IP Library › Patent Application 11371572

Patent Application

App. No. 11/371,572

Diagnostic and therapeutic optical agents

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Patent No.: US None
App. No.: 11/371,572

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Abstract

Disclosed herein are compounds that may be characterized by some as cyanine and indocyanine dye bioconjugates. Compounds disclosed herein may be utilized (e.g., in the form of a pharmaceutically acceptable composition) in a number of medical procedures, such as in the visualization and detection of tumors.

Claims (62)

1 . A compound of the following formula, wherein:

W 3 and X 3 are independently selected from the group consisting of —CR 1 , R 2 , —O—, —NR 3 , —S—, and —Se—;

Y 3 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 5 -C 20 aryl, C 1 -C 10 alkoxyl, C 1 -C 10 polyalkoxyalkyl, C 1 -C 20 polyhydroxyalkyl, C 5 -C 20 polyhydroxyaryl, C 1 -C 10 aminoalkyl, —CH 2 (CH 2 OCH 2 ) b —CH 2 —OH, —(CH 2 ), —CO 2 H, —(CH 2 ) a —CONH-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —CONH-Bm, —(CH 2 ) a —NHCO-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —NHCO-Bm, —(CH 2 ) a —N(R 3 )—(CH 2 ) b —CONH-Bm, —(CH 2 ) a —N(R 3 )—(CH 2 ) c —NHCO-Bm, —(CH 2 ) 6 —N(R 3 )—CH 2 —(CH 2 OCH 2 ) b —CH 2 —CONH-Bm, —(CH 2 ) a —N(R 3 )—CH 2 —(CH 2 OCH 2 ) b —CH 2 —NHCO-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—(CH 2 ) a —CONH-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—(CH 2 ) a —NHCO-Bm, —CH 2 (CH 2 OCH 2 ) b —CH 2 NR 3 R 4 , —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—CH 2 —(CH 2 OCH 2 ) d —CONH-Bm, —(CH 2 ) a —NR 3 R 4 , and —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—CH 2 —(CH 2 OCH 2 ) d —NHCO-Bm;

Z 3 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 5 -C 20 aryl, C 1 -C 10 alkoxyl, C 1 -C 10 polyalkoxyalkyl, C 1 -C 20 polyhydroxyalkyl, C 5 -C 20 polyhydroxyaryl, C 1 -C 10 aminoalkyl, —CH 2 (CH 2 OCH 2 ) b —CH 2 —OH, —(CH 2 ) a —CO 2 H, —(CH 2 ) a —CONH-Dm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —CONH-Dm, —(CH 2 ) a —NHCO-Dm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —NHCO-Dm, —(CH 2 ) a —N(R 3 )—(CH 2 ) b —CONH-Dm, (CH 2 ) a —N(R 3 )—(CH 2 ) c —NHCO-Dm, —(CH 2 ) a —N(R 3 )—CH 2 —(CH 2 OCH 2 ) b —CH 2 —CONH-Dm, —(CH 2 ) a —N(R 3 )—CH 2 —(CH 2 OCH 2 ) b —CH 2 —NHCO-Dm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—(CH 2 ) a —CONH-Dm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—(CH 2 ) a —NHCO-Dm, —CH 2 (CH 2 OCH 2 ) b —CH 2 NR 3 R 4 , —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—CH 2 —(CH 2 OCH 2 ) d —CONH-Dm, —(CH 2 ) a —NR 3 R 4 , and —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—CH 2 —(CH 2 OCH 2 ) d —NHCO-Dm;

A 1 is a single or a double bond;

B 1 , C 1 , and D 1 are independently selected from the group consisting of —O—, —S—, —Se—, —P—, —CR 1 , R 2 , —CR 1 , alkyl, NR 3 , and —C═O;

A 1 , B 1 , C 1 , and D 1 may together form a 6- to 12-membered carbocyclic ring or a 6- to 12-membered heterocyclic ring optionally containing one or more oxygen, nitrogen, or sulfur atom;

a 3 and b 3 independently vary from 0 to 5;

