Molecular renal probes for detecting acute kidney injury

Patent metadata

Field	Value
Publication number	US-12296027-B2
Application number	US-202017420666-A
Country	US
Kind code	B2
Filing date	Jan 31, 2020
Priority date	Feb 1, 2019
Publication date	May 13, 2025
Grant date	May 13, 2025

Abstract

Disclosed herein are compounds or salts and/or solvates of formula I, II and III, where the compounds or salts and/or solvates have the following structures: (X) a —Y—(Z) b I; II; or X′—Y′ III; where X, Y, Z, X′, Y′, a, b, R 4 , R 6 and R 7 are as defined herein.

First claim

The invention claimed is:

1. A compound of formula I:
(X) a —Y—(Z) b   I

where:
X is selected from:

where R 1 represents a biomarker reactive moiety conjugated to a self-immolative moiety

wherein the self-immolative moiety is selected from:

where the heteroatom directly bonded to the aromatic ring represents the point of attachment to Y and the other heteroatoms represent the point of attachment to a biomarker reactive moiety or are H, provided that at least one of the other heteroatoms is attached to a biomarker reactive moiety;
R 2 represents a point of attachment to Y and R 2′ represents another point of attachment to the same Y group or a point of attachment to a second Y group;
R 3 represents H, SO 3 H or COOH;
Z is selected from:

R 4 is selected from:

where the wavy line represents the point of attachment to the rest of the molecule;
R 4′ represents the point of attachment to Y;
each Y is selected from:

where the wavy line represents the point of attachment to X or Z,

where the wavy line represents the point of attachment to X or Z,

where each R 5 is independently selected from H, CH 2 CHOHCH 3 , CH 2 CCH, and

where the left-hand wavy line (adjacent to m) represents the point of attachment to X or Z and the right-hand wavy line represents the point of attachment to the rest of the molecule;
a is 0 or 1 and b is 1, provided that:
at least one of a and b is 1; and
when a and b are both 1, Y is selected from:

or pharmaceutically acceptable salts and/or solvates thereof, provided that when X is

then Z is 0.

2. The compound or salts and/or solvates thereof according to claim 1 , wherein the biomarker reactive moiety is selected from:

where the wavy line is the point of attachment to the rest of the molecule or, the self-immolative moiety.

3. The compound or salts and/or solvates thereof according claim 1 , wherein X, when present, is selected from:

4. The compound or salts and/or solvates thereof according claim 1 , wherein X, when present, is:

where R 3 is H.

5. The compound or salts and/or solvates thereof according to claim 1 , wherein the biomarker reactive moiety is selected from:

6. The compound or salts and/or solvates thereof according to claim 1 wherein Z is:

7. The compound or salts and/or solvates thereof according claim 1 , wherein
(ai) R 4 , when present, is

and/or
(aii) each R 5 , when present, is independently selected from H, CH 2 CHOHCH 3 and

where the left-hand wavy line (adjacent to m) represents the point of attachment to X or Z and the right-hand wavy line represents the point of attachment to the rest of the molecule.

8. The compound or salts and/or solvates thereof according to claim 1 , wherein a is 1 and Y is

9. The compound or salts and/or solvates thereof according to claim 1 , wherein:
a is 1, X is

where R 3 is H, the biomarker reactive moiety is:

Z is

where R 4 is,

and Y is

where n is 7.

10. A compound according to formula II:

where:
R 4 is selected from:

where the wavy line represents the point of attachment to the rest of the molecule;
R 6 is OH or OC 1 -C 6 alkyl;
R 7 is:

or pharmaceutically acceptable salts and/or solvates thereof.

Assignees

• Univ Nanyang Tech

Inventors

• Pu Kanyi
• Huang Jiaguo

Classifications

• G01N2800/347

  Renal failures; Glomerular diseases; Tubulointerstitial diseases, e.g. nephritic syndrome, glomerulonephritis; Renovascular diseases, e.g. renal artery occlusion, nephropathy · CPC title

• G01N33/583

  with non-fluorescent dye label · CPC title

• G01N33/533

  with fluorescent label · CPC title

• A61K49/0039

  Coumarin dyes · CPC title

• A61B5/201

  Assessing renal or kidney functions · CPC title