4,4-disubstituted cyclohexyl bridged heptamethine cyanine dyes and uses thereof
AssigneeVisEn Medical, Inc.
InventorNarasimhachari Narayanan
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Abstract
The invention relates to a family of compounds that comprise fluorescent cyanine dyes. The compounds are near infrared absorbing heptamethine cyanine dyes with a 4,4-disubstituted cyclohexyl ring as part of the polymethine chromophore. The compounds are generally hydrophilic and 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.
Claims24
A fluorescent compound represented by Formula I-A:
- or a salt thereof, wherein:
- X1 and X2 are each independently O, S, Se, or C(C1-4 alkyl)2;
- W1 and W2 are a benzo, naphtha, or pyridyl ring;
- R1 and R2 are independently hydrogen or —C1-C10 alkyl optionally substituted with one or two substituents independently selected from the group consisting of halogen, —SO3H, —SO3−, —COOH, —CO2−, and —OH;
- R5, R6, R7 and R8 are each independently H or —C1-C22 alkylene-X3;
- R3, R4, R13 and R14 are each independently H, —C1-C22 alkylene-X3, —SO3H, —SO3, —SO2N(R12)-alkylene-X3, halogen, or —NO2;
- X3 represents independently for each occurrence H, halogen, —CH3, —SO3H, —SO3−, —COOH, —CO2−, —NCS, —NCO, N-hydroxysuccinimidyl ester, N-hydroxysulfosuccinimidyl ester, —OH, —SH, maleimide, phthalimide, —NHCO—(CH2)m-(halogen), —CONHNH2, —CN, —NH2, —NO2, —CON(H)R12, alkynyl, —N3, a polyethyl glycol, optionally substituted aryl, or optionally substituted heterocyclyl;
- R9 and R10 are hydrogen, halogen, or alkyl, or R1 and R9 or R2 and R10 are taken together with their interconnecting atoms to form a 5-, 6- or 7-membered ring;
- R12 represents independently for each occurrence hydrogen or alkyl;
- m represents independently for each occurrence 0, 1, 2, 3, or 4;
- and
- n represents independently for each occurrence 1-10.
A fluorescent compound represented by Formula I-B:
- or a salt thereof, wherein:
- X1 and X2 are each independently O, S, Se, or C(C1-4 alkyl)2;
- W1 and W2 are a benzo, naphtha, or pyridyl ring;
- R1 and R2 are independently hydrogen or —C1-C10 alkyl optionally substituted with one or two substituents independently selected from the group consisting of halogen, —SO3H, —SO3−, —COOH, —CO2−, and —OH;
- R5 and R7 are each independently hydrogen or —C1-C22 alkylene-X3;
- R3, R4, R13 and R14 are each independently hydrogen, —C1-C22 alkylene-X3, —SO3H, —SO3−, —SO2N(R12)-alkylene-X3, halogen, or —NO2;
- X3 represents independently for each occurrence H, halogen, —CH3, —SO3H, —SO3−, —COOH, —CO2−, —NCS, —NCO, N-hydroxysuccinimidyl ester, N-hydroxysulfosuccinimidyl ester, —OH, —SH, maleimide, phthalimide, —NHCO—(CH2)m-(halogen), —CONHNH2, —CN, —NH2, —NO2, —CON(H)R12, alkynyl, —N3, a polyethyl glycol, optionally substituted aryl, or optionally substituted heterocyclyl;
- R9 and R10 are H, halogen, or alkyl, or R1 and R9 or R2 and R10 are taken together with their interconnecting atoms to form a 5-, 6- or 7-membered ring;
- R11 is —COOH, —CN, halogen, —NO2, —C(O)-haloalkyl, haloalkyl, —COOR15, —CON(H)R15, or —CO(CH2)nR15;
- R12 represents independently for each occurrence hydrogen or alkyl;
- R15 is H, —COOH, —SO3H, —NH2, —SH, alkyl, or aryl optionally substituted with X3 and/or a polyethylene glycol;
- m represents independently for each occurrence 0, 1, 2, 3, or 4;
- and
- n represents independently for each occurrence 1-10.
10-28. (canceled)
32-49. (canceled)
53-63. (canceled)
(canceled)
Dependencies are inferred from the claim text.