Claims

exact text as granted — not AI-modified
1 - 87 . (canceled)  
     
     
         88 . A compound having the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 Ar 1  and Ar 2  are each independently a substituted or unsubstituted aryl group, where at least one of Ar 1  and Ar 2  is a substituted aryl;  
 X 1  is selected from the group consisting of OH, O-dimethoxytrityl, O-methoxytrityl, O-trityl  
 and an oxygen atom having an acid labile blocking group;  
 X 2  is a phosphoramidite; and  
 W is a linking group having from 3 to 100 backbone atoms selected from C, N, O, S, Si and P, said linking group being cyclic, acyclic, aromatic or a combination thereof.  
 
     
     
         89 . A compound having the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 Ar 1  and Ar 2  are each independently a substituted or unsubstituted aryl group, where at least one of Ar 1  and Ar 2  is a substituted aryl;  
 X 1  is selected from the group consisting of H, (C 1 -C 1-C12 )alkyl, aryl, heteroaryl, and protected or unprotected functional group;  
 X 2  is selected from the group consisting of a phosphorous coupling moiety, a pentafluorophenoxy moiety and a succinimidyl moiety; and  
 W is a linking group having from 3 to 100 backbone atoms selected from C, N, O, S, Si and P, said linking group being cyclic, acyclic, aromatic or a combination thereof.  
 
     
     
         90 . A compound having the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 Ar 1  and Ar 2  are each independently a substituted or unsubstituted aryl group, where at least one of Ar 1  and Ar 2  is a substituted aryl;  
 X 1 , is selected from the group consisting of H, (C 1 -C 12 )alkyl, aryl, heteroaryl and protected or unprotected functional group;  
 X 2  is a phosphoramidite; and  
 W is a linking group having from 3 to 100 backbone atoms selected from C, N, O, S, Si and P, said linking group being cyclic, acyclic, aromatic or a combination thereof.  
 
     
     
         91 . A compound having the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 Ar 1  and Ar 2  are each independently a substituted or unsubstituted aryl group;  
 X 1  is selected from the group consisting of H, (C 1 -C 12 )alkyl, aryl, heteroaryl, and protected or unprotected finctional group;  
 X 2  is a moiety reactive towards nucleophiles;  
 W is a linking group having from 3 to 100 backbone atoms selected from C, N, O, S, Si and P, said linking group being cyclic, acyclic, aromatic or a combination thereof; and  
 wherein one of Ar 1  and A 2  is directly or indirectly substituted with a substituted aryl group (A 3 ), where Ar 3  extends the resonance ability of the Ar 1 —N═N-A 2  aromatic system and thereby increases the wavelength absorbance maximum of the compound.  
 
     
     
         92 . A compound of  claim 91  wherein Ar 1  is directly substituted with Ar 3 .  
     
     
         93 . A compound of  claim 91  wherein Ar 1  is indirectly substituted with Ar 3 .  
     
     
         94 . A compound of  claim 91  wherein A 2  is directly substituted with Ar 3 .  
     
     
         95 . A compound of  claim 91  wherein Ar 2  is indirectly substituted with Ar 3 .  
     
     
         96 . A compound having the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 Ar 1  and A 2  are each independently a substituted or unsubstituted aryl group;  
 X 1 , is selected from the, group consisting of H, (C 1 -C 12 )alkyl, aryl, heteroaryl, and protected or unprotected functional group;  
 X 2  is a phosphoramidite;  
 W is a linking group having from 3 to 100 backbone atoms selected from C, N, O, S, Si and P, said linking group being cyclic, acyclic, aromatic or a combination thereof; and  
 wherein Ar 1  or Ar 2  is indirectly substituted with an aryl group through a group selected from —(C═C) n — and —(CR′CR′) n — where n is 0 to 5 and R′ is independently selected from hydrogen, (C 1 -C 8 )alkyl and heteroalkyl, unsubstituted aryl and heteroaryl, (unsubstituted aryl)-(C 1 -C 4 )alkyl, and (u nsubstituted aryl)oxy-(C 1 -C 4 )alkyl.  
 
