Polycyclo dyes and use thereof

摘要

The invention relates to a family of fluorescent compounds that comprise a bridged polycyclo moiety. The compounds can be chemically linked to biomolecules, such as proteins, nucleic acids, and therapeutic small molecules. The compounds can be used for imaging in a variety of medical, biological and diagnostic applications, and are particularly useful for the in vivo imaging of regions of interest within a mammal.

主权项

1. A compound represented by:or a salt thereof, wherein:
X1 and X2 each independently are selected from the group consisting of C(CH2K1)(CH2K2) and O, wherein:
K1 and K2 each independently are selected from the group consisting of H and C1-C20 alkyl; wherein K1 and K2 together can optionally form part of a cyclic ring; R1 and R2 each independently are selected from the group consisting of H, C1-20 alkyl, alkylaryl, and —R9T1, wherein
R9 is independently selected from the group consisting of C1-C20 alkyl, aryl, alkylaryl, and —(CH2—O—CH2)yCH2, wherein y is an integer selected from 1 to 100, andT1 is a linker moiety capable of forming a covalent bond with a biomolecule; X3 is selected from the group consisting of: O—(CH2)j-T1, S—(CH2)j-T1, O-Ph-(CH2)j-T1, S-Ph-(CH2)j-T1, wherein
j is an integer from 0 to 6;Ph is phenyl X4 and X5 each independently are selected from the group consisting of (CK1K2)i; O, and S, wherein
i is an integer selected from 1 to 7, and W1 and W2 each represent nonmetal atoms as part of an aryl moiety; n1 and n2 each independently are selected from 0 to 4; R3, R4, R5 and R6 each independently are selected from the group consisting of H, halogen, carboxylate, carboxylic acid, carboxylic ester, amine, amide, sulfonamide, hydroxyl, O-alkyl, S-alkyl, alkyl, sulfonic acid, sulfonate, a phosphoryl, SO2NR7-Q-CHR8—[(CH2)m—Y—(CH2)p—(O)k]h(CH2)d T1, and —R9T1, wherein
R7 independently is selected from the group consisting of C1-C20 alkyl, aryl, alkylaryl,R8 independently is selected from the group consisting of H, C1-C20 alkyl, aryl, alkylaryl and arylalkyl;R7 and R8, when taken in combination, optionally form a 4-, 5-, 6- or 7-member, optionally substituted, saturated or unsaturated ring,Q independently is selected from the group consisting of a bond, carbonyl, C1-C6 alkyl, and C1-C6 cycloalkyl,Y independently is selected from the group consisting of a bond, —SO2NR1—, —O—, —COO—, and —CONR′—,h is an integer selected from 0 to 70,k is 0 or 1,d is an integer from 0 to 12,m is an integer from 0 to 12, andp is an integer from 0 to 12.