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US 7,252,815 B2Granted
Pathological tissue detection and treatment employing targeted benzoindole optical agents
AssigneeMallinckrodt Inc.
InventorsSamuel Achilefu, Richard B. Dorshow, Raghavan Rajagopalan, Joseph E. Bugaj
Life of this patent
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Abstract
Novel tumor specific phototherapeutic and photodiagnostic agents are disclosed. The compounds consist of a carbocyanine dye for visualization, photosensitizer for photodynamic treatment, and tumor receptor-avid peptide for site-specific delivery of the probe and phototoxic agent to diseased tissues. A combination of these elements takes full advantage of the unique and efficient properties of each component for an effective patient care management.
Claims22
A compound having the carbocyanine dye bioconjugate of formula 2
- wherein W1 and W2 are S;
- Y1, Y2, Z1, and Z2 are independently selected from the group consisting of hydrogen, tumor-specific agent, phototherapy agent, —CONH-Bm, —NHCO-Bm, —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—N(R12)—(CH2)b—CONH-Bm, (CH2)a—N(R12)—(CH2)c—NHCO-Bm, —(CH2)a—N(R12)—CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—N(R12)—CH2—(CH2OCH2)b—CH2—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—N(R12)—(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—N(R12)—(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—N(R12)—CH2—(CH2OCH2)d—CONH-Bm, —CH2—(CH2OCH2)b—CH2—N(R12)—CH2—(CH2OCH2)d—NHCO-Bm, —CONH-Dm, —NHCO-Dm, —(CH2)a—CONH-Dm, —CH2—(CH2OCH2)b—CH2—CONH-Dm, —(CH2)a—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—NHCO-Dm, —(CH2)a—N(R12)—(CH2)b—CONH-Dm, —(CH2)a—N(R12)—(CH2)c—NHCO-Dm, —(CH2)a—N(R12)—CH2—(CH2OCH2)b—CH2—CONH-Dm, —(CH2)a—N(R12)—CH2—(CH2OCH2)b—CH2—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—N(R12)—(CH2)a—CONH-Dm, —CH2—(CH2OCH2)b—CH2—N(R12)—(CH2)a—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—N(R12)—CH2—(CH2OCH2)d—CONH-Dm, —CH2—(CH2OCH2)b—CH2—N(R12)—CH2—(CH2OCH2)d—NHCO-Dm, —(CH2)a—N R12R13, and —CH2(CH2OCH2)b—CH2N R12R13;
- K1 and K2 are independently selected from the group consisting of C5–C30 aryl, C1–C30 alkoxyl, C1–C30 polyalkoxyalkyl, C1–C30 polyhydroxyalkyl, C5–C30 polyhydroxyaryl, C1–C30 aminoalkyl, saccharide, peptide, —CH2(CH2OCH2)b—CH2—, —(CH2)a—CO—, —(CH2)a—CONH, —CH2—(CH2OCH2)b—CH2—CONH—, —(CH2)a—NHCO—, —CH2—(CH2OCH2)b—CH2—NHCO—, —(CH2)a—O—, and —CH2—(CH2OCH2)b—CO—;
- X1 and X2 are single bonds, or are independently selected from the group consisting of nitrogen, saccharide, —CR14—, —CR14R15, —NR16R17;
- C5–C30 aryl;
- Q is a single bond or is selected from the group consisting of —O—, —S—, —Se—, and —NR16;
- a1 and b1 independently vary from 0 to 5;
- R12, R13, and R18 to R31 are independently selected from the group consisting of hydrogen, C1–C10 alkyl, C5–C20 aryl, C1–C10 alkoxyl, C1–C10 polyalkoxyalkyl, C1–C20 polyhydroxyalkyl, C5–C20 polyhydroxyaryl, C1–C10 aminoalkyl, cyano, nitro, halogen, saccharide, peptide, —CH2(CH2OCH2)b—CH2—OH, —(CH2)a—CO2H, —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—OH and —CH2—(CH2OCH2)b—CO2H;
- R14 to R17 are independently selected from the group consisting of hydrogen, C1–C10 alkyl, C5–C20 aryl, C1–C10 alkoxyl, C1–C10 polyalkoxyalkyl, C1–C20 polyhydroxyalkyl, C5–C20 polyhydroxyaryl, C1–C10 aminoalkyl, saccharide, peptide, —CH2(CH2OCH2)b—CH2—, —(CH2)a—CO—, —(CH2)a—CONH—, —CH2—(CH2OCH2)b—CH2—CONH—, —(CH2)a—NHCO—, —CH2—(CH2OCH2)b—CH2—NHCO—, —(CH2)a—O—, and —CH2—(CH2OCH2)b—CO—;
- Bm and Dm are independently selected from the group consisting of bioactive peptide, protein, cell, antibody, antibody fragment, saccharide, glycopeptide, peptidomimetic, drug, drug mimic, hormone, metal chelating agent, radioactive or nonradioactive metal complex, echogenic agent, photoactive molecule, and phototherapy agent;
- a and c independently vary from 1 to 20;
- b and d independently vary from 1 to 100.
