Dual-sensitizer-containing luminescent compounds, conjugates, and uses thereof

Patent metadata

Field	Value
Publication number	US-9415111-B2
Application number	US-37719907-A
Country	US
Kind code	B2
Filing date	Aug 11, 2007
Priority date	Aug 11, 2006
Publication date	Aug 16, 2016
Grant date	Aug 16, 2016

Abstract

The invention relates to novel luminescent compositions of matter containing two fluorophores (sensitizers), synthetic methods for making the compositions, macromolecular conjugates of the compositions, and the use of the compositions and their conjugates in various methods of detection. The invention also provides kits containing the compositions and their conjugates for use in the methods of detection.

First claim

What is claimed is:

1. A composition of matter comprising:
(i) a first sensitizer moiety having Formula (I) or (II);
(ii) a chelating moiety selected from EDTA, DTPA, TTHA, DOTA, TAGA, DOTP, DTPA-BMA, DO2P, and HP-DO3A covalently joined, optionally through a first linker independently selected from —NH— and a heterocyclic alkylene moiety having the formula

to the first sensitizer; and
(iii) a second sensitizer moiety having the Formula (II) covalently joined, through a second linker having the formula

to the chelating moiety of (ii);
wherein Formula (I) is:

and wherein:
X is CH—R 1 , S, or N—R 1 ;
R 1 is H; a linear alkylene (C 1 -C 20 ), a branched alkylene (C 3 -C 20 ), a cyclic alkylene (C 3 -C 10 ), a linear alkenylene (C 2 -C 20 ), a branched alkenylene (C 3 -C 20 ), a cyclic alkenylene (C 3 -C 10 ), a linear alkynylene (C 2 -C 20 ), a branched alkynylene (C 3 -C 20 ), a cyclic alkynylene (C 3 -C 10 ), an arene (C 6 -C 19 ), an alkylarene having a C 1 -C 20 alkyl portion and a C 6 -C 19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O;
R 2 is H; NH 2 ; carboxamide; hydrazide; acylhydrazide or alkylhydrazide; hydroxamate; COOH; CO—R′ or CO—O—R′, where R′ is a linear alkylene (C 1 -C 20 ), a branched alkylene (C 3 -C 20 ), a cyclic alkylene (C 3 -C 10 ), a linear alkenylene (C 2 -C 20 ), a branched alkenylene (C 3 -C 20 ), a cyclic alkenylene (C 3 -C 10 ), a linear alkynylene (C 2 -C 20 ), a branched alkynylene (C 3 -C 20 ), a cyclic alkynylene (C 3 -C 10 ), an arene (C 6 -C 19 ), an alkylarene having a C 1 -C 20 alkyl portion and a C 6 -C 19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O;
R 3 is a linear alkylene (C 1 -C 20 ), a branched alkylene (C 3 -C 20 ), a cyclic alkylene (C 3 -C 10 ), a linear alkenylene (C 2 -C 20 ), a branched alkenylene (C 3 -C 20 ), a cyclic alkenylene (C 3 -C 10 ), a linear alkynylene (C 2 -C 20 ), a branched alkynylene (C 3 -C 20 ), a cyclic alkynylene (C 3 -C 10 ), an arene (C 6 -C 19 ), an alkylarene having a C 1 -C 20 alkyl portion and a C 6 -C 19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O; and wherein the linear, branched, or cyclic alkylene, alkenylene, alkynylene, heteroalkylene, arene, or alkylarene moieties are optionally further substituted with from 1-3 halo atoms; and
wherein the

at position 7 of the phenyl ring indicates the site of covalent attachment, optionally through the first linker, of the sensitizer moiety to the chelating moiety; and
wherein Formula (II) is:

