Benzocyanine compounds

Patent metadata

Field	Value
Publication number	US-9249307-B2
Application number	US-201213571858-A
Country	US
Kind code	B2
Filing date	Aug 10, 2012
Priority date	Aug 16, 2011
Publication date	Feb 2, 2016
Grant date	Feb 2, 2016

Abstract

Compounds useful as labels with properties comparable to known fluorescent compounds. The compounds are conjugated to proteins and nucleic acids for biological imaging and analysis. Synthesis of the compounds, formation and use of the conjugated compounds, and specific non-limiting examples of each are provided.

First claim

What is claimed is:

1. A compound selected from the group consisting of

where
each of R 1 , R 2 , R 5 , and R 6 is the same or different and is independently selected from the group consisting of an aliphatic, heteroaliphatic, sulfoalkyl, heteroaliphatic with terminal SO 3 , a PEG group P—Z where P is selected from an ethylene glycol group, a diethylene glycol group, and a polyethylene glycol group, where the polyethylene glycol group is (CH 2 CH 2 O) s , where s is an integer from 3-6 inclusive, a sulfonamide group -L-SO 2 NH—P—Z, and a carboxamide group -L-CONH—P—Z, where Z is selected from H, CH 3 , a CH 3 group, an alkyl group, or a heteroalkyl group;
each of R 7 , R 8 , R 11 , R 12 , R 13 , and R 14 is the same or different and is independently selected from the group consisting of H, SO 3 , a PEG group P—Z where P is selected from an ethylene glycol group, a diethylene glycol group, and a polyethylene glycol group, where the polyethylene glycol group is (CH 2 CH 2 O) s , where s is an integer from 3-6 inclusive, a sulfonamide-containing group -L-SO 2 NH—P—Z, and a carboxamide-containing group -L-CONH—P—Z, where Z is selected from H, CH 3 , a CH 3 group, an alkyl group, or a heteroalkyl group;
X is selected from —OH, —SH, —NH 2 , —NH—NH 2 , —F, —Cl, —Br, —I, —NHS (hydroxysuccinimidyl/sulfosuccinimidyl), —O-TFP (2,3,5,6-tetrafluorophenoxy), —O-STP (4-sulfo-2,3,5,6-tetrafluorophenoxy), —O-benzotriazole, -benzotriazole, imidazole, azide, —O-carbodiimide, —NR-L-OH, —NR-L-O-phosphoramidite, —NR-L-SH, —NR-L-NH 2 , —NR-L-NH—NH 2 , —NR-L-CO 2 H, —NR-L-CO—NHS, —NR-L-CO-STP, —NR-L-CO-TFP, —NR-L-CO-benzotriazole, —NR-L-CHO, —NR-L-maleimide, —NR-L-NH—CO—CH 2 —I, or —NR-L-NH—CO—CH 2 —Br wherein R is —H or an aliphatic or heteroaliphatic group;
L is selected from a divalent linear (—(CH 2 ) t —, t=0 to 15), crossed, or cyclic alkyl group optionally substituted by at least one oxygen atom and/or sulfur atom;
Kat is a number of Na + , K + , Ca 2+ , ammonia, or other cation(s) needed to compensate the negative charge brought by the cyanine; m is an integer from 0 to 5 inclusive; p is an integer from 1 to 6 inclusive;
each of R3 and R4 is the same or different and is independently hydrogen, an aliphatic group, a heteroaliphatic group, or a PEG group P—Z where P is selected from an ethylene glycol group, a diethylene glycol group, and a polyethylene glycol group, where the polyethylene glycol group is (CH 2 CH 2 O) s , where s is an integer from 3-6 inclusive, and Z is selected from H, a CH 3 group, an alkyl group, or a heteroalkyl group; or R3 and R4 together form a cyclic structure where R3 and R4 are joined using a divalent structural element selected from the group consisting of —(CH 2 ) q —, —(CH 2 ) q O(CH 2 ) q′ —, —(CH 2 ) q S(CH 2 ) q′ —, —(CH 2 ) q CH═CH—, —OCH═CH— where each of q and q′ is the same or different and is a integer from 2 to 6 inclusive; and
Y is selected from the group consisting of hydrogen, alkyl, sulfoalkyl, fluorine, chlorine, bromine, a substituted or unsubstituted aryl-, phenoxy-, phenylmercapto function, and a PEG group P—Z where P is selected from an ethylene glycol group, a diethylene glycol group, and a polyethylene glycol group, where the polyethylene glycol group is (CH 2 CH 2 O) s , where s is an integer from 3-6 inclusive, and Z is selected from H, a CH 3 group, an alkyl group, or a heteroalkyl group.

2. The compound of claim 1 wherein each of R13 and R14 is sulfo.

3. The compound of claim 1 wherein each of R7, R8, R11, and R12 is sulfo.

4. A compound selected from the group consisting of compound V10-04152

and compound V08-15173

5. A kit for detecting at least one biomolecule in a sample, the kit comprising the compound of claim 1 and at least one excipient, and instructions for use of the compound to detect a biomolecule in a sample.

6. The kit of claim 5 wherein the compound is V10-04152 or V08-15173.

Assignees

• Hermanson Greg
• Czerney Peter T
• Desai Surbhi
• Wenzel Matthias S
• Dworecki Boguslawa
• Lehmann Frank G
• Nlend Marie Christine
• Pierce Biotechnology Inc

Inventors

• Hermanson Greg
• Czerney Peter T
• Desai Surbhi
• Wenzel Matthias S
• Dworecki Boguslawa
• Lehmann Frank G
• Nlend Marie Christine

Classifications

• A61K49/0058

  Antibodies · CPC title

• C09B23/083 Primary

  five >CH- groups · CPC title

• A61K49/0034

  Indocyanine green, i.e. ICG, cardiogreen · CPC title

• C09B23/086

  more than five >CH- groups · CPC title

• C09B23/08

  more than three >CH- groups, e.g. polycarbocyanines · CPC title