US 6,617,437 B1 · Pyrimidine derivatives for labeled binding partners

Abstract

Compounds having particular interest as labels and various novel uses in diagnostics and therapeutics are provided which have structure (1) wherein R1 is a binding partner, a linker or H; a and b are 0 or 1, provided that the total of a and b is 0 or 1; A is N or C; X is S, O, —C(O)—, NH or NCH2R6; Y is —C(O)—; Z is taken together with A to form an aryl or heteroaryl ring structure comprising 5 or 6 ring atoms wherein the heteroaryl ring comprises a single O ring heteroatom, a single N ring heteroatom, a single S ring heteroatom, a single O and a single N ring heteroatom separated by a carbon atom, a single S and a single N ring heteroatom separated by a carbon atom, 2 N ring heteroatoms separated by a carbon atom, or 3 N ring heteroatoms at least two of which are separated by a carbon atom, and wherein the aryl or heteroaryl ring carbon atoms are unsubstituted with other than H or at least 1 nonbridging ring carbon atom is substituted with R6 or ═O; R6 is independently H, C1-C6 alkyl, C2-C6 alkeny, C2-C6 alkynyl, NO2, N(R3)2, C≡N or halo, or an R6 is taken together with an adjacent R6 to complete a ring containing 5 or 6 ring atoms;, R3 is a protecting group or H; and tautomers, solvates and salts thereof; and provided that where a is 0, b is 1, and R1 is in which D2 is independently hydroxyl, blocked hydroxyl, mono, di or triphosphate, or an oligodeoxyribonucleotide otherwise containing only the bases A, G, T and C; and D3 is H or OH; then Z is not unsubstituted phenyl. Also provided are novel intermediates and methods for the preparation and use of the structure (1) compounds.

Claims47

Dependent claims

A compound having the structure:

wherein
R1 is a binding partner, a linker or H;
a and b independently are 0 or 1, provided that the total of a and b is 0 or 1;
A is independently N or C;
X is independently S, O, —C(O)—, NH or NCH2R6;
Y is —C(O)—;
Z is taken together with A to form a 5- or 6-membered aryl or heteroaryl ring structure wherein the heteroaryl ring has a single O ring heteroatom, a single N ring heteroatom, a single S ring heteroatom, a single O and a single N ring heteroatom separated by a carbon, a single S and a single N ring heteroatom separated by a carbon, 2N ring heteroatoms separated by a carbon atom, or 3 N ring heteroatoms at least two of which are separated by a carbon atom, and wherein the aryl or heteroaryl ring carbon atoms are unsubstituted or at least 1 nonbridging ring carbon atom is substituted with R6 or ═O;
R6 is independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, NO2, N(R3)2, C≡N or halo, or an R6 is taken together with an adjacent R6 to complete a ring containing 5 or 6 ring atoms;
R3 is a protecting group or H;
and provided that where a is 0, b is 1 and R1 is
in which
D2 is independently hydroxyl, protected hydroxyl, mono, di or triphosphate, or an oligodeoxyribonucleotide otherwise containing only the bases A, G, T and C;
and
D3 is H or OH;
then Z taken together with the A and carbon to which it is bound does not form an unsubstituted phenylene;
and tautomers, solvates and salts thereof.

13 more elements

An oligomer having the structure

wherein
D is OH or blocked OH;
D1 is an oligonucleotide coupling group or OH;
X1 is independently a phosphodiester linkage or a phosphodiester substitute linkage bonded to the 2′ or 3′ position of a furanose ring, and the remaining 2′ or 3′ position is substituted with R21;
R21 is H, OH, F, —O-alkyl (C1-C12), —S-alkyl (C1-C12), OC3H5, or SC3H5;
n is an integer from 0 to 98;
and
B is a purine or pyrimidine base provided that at least one B has the structure
wherein
a and b are 0 or 1 provided that the total of a and b is 0 or 1;
A is N or C;
X is S, O, —C(O)—, NH or NCH2R6;
Y is —C(O)—;
Z together with a and the carbon which Z is bound to form 5- or 6-membered aryl or heteroaryl ring structure wherein the heteroaryl ring has a single O ring heteroatom, a single N ring heteroatom, a single S ring heteroatom, a single O and a single N ring heteroatom separated by a carbon, a single S and a single N ring heteroatom separated by a carbon, 2N ring heteroatoms separated by a carbon atom, or 3 N ring heteroatoms at least two of which are separated by a carbon atom, and wherein the aryl or heteroaryl ring carbon atoms are unsubstituted or at least 1 nonbridging ring carbon atom is substituted with R6 or ═O;
R6 is independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, NO2, N(R3)2, C≡N or halo, or an R6 is taken together with an adjacent R6 to complete a ring containing 5 or 6 ring atoms;
R3 is a protecting group or H;
and provided that where a is 0, b is 1 and R1 is
in which
D2 is independently hydroxyl, protected hydroxyl, mono, di or triphosphate, or an oligodeoxyribonucleotide otherwise containing only the bases A, G, T and C;
and
D3 is H or OH;
then Z is not unsubstituted phenylene;
and tautomers, solvates and salts thereof.

20 more elements

Dependencies are inferred from the claim text.

Pyrimidine derivatives for labeled binding partners

Life of this patent

Pyrimidine derivatives for labeled binding partners

Life of this patent

Abstract

Claims47