R 1 to R 4 , and R 29 to R 37 are independently selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 5 -C 20 aryl, C 1 -C 10 alkoxyl, C 1 -C 10 polyalkoxyalkyl, C 1 -C 20 polyhydroxyalkyl, C 5 -C 20 polyhydroxyaryl, C 1 -C 10 aminoalkyl, cyano, nitro, halogen, saccharide, peptide, —CH 2 (CH 2 OCH 2 ) b —CH 2 —OH, —(CH 2 ) a —CO 2 H, —(CH 2 ) a —CONH-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —CONH-Bm, —(CH 2 ) a —NHCO-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —NHCO-Bm, —(CH 2 ) a —OH, and —CH 2 —(CH 2 OCH 2 ) b —CO 2 H;

atleast one of Y 3 Z 3 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , and R 37 is a constituent including Bm or Dm, wherein Bm and Dm are independently selected from the group consisting of a peptide, a protein, a cell, an antibody, an antibody fragment, a saccharide, a glycopeptide, a peptidomimetic, a drug, a drug mimic, a hormone, a metal chelating agent, a radioactive or nonradioactive metal complex, a photosensitizer for phototherapy, and an echogenic agent;

a and c are independently from 1 to 20; and

b and d are independently from 1 to 100.

2 . The compound of claim 1 , wherein at least one of Bm and Dm is a peptide.

3 . The compound of claim 1 , wherein at least one of Bm and Dm is Octreotide.

4 . The compound of claim 1 , wherein at least one of Bm and Dm is Octreotate.

5 . The compound of claim 1 , wherein at least one of Bm and Dm is Bombesin.

6 . The compound of claim 1 , wherein at least one of Bm and Dm is Cholecystokinin.

7 . The compound of claim 1 , wherein at least one of Bm and Dm is Neurotensin.

8 . A method of using a compound, the method comprising:

administering to an individual an effective amount of a compound; and

activating the compound using light, the compound being of the following formula, wherein:

W 3 and X 3 are independently selected from the group consisting of —CR 1 R 2 , —O—, —NR 3 , —S—, and —Se—;

Y 3 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 5 -C 20 aryl, C 1 -C 10 alkoxyl, C 1 -C 10 polyalkoxyalkyl, C 1 -C 20 polyhydroxyalkyl, C 5 -C 20 polyhydroxyaryl, C 1 -C 10 aminoalkyl, —CH 2 (CH 2 OCH 2 ) b —CH 2 —OH, —(CH 2 ) a —CO 2 H, —(CH 2 ) a —CONH-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —CONH-Bm, —(CH 2 ) a —NHCO-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —NHCO-Bm, —(CH 2 ) a —N(R 3 )—(CH 2 ) b —CONH-Bm, —(CH 2 ) a —N(R 3 )—(CH 2 ) c —NHCO-Bm, —(CH 2 ) a —N(R 3 )—CH 2 —(CH 2 OCH 2 ) b —CH 2 —CONH-Bm, —(CH 2 ) a —N(R 3 )—CH 2 —(CH 2 OCH 2 ) b —CH 2 —NHCO-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—(CH 2 ) a —CONH-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—(CH 2 ) a —NHCO-Bm, —CH 2 (CH 2 OCH 2 ) b —CH 2 NR 3 R 4 , —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—CH 2 —(CH 2 OCH 2 ) d —CONH-Bm, —(CH 2 ) 8 —NR 3 R 4 , and —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—CH 2 —(CH 2 OCH 2 ) d —NHCO-Bm;

A 1 is a single or a double bond;

B 1 , C 1 , and D 1 may be the same or different and are selected from the group consisting of —O—, —S—, —Se—, —P—, —CR 1 R 2 , —CR 1 , alkyl, NR 3 , and —C═O;

A 1 , B 1 , C 1 , and D 1 may together form a 6- to 12-membered carbocyclic ring or a 6- to 12-membered heterocyclic ring optionally containing one or more oxygen, nitrogen, or sulfur atom;

a 3 and b 3 independently vary from 0 to 5;

at least one of Y 3 Z 3 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , and R 37 is a constituent including Bm or Dm, wherein Bm and Dm are independently selected from the group consisting of a peptide, a protein, a cell, an antibody, an antibody fragment, a saccharide, a glycopeptide, a peptidomimetic, a drug, a drug mimic, a hormone, a metal chelating agent, a radioactive or nonradioactive metal complex, a photosensitizer for phototherapy, and an echogenic agent;

a and c are independently from 1 to 20; and

b and d are independently from 1 to 100.

9 . The method of claim 8 , wherein at least one of Bm and Dm is a peptide.

10 . The method of claim 8 , wherein at least one of Bm and Dm is Octreotide.

11 . The method of claim 8 , wherein at least one of Bm and Dm is Octreotate.

12 . The method of claim 8 , wherein at least one of Bm and Dm is Bombesin.

13 . The method of claim 8 , wherein at least one of Bm and Dm is Cholecystokinin.

14 . The method of claim 8 , wherein at least one of Bm and Dm is Neurotensin.