9 more elements
A method for performing a diagnostic and therapeutic procedure comprising administering to an individual an effective amount of the composition of cyanine dye bioconjugate of Formula 2
- wherein W1 and W2 are S;
- Y1, Y2, Z1, and Z2 are independently selected from the group consisting of hydrogen, tumor-specific agent, phototherapy agent, —CONH-Bm, —NHCO-Bm, —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—N(R12)—(CH2)b—CONH-Bm, —(CH2)a—N(R12)—(CH2)c—NHCO-Bm, —(CH2)a—N(R12)—CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—N(R12)—CH2—(CH2OCH2)b—CH2—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—N(R12)—(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—N(R12)—(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—N(R12)—CH2—(CH2OCH2)d—CONH-Bm, —CH2—(CH2OCH2)b—CH2—N(R12)—CH2—(CH2OCH2)d—NHCO-Bm, —CONH-Dm, —NHCO-Dm, —(CH2)a—CONH-Dm, —CH2—(CH2OCH2)b—CH2—CONH-Dm, —(CH2)a—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—NHCO-Dm, —(CH2)a—N(R12)—(CH2)b—CONH-Dm, —(CH2)a—N(R12)—(CH2)c—NHCO-Dm, —(CH2)a—N(R12)—CH2—(CH2OCH2)b—CH2—CONH-Dm, —(CH2)a—N(R12)—CH2—(CH2OCH2)b—CH2—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—N(R12)—(CH2)a—CONH-Dm, —CH2—(CH2OCH2)b—CH2—N(R12)—(CH2)a—NHCO-Dm, —CH2—(CH2OCH2)b—CH2—N(R12)—CH2—(CH2OCH2)d—CONH-Dm, —CH2—(CH2OCH2)b—CH2—N(R12)—CH2—(CH2OCH2)d—NHCO-Dm, —(CH2)a—N R12R13, and —CH2(CH2OCH2)b—CH2N R12R13;
- K1 and K2 are independently selected from the group consisting of C1–C30 alkyl, C5–C30 aryl, C1–C30 alkoxyl, C1–C30 polyalkoxyalkyl, C1–C30 polyhydroxyalkyl, C5–C30 polyhydroxyaryl, C1–C30 aminoalkyl, saccharide, peptide, —CH2(CH2OCH2)b—CH2—, —(CH2)a—CO—, —(CH2)a—CONH, —CH2—(CH2OCH2)b—CH2—CONH—, —(CH2)a—NHCO—, —CH2—(CH2OCH2)b—CH2—NHCO—, —(CH2)a—O—, and —CH2—(CH2OCH2)b—CO—;
- X1 and X2 are single bonds, or are independently selected from the group consisting of nitrogen, saccharide, —CR14—, —CR14R15, —NR16R17;
- C5–C30 aryl;
- Q is a single bond or is selected from the group consisting of —O—, —S—, —Se—, and —NR18;
- a1 and b1 independently vary from 0 to 5;
- R12, R13, and R18 to R31 are independently selected from the group consisting of hydrogen, C1–C10 alkyl, C5–C20 aryl, C1–C10 alkoxyl, C1–C10 polyalkoxyalkyl, C1–C20 polyhydroxyalkyl, C5–C20 polyhydroxyaryl, C1–C10 aminoalkyl, cyano, nitro, halogen, saccharide, peptide, —CH2(CH2OCH2)b—CH2—OH, —(CH2)a—CO2H, —(CH2)a—CONH-Bm, —CH2—(CH2OCH2)b—CH2—CONH-Bm, —(CH2)a—NHCO-Bm, —CH2—(CH2OCH2)b—CH2—NHCO-Bm, —(CH2)a—OH and —CH2—(CH2OCH2)b—CO2H;
- R14 to R17 are independently selected from the group consisting of hydrogen, C1–C10 alkyl, C5–C20 aryl, C1–C10 alkoxyl, C1–C10 polyalkoxyalkyl, C1–C20 polyhydroxyalkyl, C5–C20 polyhydroxyaryl, C1–C10 aminoalkyl, saccharide, peptide, —CH2(CH2OCH2)b—CH2—, —(CH2)a—CO—, —(CH2)a—CONH, —CH2—(CH2OCH2)b—CH2—CONH—, —(CH2)a—NHCO—, —CH2—(CH2OCH2)b—CH2—NHCO—, —(CH2)a—O—, and —CH2—(CH2OCH2)b—CO—;
- Bm and Dm are independently selected from the group consisting of bioactive peptide, protein, cell, antibody, antibody fragment, saccharide, glycopeptide, peptidomimetic, drug, drug mimic, hormone, metal chelating agent, radioactive or nonradioactive metal complex, echogenic agent, photoactive molecule, and phototherapy agent;
- a and c independently vary from 1 to 20;
- b and d independently vary from 1 to 100;
- and
- thereafter, performing said procedure.
11 more elements
Dependencies are inferred from the claim text.