and wherein:
Z is a CH—R 4 , S, or N—R 4 ;
R 4 is H; a linear alkylene (C 1 -C 20 ), a branched alkylene (C 3 -C 20 ), a cyclic alkylene (C 3 -C 10 ), a linear alkenylene (C 2 -C 20 ), a branched alkenylene (C 3 -C 20 ), a cyclic alkenylene (C 3 -C 10 ), a linear alkynylene (C 2 -C 20 ), a branched alkynylene (C 3 -C 20 ), a cyclic alkynylene (C 3 -C 10 ), an arene (C 6 -C 19 ), an alkylarene having a C 1 -C 20 alkyl portion and a C 6 -C 19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O; and wherein the linear, branched, or cyclic alkylene, alkenylene, alkynylene, heteroalkylene, arene, or alkylarene moieties are optionally further substituted with from 1-3 halo atoms;
R 5 is carboxamide; hydrazide; acylhydrazide or alkylhydrazide; hydroxamate; COOH; CO—R′ or CO—O—R′, where R′ is a linear alkylene (C 1 -C 20 ), a branched alkylene (C 3 -C 20 ), a cyclic alkylene (C 3 -C 10 ), a linear alkenylene (C 2 -C 20 ), a branched alkenylene (C 3 -C 20 ), a cyclic alkenylene (C 3 -C 10 ), a linear alkynylene (C 2 -C 20 ), a branched alkynylene (C 3 -C 20 ), a cyclic alkynylene (C 3 -C 10 ), an arene (C 6 -C 19 ), an alkylarene having a C 1 -C 20 alkyl portion and a C 6 -C 19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O; and
R 6 is H; a halogen; a linear alkylene (C 1 -C 20 ), a branched alkylene (C 3 -C 20 ), a cyclic alkylene (C 3 -C 10 ), a linear alkenylene (C 2 -C 20 ), a branched alkenylene (C 3 -C 20 ), a cyclic alkenylene (C 3 -C 10 ), a linear alkynylene (C 2 -C 20 ), a branched alkynylene (C 3 -C 20 ), a cyclic alkynylene (C 3 -C 10 ), an arene (C 6 -C 19 ), an alkylarene having a C 1 -C 20 alkyl portion and a C 6 -C 19 arene portion, a linear heteroalkylene (2-20 atoms), a branched heteroalkylene (3-20 atoms), or a cyclic heteroalkylene (3-10 atoms), wherein at least one atom of the heteroalkylene is N or O; and wherein the linear, branched, or cyclic alkylene, alkenylene, alkynylene, heteroalkylene, arene or alkylarene moieties are optionally further substituted with from 1-3 halo atoms; and wherein the

at position 7 of the phenyl ring indicates the site of covalent attachment, through the second linker, of the sensitizer moiety to the chelating moiety.

2. The composition of claim 1 , wherein X is N—R 1 .

3. The composition of claim 2 , wherein R 3 is CH 3 .

4. The composition of claim 3 , wherein said first sensitizer moiety has the formula:

5. The composition of claim 2 , wherein R 3 is CF 3 .

6. The composition of claim 5 wherein said first sensitizer moiety has the formula:

7. The composition of claim 2 , wherein R 1 is H.

8. The composition of claim 7 , wherein R 3 is CF 3 .

9. The composition of claim 8 , wherein said first sensitizer moiety has the formula:

10. The composition of claim 1 , wherein the Z is N—R 4 .

11. The composition of claim 10 , wherein R 4 is a cyclopropyl moiety.

12. The composition of claim 11 , wherein R 5 is an organic acid moiety having the formula COOH.

13. The composition of claim 11 , wherein R 6 is an F atom.

14. The composition of claim 13 , wherein said second sensitizer moiety has the formula:

15. The composition of claim 1 , wherein the chelating moiety is selected from the group consisting of: TTHA, DOTA, TAGA, DOTP, DTPA-BMA, DO2P, and HP-DO3A.

16. The composition of claim 1

Assignees

• Mustaev Arkady
• Marras Salvatore A E
• Univ Rutgers

Inventors

• Mustaev Arkady
• Marras Salvatore A E

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61K49/0021

  the fluorescent group being a small organic molecule · CPC title

• A61K47/55

  the modifying agent being also a pharmacologically or therapeutically active agent, i.e. the entire conjugate being a codrug · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title