Imaging and radiotherapeutics agents targeting fibroblast-activation protein-α (FAP-α)

Patent metadata

Field	Value
Publication number	US-12115233-B2
Application number	US-202418585905-A
Country	US
Kind code	B2
Filing date	Feb 23, 2024
Priority date	Oct 23, 2017
Publication date	Oct 15, 2024
Grant date	Oct 15, 2024

Abstract

Imaging and radiotherapeutics agents targeting fibroblast-activation protein-α (FAP-α) and their use in imaging and treating FAP-α related diseases and disorders are disclosed.

First claim

That which is claimed:

1. A low molecular weight compound of Formula (I):
B-L-A  (I)

wherein:
A is a targeting moiety for FAP-α, wherein A has the structure of:

wherein:
R 1x and R 2x are each independently selected from the group consisting of H, OH, halogen, C 1-6 alkyl, —O-C 1-6 alkyl, and —S-C 1-6 alkyl;
R 3x is selected from the group consisting of H, —CN, —B (OH) 2 —C(O) alkyl, —C(O)aryl-, —C—C—C(O) aryl, —C—C—S(O) 2 aryl, —CO 2 H, —SO 3 H, —SO 2 NH 2 , —PO 3 H 2 , and 5-tetrazolyl;
R 4x is H;
R 5x , R 6x and R 7x are H;
v is 0; and

represents a quinolinyl ring having a point of attachment to a remainder of the FAP binding moiety at the 4-position of the quinolinyl ring;
B is any optical or radiolabeled functional group suitable for optical imaging, positron-emission tomography (PET) imaging, single-photon emission computed tomography (SPECT) imaging, or radiotherapy; and L is a linker having bi-functionalization adapted to form a chemical bond with B and A; or
a stereoisomer, tautomer, racemate, salt, hydrate, or solvate thereof.

2. The compound of claim 1 , wherein R 1x and R 2x are each independently selected from the group consisting of H and F.

3. The compound of claim 2 , wherein R 3x is —CN.

4. The compound of claim 3 , wherein B comprises a chelating agent.

Assignees

• Univ Johns Hopkins

Inventors

• Yang Xing
• Nimmagadda Sridhar
• Rowe Steven
• Slania Stephanie
• Pomper Martin G

Classifications

• A61K51/0482

  chelates from cyclic ligands, e.g. DOTA · CPC title

• A61K51/0478

  complexes from non-cyclic ligands, e.g. EDTA, MAG3 · CPC title

• A61K47/545

  Heterocyclic compounds (A61K47/558 takes precedence) · CPC title

• A61K51/0497

  conjugates with a carrier being an organic compounds · CPC title

• A61K51/0455 Primary

  having six-membered rings with one nitrogen as the only ring hetero atom · CPC title