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Triphosphate oligonucleotide modification reagents and uses thereof

  • US 7,999,098 B2
  • Filed: 12/11/2006
  • Issued: 08/16/2011
  • Est. Priority Date: 08/01/2000
  • Status: Active Grant
First Claim
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1. A compound that has formula (I):


  • P1

    S1

    B1-M-Xor a derivative thereof, wherein;

    P1 is a triphosphate group;

    S1 is a ribose or a dideoxyribose;

    B1 is a nucleobase;

    X is a protected or unprotected hydrazino group, a protected or unprotected oxyamino group, or a carbonyl derivative; and

    M is a divalent group comprising any combination of any of the following groups, which are combined in any order;

    arylene, heteroarylene, cycloalkylene, C(R1)2, —

    C(R1)═

    C(R1)—

    , >

    C═

    C(R2)(R3), >

    C(R2)(R3), —

    C≡

    C—

    , O, S(A)a, P(D)b(R1), P(D)b(ER1), N(R1), >

    N+(R2)(R3) and C(E);

    where a is 0, 1 or 2;

    b is 0, 1, 2 or 3;

    A is O or NR1;

    D is S or O; and

    E is S, O or NR1;

    wherein;

    each R1 is a monovalent group independently selected from hydrogen and M1-R4;

    each M1 is a divalent group each independently comprising any combination of the following groups, which groups are combined in any order;

    a direct link, arylene, heteroarylene, cycloalkylene, C(R5)2, —

    C(R5)═

    C(R5)—

    , >

    C═

    C(R2)(R3), >

    C(R2)(R3), —

    C≡

    C—

    , O, S(A)a, P(D)b(R5), P(D)b(ER5), N(R5), N(COR5), >

    N+(R2)(R3) and C(E);

    where a is 0, 1 or 2;

    b is 0, 1, 2 or 3;

    A is O or NR5;

    D is S or O; and

    E is S, O or NR5;

    R4 and R5 are each independently selected from the group consisting of hydrogen, halo, pseudohalo, cyano, azido, nitro, SiR6R7R8, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR9R10;

    R9 and R10 are each independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, aralkyl, heteroaryl, heteroaralkyl and heterocyclyl;

    R2 and R3 are selected from (i) or (ii) as follows;

    (i) R2 and R3 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl and heteroaryl;

    or(ii) R2 and R3 together form alkylene, alkenylene or cycloalkylene;

    R6, R7 and R8 are each independently a monovalent group selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy and NR9R10; and

    each R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 is unsubstituted or substituted with one or more substituents each independently selected from Z, wherein Z is selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl, hydroxy, S(O)hR20, NR20R21, COOR20, COR20, CONR20R21, OC(O)NR20R21, N(R20)C(O)R21, alkoxy, aryloxy, heteroaryl, heterocyclyl, heteroaryloxy, heterocyclyloxy, aralkyl, aralkenyl, aralkynyl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, aralkoxy, heteroaralkoxy, alkoxycarbonyl, carbamoyl, thiocarbamoyl, alkoxycarbonyl, carboxyaryl, halo, pseudohalo, haloalkyl and carboxamido;

    h is 0, 1 or 2; and

    R20and R21 are each independently selected from the group consisting of hydrogen, halo, pseudohalo, cyano, azido, nitro, trialkylsilyl, dialkylarylsilyl, alkyldiarylsilyl, triarylsilyl, alkyl, alkenyl, alkynyl, haloalkyl, haloalkoxy, aryl, aralkyl, aralkenyl, aralkynyl, heteroaryl, heteroaralkyl, heteroaralkenyl, heteroaralkynyl, heterocyclyl, heterocyclylalkyl, heterocyclylalkenyl, heterocyclylalkynyl, hydroxy, alkoxy, aryloxy, aralkoxy, heteroaralkoxy, amino, amido, alkylamino, dialkylamino, alkylarylamino, diarylamino and arylamino.

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