     
     
         97 . A compound having the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 Ar 1  and Ar 2  are each independently a substituted or unsubstituted aryl group;  
 X 1  is selected from the group consisting of H, (C 1 -C 12 )alkyl, aryl, heteroaryl, and protected or unprotected functional group;  
 X 2  is a phosphoramidite;  
 W is a linking group having from 3 to 100 backbone atoms selected from C, N, O, S, Si and P, said linking group being cyclic, acyclic, aromatic or a combination thereof; and  
 Ar 1  or Ar 2  is indirectly substituted with an aryl group (Ar 3 ) through a double bond selected from carbon-carbon and nitrogen-nitrogen double bonds.  
 
     
     
         98 . A compound having the formula:  
       
         
           
           
               
               
           
         
       
       wherein 
 Ar 1  and A 2  are each independently a substituted or unsubstituted aryl group;  
 X 1  is selected from the group consisting of H, (C 1 -C 12 )alkyl, aryl, heteroaryl, and protected or unprotected functional group;  
 X 2  is a phosphoramidite;  
 W is a linking group having from 3 to 100 backbone atoms selected from C, N, O, S, Si and P, said linking group being cyclic, acyclic, aromatic or a combination thereof;  
 wherein one of Ar 1  and Ar 2  is directly or indirectly substituted with a substituted aryl group (Ar 3 ), where Ar 3  extends the resonance ability of the Ar 1 —N═N—Ar 2  aromatic system and thereby increases the wavelength absorbance maximum of the compound; and  
 at least one of Ar 1 , A 2 and Ar 3 is substituted with -halogen, —OR′, —OC(O)R′, —NR′R″, —SR′, —R′, —CN, —NO 2 , —CO 2 R′, —CONR′R″, —C(O)R′, —OC(O)NR′R″, —NR″C(O)R′, —NRC″C(O) 2 R′, —NR′—C(O)NR″R′″, —NH—C(NH 2 )NH, —NR′C(NH 2 )NH, —NH—C(NH 2 )═NR′, —S(O)R′, —S(O) 2 R′, —S(O) 2 NR′R″, —N3, —CH(Ph) 2 , perfluoro(C 1 -C 4 )alkoxy, and perfluoro(C 1 -C 4 )alkyl, in a number ranging from zero to the total number of open valences on the aromatic ring system; and where R′, R″ and R′″ are independently selected from hydrogen, (C 1 -C 8 )alkyl and heteroalkyl, unsubstituted aryl and heteroaryl, (unsubstituted aryl)-(C 1 -C 4 )alkyl, and (unsubstituted aryl)oxy-(C 1 -C 4 )alkyl.  
 
     
     
         99 . A compound of  claim 88  wherein W is acylic.  
     
     
         100 . A compound of  claim 88  wherein W comprises a cyclic group.  
     
     
         101 . A compound of  claim 89  wherein W is a cyclic.  
     
     
         102 . A compound of  claim 89  wherein W comprises a cyclic group.  
     
     
         103 . A compound of  claim 90  wherein W is acyclic.  
     
     
         104 . A compound of  claim 90  wherein W comprises a cyclic group.  
     
     
         105 . A compound of  claim 91  wherein W is acyclic.  
     
     
         106 . A compound of  claim 91  wherein W comprises a cyclic group.  
     
     
         107 . A compound of  claim 92  wherein W is acyclic.  
     
     
         108 . A compound of  claim 92  wherein W comprises a cyclic group.  
     
     
         109 . A compound of  claim 93  wherein W is a cyclic.  
     
     
         110 . A compound of  claim 93  wherein W comprises a cyclic group.  
     
     
         111 . A compound of  claim 94  wherein W is acyclic.  
     
     
         112 . A compound of  claim 94  wherein W comprises a cyclic group.  
     
     
         113 . A compound of  claim 95  wherein W is acyclic.  
     
     
         114 . A compound of  claim 95  wherein W comprises a cyclic group.  
     
     
         115 . A compound of  claim 96  wherein W is acyclic.  
     
     
         116 . A compound of  claim 96  wherein W comprises a cyclic group.  
     
     
         117 . A compound of  claim 97  wherein W is cyclic.  
     
     
         118 . A compound of  claim 97  wherein W comprises a cyclic group.  
     
     
         119 . A compound of  claim 98  wherein W is acyclic.  
     
     
         120 . A compound of  claim 98  wherein W comprises a cyclic group.  
     
     
         121 . A compound of claims  89 ,  91 - 95  or  105 - 114  wherein X 2  is a phosphoramidite.

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