US 12,296,027 B2
Molecular renal probes for detecting acute kidney injury
Kanyi Pu, Singapore (SG); and Jiaguo Huang, Singapore (SG)
Assigned to Nanyang Technological University, Singapore (SG)
Appl. No. 17/420,666
Filed by Nanyang Technological University, Singapore (SG)
PCT Filed Jan. 31, 2020, PCT No. PCT/SG2020/050049
§ 371(c)(1), (2) Date Jul. 2, 2021,
PCT Pub. No. WO2020/159448, PCT Pub. Date Aug. 6, 2020.
Claims priority of application No. 10201900965U (SG), filed on Feb. 1, 2019.
Prior Publication US 2022/0096662 A1, Mar. 31, 2022
Int. Cl. A61K 49/00 (2006.01); A61B 5/20 (2006.01); G01N 33/533 (2006.01); G01N 33/58 (2006.01)
CPC A61K 49/0032 (2013.01) [A61B 5/201 (2013.01); A61K 49/0039 (2013.01); G01N 33/533 (2013.01); G01N 33/583 (2013.01); G01N 2800/347 (2013.01)] 10 Claims
 
1. A compound of formula I:
(X)a—Y—(Z)b  I
where:
X is selected from:

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where R1 represents a biomarker reactive moiety conjugated to a self-immolative moiety

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wherein the self-immolative moiety is selected from:

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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;
R2 represents a point of attachment to Y and R2′ represents another point of attachment to the same Y group or a point of attachment to a second Y group;
R3 represents H, SO3H or COOH;
Z is selected from:

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R4 is selected from:

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where the wavy line represents the point of attachment to the rest of the molecule;
R4′ represents the point of attachment to Y;
each Y is selected from:

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

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

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where each R5 is independently selected from H, CH2CHOHCH3, CH2CCH, and

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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:

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

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then Z is 0.