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US 12,359,069 B2Granted
Azacyanine dyes and use thereof
OwnerRiccardo Sinisi, Alma Rosa Morales Morales +3inventors
InventorsRiccardo Sinisi, Alma Rosa Morales Morales, Elena A. Goun, Rajendra Singh, Pavlo Khodakivskyi
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Abstract
The application provides fluorescent dyes, which are cyanine dyes that incorporate additional aza moieties in the indolenium heterocycles and/or in the methine chains connecting them. Symmetrical and unsymmetrical chemically reactive azacyanine dyes are described for conjugation, as well as their bioconjugates for in-vitro and in-vivo assays and fluorescence imaging.
Claims12
A fluorescent dye of formula A:
- or a salt thereof, wherein
- Z is selected from the group consisting of NR17 and +NR17R18;
- Q is selected from the group consisting of Cl, Br, I, and R19U, —OR19U, —SR19U, —NHR19U, and NR19R20U, wherein R19 and R20 are independently selected from the group consisting of:
- linear and branched, non-cyclic and cyclic, substituted and unsubstituted C1-20 alkyl, wherein the alkyl group can be single or multiple substituted by a homocyclic or heterocyclic C5-, C6- or C7-aromatic ring which can be substituted by a linear or branched C1-C6 alkyl group and —(CH2—O—CH2)xCH2—;
- and U is selected from the group consisting of:
- —(CH2)mSO3−, —(CH2)mC(O)O−, —(CH2)mP(O)O22−, —(CH2)mNH2, —(CH2)mNHR32, and —(CH2)mNR32R33;
- and wherein in case of —(CH2)mNH2, —(CH2)mNHR32, and —(CH2)mNR32R33 the N atom may be bound to a further substituent R34 to form a quaternary N atom, and wherein R34 is in all the above cases independently selected from H and an alkyl group having from 1-12 C atoms,
- R1 and R2 are selected from the group consisting of absent, H, and linear and branched, non-cyclic and cyclic, substituted and unsubstituted C1-20 alkyl, wherein the alkyl group can be single or multiple substituted by homocyclic and heterocyclic 5-, 6- and 7-membered aromatic rings which can be substituted by a linear or branched C1-C6 alkyl group;
- R17 and R18 are absent or are independently selected from the group consisting of H and linear and branched, non-cyclic or cyclic, substituted and unsubstituted C1-20 alkyl, wherein the alkyl group can be single or multiple substituted by homocyclic and heterocyclic 5-, 6-, and 7-membered aromatic rings which can be substituted by a linear or branched C1-C6 alkyl group;
- A6 and A10 are C, N, or +N;
- A7, A8, A9, and A11, A12, A13 are C, and form a 6-membered aromatic ring which together with the pyrrolin derived ring to which they are attached form an indol or an azaindol system, and, optionally, to which indol or azaindol system a further 6-membered ring is annulated which is formed by R5 and R6, and R9 and R10;
- R4 and R8 are independently H;
- R3 and R7, and also R5, R6, R9, and R10 when they are not annulated with the further 6-membered ring, are independently selected from the group consisting of absent, H, Cl, Br, I, R25H, and OR25H;
- R25 is selected from the group:
- linear and branched, non-cyclic and cyclic, substituted and unsubstituted C1-20 alkyl, wherein the alkyl group can be single or multiple substituted by a homocyclic or heterocyclic 5-, 6-, or 7-membered aromatic group which can be substituted by a linear or branched C1-C6 alkyl group;
- m is an integer from 0 to 6;
- x is an integer from 1 to 50;
- R32 and R33 are independently of each other an alkyl group having from 1-12 C atoms;
- X and Y are CR29R30, where R29 and R30 are each independently selected from H, and unsubstituted and substituted linear or branched, cyclic or non-cyclic C1-C6 alkyl;
- and
- E and E′ are independently selected from H, and unsubstituted and substituted linear or branched, cyclic or non-cyclic C1-C6 alkyl.
18 more elements
Dependencies are inferred from the claim text.