Near-infrared fluorescent heptamethine dye conjugates with favorable bleaching properties

A compound according to formula (II)

• wherein
• R1, R2, R6, R7, R14, R15, R16, R17, and R18 are independently selected from the group consisting of H and (C1-C6)alkyl;
• R3 is —SO3X3, or COOH;
• Z is a protein, mono- or polyvalent saccharide, peptide, small molecule, antibody, oligonucleotide, nanobody, or polymer;
• R5 is —SO3X4;
• R8, R9, R10, R11, R12 and R13 are independently selected from the group consisting of H, CN, —COO(C1-C6)alkyl, —CONH(C1-C6)alkyl, Cl, Br, I, F, —CF3, —O(C1-C6), —NR14R15, —NHC(O)(C1-C6)alkyl, —NHC(O)NH(C1-C6)alkyl), —SO3H, —SO2NH2, -(C1-C6)alkyl;
• R19, R20 are independently selected from the group consisting of H, -(C1-C6)alkyl, —O(C1-C6)alkyl, Cl, F, Br, CN;
• C(O)NH2;
• R21 is H, -(C1-C10)alkyl;
• X1, X2, X3, and X4 are independently selected from a cation, a proton or absent;
• Q is —(CH2)n2—,
• wherein optionally one or more of each H in —(CH2)n2— may be replaced by -(C1-C10)alkyl;
• n2 is an integer between 1 to 10;
• preferably 1 to 1;
• Y is —(CH2)n3—,
• wherein optionally one or more of each H in —(CH2)n3— may be replaced by -(C1-C10)alkyl;
• n3 is an integer between 1 to 10;
• L is selected from the group:
• —(CH2)n1—, -(C1-C6)cycloalkylene-, -(C1-C6)heterocycloalkylene-, —O—, —NR16−, —NH—, —NHC(O)—, —C(O)NR17—, —CH(OH)—, —CH(OR18)—, and combinations thereof;
• n1 is an integer between 1 to 30;
• L1 is selected from the group consisting of
• —CO—;
• L2 is a selected from the group:
• —(CH2)n1—, -(C1-C6)cycloalkylene-, -(C1-C6)heterocycloalkylene-, —O—, —NR16—, —NH—, —NHC(O)—, —C(O)NR17—, —CH(OH)—, —CH(OR18)—, and combinations thereof.

A method of diagnosing an indication in a subject in need thereof, comprising the step of administering a compound according to formula (II)

• wherein
• R1, R2, R6, R7, R14, R15, R16, R17, and R8 are independently selected from the group consisting of H and (C1-C6)alkyl;
• R3 is —SO3X3, or COOH;
• Z is a protein, mono- or polyvalent saccharide, peptide, small molecule, antibody, oligonucleotide, nanobody, or polymer;
• R5 is —SO3X4;
• R8, R9, R10, R11, R12 and R13 are independently selected from the group consisting of H, CN, —COO(C1-C6)alkyl, —CONH(C1-C6)alkyl, Cl, Br, I, F, —CF3, —O(C1-C6), —NR14R15, —NHC(O)(C1-C6)alkyl, —NHC(O)NH(C1-C6)alkyl), —SO3H, —SO2NH2, -(C1-C6)alkyl;
• R19, R20 are independently selected from the group consisting of H, -(C1-C6)alkyl, —O(C1-C6)alkyl, Cl, F, Br, CN;
• C(O)NH2;
• R21 is H, -(C1-C10)alkyl;
• X1, X2, X3, and X4 are independently selected from a cation, a proton or absent;
• Q is —(CH2)n2—,
• wherein optionally one or more of each H in —(CH2)n2— may be replaced by -(C1-C10)alkyl;
• n2 is an integer between 1 to 10;
• Y is —(CH2)n3—,
• wherein optionally one or more of each H in —(CH2)n3— may be replaced by -(C1-C10)alkyl;
• n3 is an integer between 1 to 10;
• L is selected from the group:
• —(CH2)n1—, -(C1-C6)cycloalkylene-, -(C1-C6)heterocycloalkylene-, —O—, —NR16—, —NH—, —NHC(O)—, —C(O)NR17—, —CH(OH)—, —CH(OR18)—, and combinations thereof;
• n is an integer between 1 to 30;
• L1 is selected from the group consisting of
• —CO—;
• L2 is selected from the group:
• —(CH2)n1—, -(C1-C6)cycloalkylene-, -(C1-C6)heterocycloalkylene-, —O—, —NR16—, —NH—, —NHC(O)—, —C(O)NR17—, —CH(OH)—, —CH(OR18)—, and combinations thereof;
• and
• irradiating the compound with light having a wavelength between 400 nm and 1200 nm.