Application of reduced dyes in imaging

Patent metadata

Field	Value
Publication number	US-9470691-B2
Application number	US-201414192827-A
Country	US
Kind code	B2
Filing date	Feb 27, 2014
Priority date	Sep 23, 2011
Publication date	Oct 18, 2016
Grant date	Oct 18, 2016

Abstract

The present invention provides novel compounds and methods for hydrocyanines derived from near-infrared cyanine dyes, as reactive oxygen species probes in imaging. In certain embodiments, the present invention provides reduced dyes as substrates for ELISA and Western blots.

First claim

What is claimed is:

1. A compound having Formula I:

wherein
each R 1 is an independently selected alkyl group that is additionally substituted with from 0 to 1 R 14 and from 0 to 1 -L-Y—Z; wherein the alkyl is optionally interrupted by at least one heteroatom or an ionic group;
R 1a is either hydrogen or deuterium;
each R 2a and R 2b is a member independently selected from the group consisting of alkyl, alkenyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, amidoalkyl, alkylthioalkyl, carboxyalkyl, alkoxycarbonylalkyl, or sulfonatoalkyl; wherein a carbon of the member is additionally substituted with from 0 to 1 -L-Y—Z;
each R 3 , R 4 , R 5 , and R 6 is a member independently selected from the group consisting of hydrogen, alkyl, alkenyl, halo, hydroxyl, alkoxy, amino, cyano, carboxyl, alkoxycarbonyl, amido, sulfonato, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, and sulfonatoalkyl; wherein a carbon of the member is additionally substituted with from 0 to 1 -L-Y—Z;
R 8 , R 9 , R 10 , R 11 and R 12 are each a member independently selected from the group consisting of hydrogen, alkyl, alkenyl, halo, alkoxy, sulfonato, hydroxyl, amino, carboxyl, alkoxycarbonyl, cyano, amido, thioacetyl, and -L-Y—Z; wherein at least one member selected from the group consisting of R 8 , R 9 , and R 10 is halo;
each R 13 is a member independently selected from the group consisting of hydroxyl, amino, carboxyl, and alkoxycarbonyl;
each R 14 is a member independently selected from the group consisting of alkyl, alkenyl, halo, hydroxyl, alkoxy, amino, amido, amidoalkyl, cyano, cyanoalkyl, carboxyl, alkoxycarbonyl, amido, sulfonato, sulfonatoalkyl, thioacetyl, thioacetylalkyl, alkoxycarbonylalkyl, and alkoxyalkyl; wherein the alkyl or alkenyl is additionally substituted with from 0 to 1 R 13 and from 0 to 1 -L-Y—Z;
each L is an optional member independently selected from the group consisting of a bond, a C 1 -C 20 alkylene, and a C 1 -C 20 alkenylene; wherein the alkylene or alkenylene is optionally interrupted by at least one heteroatom;
each Y is an optional member independently selected from the group consisting of a bond, —O—, —S—, —NH—, —NHC(O)—, —C(O)NH—, —NR 15 —, —NR 15 C(O)—, —C(O)NR 15 —, —N(Z)—, —N(Z)C(O)—, and —C(O)N(Z)—;
each Z is independently selected from the group consisting of -L-R 13 and -L-R 16 ;
or alternatively, —Y—Z is a member selected from the group consisting of —N(Z 1 ) 2 , —N(Z 1 )C(O)Z 1 , and —C(O)N(Z 1 ) 2 , and the two Z 1 groups are linked to form a cycloalkynyl group;
each R 15 is a member independently selected from the group consisting of alkyl and alkoxycarbonylalkyl; wherein the alkyl is optionally interrupted by at least one heteroatom;
each R 16 is independently a member selected from the group consisting of activated acyl, acrylamido, optionally substituted alkylsulfonate ester, azido, optionally substituted arylsulfonate ester, optionally substituted amino, aziridino, boronato, cycloalkynyl, cycloalkynylcarbonyl, diazo, formyl, glycidyl, halo, haloacetamidyl, haloalkyl, haloplatinato, halotriazino, hydrazinyl, imido ester, isocyanato, isothiocyanato, maleimidyl, mercapto, phosphoramidityl, a photoactivatable moiety, vinyl sulfonyl, alkynyl, cycloalkynyl, spirocycloalkynyl, a pegylated azido, a pegylated alkynyl, a pegylated cycloalkynyl, a pegylated spirocycloalkynyl, an o-diarylphosphino aryl ester, and an ortho substituted phosphine oxide aryl ester; and
wherein said compound has a balanced charge.

2. The compound of claim 1 , wherein each R 16 is independently a member selected from the group consisting of activated acyl, acrylamido, optionally substituted alkylsulfonate ester, azido, optionally substituted arylsulfonate ester, amino, aziridino, boronato, diazo, formyl, glycidyl, halo, haloacetamidyl, haloalkyl, haloplatinato, halotriazino, hydrazinyl, imido ester, isocyanato, isothiocyanato, maleimidyl, mercapto, phosphoramidityl, a photoactivatable moiety, and vinyl sulfonyl.

3. The compound of claim 1 , wherein at least one R 16 is a member independently selected from the group consisting of azido, alkynyl, cycloalkynyl, a pegylated azido, a pegylated alkynyl, a pegylated cycloalkynyl, and an o-diarylphosphino aryl ester.

4. The compound of claim 1 , wherein at least one member selected from the group consisting of R 8 , R 9 , and R 10 is chloro or fluoro.

5. The compound of claim 4 , wherein at least one member selected from the group consisting of R 8 , R 9 , and R 10 is fluoro.

6. The compound of claim 4 , wherein at least one member selected from the group consisting of R 8 , R 9 , and R 10 is chloro.

7. The compound of claim 1 , wherein each R 3 , R 4 , R 5 , and R 6 is a member independently selected from the group consisting of hydrogen, alkyl, alkenyl, halo, alkoxy, cyano, carboxyl, alkoxycarbonyl, amido, sulfonato, alkoxyalkyl, carboxyalkyl, alkoxycarbonylalkyl, and sulfonatoalkyl.

8. The compound of claim 1 , wherein R 1 is (CH 2 ) r SO 3 H or (CH 2 ) r SO 3 − ; and
wherein r is an integer from 1 to 20.

9. The compound of claim 8 , wherein r is 2, 3, or 4.

10. The compound of claim 1 , wherein R 2a and R 2b are methyl.

11. The compound of claim 1 , wherein R 8 , R 9 , or R 10 is -L-Y—Z.

12. The compound of claim 1 , having the formula:

13. The compound of claim 1 , wherein the cycloalkynyl group is a member selected from the group consisting of cyclopentynyl, cyclohexynyl, cyclooctynyl, and dibenzocyclooctynyl (DBCO).

Assignees

• Li Cor Inc

Inventors

• Kundu Kousik
• Padhye Nisha
• Volcheck William

Classifications

• G01N33/575

  for cancer · CPC title

• C09B23/0066

  the polymethine chain being part of a carbocyclic ring,(e.g. benzene, naphtalene, cyclohexene, cyclobutenene-quadratic acid) · CPC title

• C07D209/08 Primary

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring · CPC title

• G01N33/582 Primary

  with fluorescent label · CPC title

• C09B23/0008

  substituted on the polymethine chain · CPC title