Fluorogenic dimer compound, useful as a probe for detection of endogenous receptors

A compound, which is a fluorogenic dimer with two cyanine moieties (D) and a branched linker having three branches (L), which is represented by the following formula (1):

• D-L-D (1);
• where (D) is represented by the following formula (I) or (I′):
• wherein:
• (A) has the following formula:
• (B) has the following formula:
• where the dashed lines are present or not, and, when they are present, they represent single or double carbon bonds;
• R2 is a (C2-C10)alkyl group substituted by a functional group selected from —COOH, —SO3H, and OH;
• a polyethylene glycol represented by the formula
• —(CH2CH2O)n—R′;
• or a polypropylene glycol represented by the formula —(CH2CH2(CH3)O)n—R′, wherein n is an integer from 1 to 40 and R′ is an alkyl group in C1-C12, comprising optionally at least one functional group consisting of —COOH, —SO3H, and OH;
• R3 represents:
• a hydrogen atom,
• a halogen atom,
• a group selected from a (C1-C20)alkyl, a cyclo(C3-C20)alkyl, a (C2-C20)alkenyl, a (C2-C20)alkynyl, a (C1-C5)alkyl-NR″R′″ (R″ and R′″ being independently H or a (C1-C5)alkyl), a heterocyclic group, a cyclo(C3-C20)alkenyl, a heterocyclo(C2-C20)alkenyl, an aryl, a heteroaryl, a hetero(C1-C20)alkyl, a (C1-C20)alkylaryl, and a (C1-C20)alkylheteroaryl, said group being unsubstituted or substituted by one or two substituents selected from a (C1-C5) alkyl, an aryl, an aryl(C1-C5)alkyl, —CONR11R12, or —R13COOH,
• R11 and R12 being independently a hydrogen, a (C1-C20) alkyl, a di(C1-C5)alkylamino(C1-C5)alkyl, optionally substituted by one or more halogen atoms or hydroxy groups, polyethylene glycol represented by the formula —(CH2CH2O)n—R′;
• or a polypropylene glycol represented by the formula —(CH2CH2(CH3)O)n—R′, wherein n is an integer from 1 to 40 and R′ is an alkyl group in C1-C12, or, alternatively, R11 and R12 represents with the nitrogen to which they are attached an heterocycle optionally substituted by a (C1-C4)alkyl,
• R13 being a (C1-C10) alkyl,
• one substituent can optionally be substituted by one or two substituents as defined herein, or
• a group of formula -E-R10, wherein E is selected from —O—, —S—, —NR″—(R″ being H or a (C1-C4)alkyl), and —CH2—;
• and R10 is selected from a (C1-C20)alkyl, a cyclo(C3-C20)alkyl, a (C2-C20)alkenyl, a (C2-C20)alkynyl, a (C1-C5)alkyl-NR″R′″ (R″ and R′″ being independently H or a (C1-C5)alkyl), a heterocyclic group, a cyclo(C3-C20)alkenyl, a heterocyclo(C2-C20)alkenyl, an aryl, a heteroaryl, a hetero(C1-C20)alkyl, a (C1-C20)alkylaryl, a (C1-C20)alkylheteroaryl, R10 being unsubstituted or substituted by one to three substituents selected from a (C1-C5) alkyl, an aryl, an aryl(C1-C5)alkyl, —CONR11R12, or —R13COOH;
• R11 and R12 being independently a hydrogen, a (C1-C20) alkyl, a di(C1-C5)alkylamino(C1-C5)alkyl, optionally substituted by one or more halogen atoms or hydroxy groups, or, alternatively, or alternatively R11 and R12 represents with the nitrogen to which they are attached an heterocycle optionally substituted by a (C1-C4)alkyl,
• R13 being a (C1-C10) alkyl,
• one substituent can optionally be substituted by one or two substituents as defined herein,
• R4, if present, represents:
• a hydrogen atom,
• a group selected from a (C1-C20)alkyl, a cyclo(C3-C20)alkyl, a (C2-C20)alkenyl, a (C2-C20)alkynyl, a heterocyclic group, a cyclo(C3-C20)alkenyl, a heterocyclo(C2-C20)alkenyl, an aryl, a heteroaryl, a hetero(C1-C20)alkyl, a (C1-C20)alkylaryl, or a (C1-C20)alkylheteroaryl, said group being unsubstituted or substituted by one or two substituents selected from a (C1-C5) alkyl, an aryl, or —R13COOH,
• R13 being a (C1-C20) alkyl, or
• a group of formula -E-R10, wherein E is selected from —O—, —S—, —NH—, or —CH2—;
• R10 is selected from a (C1-C20)alkyl, a cyclo(C3-C20)alkyl, a (C2-C20)alkenyl, a (C2-C20)alkynyl, a heterocyclic group, a cyclo(C3-C20)alkenyl, a heterocyclo(C2-C20)alkenyl, an aryl, a heteroaryl, a hetero(C1-C20)alkyl, a (C1-C20)alkylaryl, a (C1-C20)alkylheteroaryl, R10 being unsubstituted or substituted by one to three substituents selected from a (C1-C5) alkyl, an aryl, or —R13COOH, R13 being a (C1-C10) alkyl;
• R1, on each cyanine moiety, is a saturated or unsaturated hydrocarbon chain covalently bonded to a branch of in formula (1),
• L is a branched saturated or unsaturated hydrocarbon group of 2 to 40 carbon atoms having three branches, two of said branches being covalently bonded to cyanine moieties of formulae (I) or (I′) via R1 on each cyanine moiety and the third branch is the remainder of the branched saturated or unsaturated hydrocarbon group and comprises a group able to react through a click reaction or a bioconjugation reaction or is attached to a ligand;
• wherein R1 and L, independently, is optionally interrupted by one or several heteroatoms, by one or several connecting groups, or by one or several carbon cycles or heterocycles, R1 and L, independently, may be further substituted by one or several groups selected from C1-C3 alkyl groups, halogens, —OH, —OMe, and —CF3;
• and
• X is an anion bearing a negative charge.