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

A compound, which is a fluorogenic dimer with two cyanine moieties (D), 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 comprises or consists of a (C2-C10)alkyl group substituted by a functional group consisting of —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 is a saturated or unsaturated hydrocarbon chain attached to an extremity of L in formula (1),
• L is a saturated or unsaturated hydrocarbon group presenting three extremities and comprising from 2 to 40 carbon atoms, where two extremities of said linker L are covalently bonded to both cyanine moieties of formulae (I) or (I′), via both R1, and the third extremity is the remainder of the saturated or unsaturated hydrocarbon group and comprises a reactive group or is attached to a ligand;
• the hydrocarbon chain or group is optionally interrupted by one or several heteroatoms, by one or several connecting groups, or by one or several carbon cycles or heterocycles, the hydrocarbon chain may be further substituted by one or several groups selected from C1-C3 alkyl groups, halogens, —OH, —OMe, and —CF3;
• the reactive group comprises at least one heteroatom and is able to form a covalent bond to another reactive group, forming thereby a connecting group;
• and
• X is an anion bearing a negative charge.