Near-infrared cyanine dyes and conjugates thereof

Patent metadata

Field	Value
Publication number	US-12187708-B2
Application number	US-202318388604-A
Country	US
Kind code	B2
Filing date	Nov 10, 2023
Priority date	Jun 23, 2020
Publication date	Jan 7, 2025
Grant date	Jan 7, 2025

Abstract

The present invention relates to the field of optical imaging. More particularly, it relates to compounds of the cyanine family with near-infrared emission characterized by improved physico-chemical and biological properties and to conjugates with biological ligands thereof. The invention also relates to the use of these compounds as optical diagnostic agents in imaging or therapy of solid tumors, to the methods for their preparation and to the compositions comprising them.

First claim

The invention claimed is:

1. A compound of formula (II)

wherein
X is direct bond or —O—;
Y is a group selected from linear or branched C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl and heterocyclyl, substituted by at least two hydroxyl groups;
R1 is linear or branched C 1 -C 6 alkyl substituted by a group selected from —SO 3 H, —COOH, —CONH 2 and —COO—C 1 -C 6 alkyl;
R4 is linear or branched C 1 -C 6 alkyl substituted by a group selected from —SO 3 H, —COOH and —CONH—(S) m -T, wherein
S is a spacer;
T is a targeting moiety interacting with an integrin receptor and comprising the sequence Arg-Gly-Asp; and
m is an integer equal to 0 or 1; and

R5 is selected from hydrogen, —SO 3 H, a linear or branched C 1 -C 6 alkyl substituted by —COOH or —CONH—Y, and a group CONH—(S) m -T, wherein Y, S, T and m are defined above;

and wherein at least one between R4 and R5 is linear or branched C 1 -C 6 alkyl substituted by CONH—(S) m -T,
or a stereoisomer or pharmaceutically acceptable salt thereof.

2. The compound of formula (II) according to claim 1 , wherein S is selected from —(CH 2 ) p COO—, —(CH 2 CH 2 O) p CH 2 CH 2 COO— and —(CH 2 CH 2 O) p CH 2 CH 2 NH—, wherein p is an integer between 0 and 20.

3. The compound of formula (II) according to claim 1 , represented by the formula (IIa)

wherein R1, R4, R5 and X are as defined in claim 1 .

4. The compound of formula (II) according to claim 3 which is selected from

5. A method of biomedical optical imaging comprising:
contacting cells or tissues of a mammal with the compound as defined in claim 1 ;
irradiating the cells or tissues at a wavelength absorbed by the compound; and
detecting the near-infrared emission using a fluorescence camera.

6. The method according to claim 5 wherein the biomedical optical imaging is selected from the group consisting of angiography, perfusion imaging, bile duct imaging and nerve imaging.

7. The method according to claim 5 , further comprising demarcating a tumor margin.

8. A pharmaceutical diagnostic composition comprising a compound as defined in claim 1 and at least one pharmaceutically acceptable carrier or excipient.

9. Diagnostic kit comprising at least one compound as defined in claim 1 together with one or more adjuvants.

Assignees

• Bracco Imaging Spa

Inventors

• Blasi Francesco
• Buonsanti Federica
• Crivellin Federico
• Ferraris Andrea
• Orio Laura
• Pizzuto Lorena
• Napolitano Roberta
• Valbusa Giovanni

Classifications

• C09K2211/1051

  with sulfur · CPC title

• C09K2211/1074

  containing more than three nitrogen atoms as heteroatoms · CPC title

• C09K2211/1029

  containing one nitrogen atom as the heteroatom · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title

• C09B23/107

  four >CH- groups · CPC title