15 . The method of claim 8 , further comprising adding a biocompatible organic solvent at a concentration of one to fifty percent to the compound to prevent in vivo or in vitro fluorescence quenching.

16 . The method of claim 15 , wherein the compound is dissolved in a medium comprising one to fifty percent dimethyl sulfoxide.

17 . A composition comprising:

a pharmaceutically acceptable carrier or excipient; and

a compound of the following formula, wherein:

W 3 and X 3 are independently selected from the group consisting of —CR 1 R 2 , —O—, —NR 3 , —S—, and —Se—;

Y 3 is selected from the group consisting of hydrogen, C 1 -C 10 alkyl, C 5 -C 20 aryl, C 1 -C 10 alkoxyl, C 1 -C 10 polyalkoxyalkyl, C 1 -C 20 polyhydroxyalkyl, C 5 -C 20 polyhydroxyaryl, C 1 -C 10 aminoalkyl, —CH 2 (CH 2 OCH 2 ) b —CH 2 —OH, —(CH 2 ) a —CO 2 H, —(CH 2 ) a —CONH-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —CONH-Bm, —(CH 2 ) a —NHCO-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —NHCO-Bm, —(CH 2 ) a —N(R 3 )—(CH 2 ) b —CONH-Bm, —(CH 2 ) a —N(R 3 )—(CH 2 ) c —NHCO-Bm, —(CH 2 ) a —N(R 3 )—CH 2 —(CH 2 OCH 2 ) b —CH 2 —CONH-Bm, —(CH 2 ) a —N(R 3 )—CH 2 —(CH 2 OCH 2 ) b —CH 2 —NHCO-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—(CH 2 ) a —CONH-Bm, —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—(CH 2 ) a —NHCO-Bm, —CH 2 (CH 2 OCH 2 ) b —CH 2 NR 3 R 4 , —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—CH 2 —(CH 2 OCH 2 ) d —CONH-Bm, —(CH 2 ) a —NR 3 R 4 , and —CH 2 —(CH 2 OCH 2 ) b —CH 2 —N(R 3 )—CH 2 —(CH 2 OCH 2 ) d —NHCO-Bm;

A 1 is a single or a double bond;

B 1 , C 1 , and D 1 are independently selected from the group consisting of —O—, —S—, —Se—, —P—, —CR 1 R 2 , —CR 1 , alkyl, NR 3 , and —C═O;

A 1 , B 1 , C 1 , and D 1 may together form a 6- to 12-membered carbocyclic ring or a 6- to 12-membered heterocyclic ring optionally containing one or more oxygen, nitrogen, or sulfur atom;

a 3 and b 3 independently vary from 0 to 5;

at least one of Y 3 Z 3 , R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , R 35 , R 36 , and R 37 is a constituent including Bm or Dm, wherein Bm and Dm are independently selected from the group consisting of a peptide, a protein, a cell, an antibody, an antibody fragment, a saccharide, a glycopeptide, a peptidomimetic, a drug, a drug mimic, a hormone, a metal chelating agent, a radioactive or nonradioactive metal complex, a photosensitizer for phototherapy, and an echogenic agent;

a and c are independently from 1 to 20; and

b and d are independently from 1 to 100.

18 . The composition of claim 17 , wherein at least one of Bm and Dm is a peptide.

19 . The composition of claim 17 , wherein at least one of Bm and Dm is Octreotide.

20 . The composition of claim 17 , wherein at least one of Bm and Dm is Octreotate.

21 . The composition of claim 17 , wherein at least one of Bm and Dm is Bombesin.

22 . The composition of claim 17 , wherein at least one of Bm and Dm is Cholecystokinin.

23 . The composition of claim 17 , wherein at least one of Bm and Dm is Neurotensin.

24 . The composition of claim 17 , wherein the pharmaceutically acceptable carrier or excipient comprises a biocompatible organic solvent at a concentration of one to fifty percent.

25 . The composition of claim 17 , wherein the pharmaceutically acceptable carrier or excipient comprises one to fifty percent dimethyl sulfoxide.

Assignments (2)

CHANGE OF LEGAL ENTITY Recorded Aug 16, 2011

From: MALLINCKRODT INC.

To: MALLINCKRODT LLC

Reel/Frame 026754/0001 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 9, 2006

From: ACHILEFU, SAMUEL I.; RAJAGOPALAN, RAGHAVAN; DORSHOW, RICHARD B.; BUGAJ, JOSEPH E.

To: MALLINCKRODT INC.

Reel/Frame 017689/0732 →