Hydrophilic cyanine dyes
AssigneeMallinckrodt Inc.
InventorsSamuel Achilefu, Raghavan Rajagopalan, Richard B. Dorshow, Joseph E. Bugaj
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Abstract
The sensitivity and specificity of the optical modality can be enhanced by the use of highly absorbing dyes as contrast agents. Novel cyanine dyes that absorb and emit light in the near infrared region of electromagnetic spectrum are disclosed. These dyes are useful for imaging, diagnosis and therapy of various diseased states. Particularly, the molecules of the invention are useful for optical diagnostic imaging and therapy, in endoscopic applications for the detection of tumors and other abnormalities, for localized therapy, for photoacoustic tumor imaging, detection and therapy, and for sonofluorescence tumor imaging, detection and therapy.
Claims16
A composition comprising cyanine dyes of formula
- wherein a3 and b3 are independently 0 to 5;
- W3 and X3 are independently selected from the group consisting of C((CH2)zzOH)2, C((CH2)zzCO2H)2, and C((CH2)zzNRppRpz)2;
- and zz is from 1 to 5;
- Rpp and Rpz are independently selected from the group consisting of —(CH2)c—CO2H, —CH2—(CH2—O—CH2)d—CH2—CO2H, —(CH2)g—N(R14)—(CH2)h—CO2H, and —(CH2)i—N(R15)—CH2—(CH2—O—CH2)j—CH2—CO2H;
- Y3 and Z3 are independently selected from the group consisting of —(CH2)c—CO2H, —CH2—(CH2—O—CH2)d—CH2—CO2H, —(CH2)e—NH2, —CH2—(CH2—O—CH2)f—CH2—NH2, —(CH2)g—N(R14)—(CH2)h—CO2H, and —(CH2)i—N(R15)—CH2—(CH2—O—CH2)j—CH2—CO2H;
- A1 is a single or a double bond;
- if A1 is a single bond, then B1 and C1 are independently selected from the group consisting of —O—, —S—, —Se—, —P— and —NR38;
- and D1 is selected from —CR39R40 and —C═O;
- if A1 is a double bond, then B1 is selected from the group consisting of —O—, —S—, —Se—, —P— and —NR38, C1 is selected from nitrogen and —CR41 and D1 is —CR42;
- R29 to R37 are independently selected from the group consisting of hydrogen, C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, nitro, halogen, and —NR43R44;
- R14, R15, and R38 to R42 are independently selected from the group consisting of -hydrogen, C1-C10 alkyl, C1-C10 alkoxyl, —CH2(CH2—O—CH2)c—CH2—OH, —(CH2)d—CO2H, —CH2—(CH2—O—CH2)e—CH2—CO2H, —(CH2)f—NH2, and —CH2—(CH2—O—CH2)g—CH2—NH2;
- c, e, g, h, and i are independently from 1 to 10;
- d, f and j are independently from 1 to 100;
- R43 and R44 are independently selected from the group consisting of hydrogen, and C1-C10 alkyl, and a pharmaceutically acceptable carrier or excipient.
A method for performing a diagnostic or therapeutic procedure which comprises administering to an individual an effective amount of the composition of cyanine dyes of the formula
- wherein a3 and b3 are independently from 0 to 5;
- W3 and X3 are independently selected from the group consisting of C((CH2)zzOH)2, C((CH2)zzCO2H)2, and C((CH2)zzNRppRpz)2;
- and zz is from 1 to 5;
- Rpp and Rpz are independently selected from the group consisting of —(CH2)c—CO2H, —CH2—(CH2—O—CH2)d—CH2—CO2H, —(CH2)g—N(R14)—(CH2)h—CO2H, and —(CH2)i—N(R15)—CH2—(CH2—O—CH2)j—CH2—CO2H;
- Y3 and Z3 are independently selected from the group consisting of —(CH2)c—CO2H, —CH2—(CH2—O—CH2)d—CH2—CO2H, —(CH2)e—NH2, —CH2—(CH2—O—CH2)f—CH2—NH2, —(CH2)g—N(R14)—(CH2)h—CO2H, and —(CH2)i—N(R15)—CH2—(CH2—O—CH2)j—CH2—CO2H;
- A1 is a single or a double bond;
- if A1 is a single bond, then B1 and C1 are independently selected from the group consisting of —O—, —S—, —Se—, —P— and —NR38, and D1 is selected from —CR39R40 and —C═O;
- if A1 is a double bond, then B1 is selected from the group consisting of —O—, —S—, —Se—, —P— and —NR38, C1 is selected from nitrogen and —CR41 and D1 is —CR42;
- R29 to R37 are independently selected from the group consisting of hydrogen, C1-C10 alkyl, hydroxyl, C1-C10 alkoxyl, cyano, nitro, halogen, and —NR43R44;
- R14, R15, and R38 to R42 are independently selected from the group consisting of -hydrogen, C1-C10 alkyl, C1-C10 alkoxyl, —CH2(CH2—O—CH2)c—CH2—OH, —(CH2)d—CO2H, —CH2—(CH2—O—CH2)e—CH2—CO2H, —(CH2)f—NH2, and —CH2—(CH2—O—CH2)g—CH2—NH2;
- c, e, g, h, and i are independently from 1 to 10;
- d, f and j are independently from 1 to 100;
- R43 and R44 are independently selected from the group consisting of hydrogen and C1-C10 alkyl.
Dependencies are inferred from the claim text.