US 11,938,201 B2
Imaging and radiotherapeutics agents targeting fibroblast-activation protein-alpha (FAP-alpha)
Xing Yang, Baltimore, MD (US); Sridhar Nimmagadda, Baltimore, MD (US); Steven Rowe, Parkville, MA (US); Stephanie Slania, Baltimore, MD (US); and Martin G. Pomper, Baltimore, MD (US)
Assigned to The Johns Hopkins University, Baltimore, MD (US)
Filed by The Johns Hopkins University, Baltimore, MD (US)
Filed on Jul. 18, 2023, as Appl. No. 18/354,282.
Application 18/354,282 is a continuation of application No. 16/758,182, previously published as PCT/US2018/057086, filed on Oct. 23, 2018.
Claims priority of provisional application 62/575,607, filed on Oct. 23, 2017.
Prior Publication US 2023/0364274 A1, Nov. 16, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 51/00 (2006.01); A61K 47/54 (2017.01); A61K 51/04 (2006.01); A61M 36/14 (2006.01)
CPC A61K 51/0485 (2013.01) [A61K 47/545 (2017.08); A61K 51/0478 (2013.01); A61K 51/0482 (2013.01)] 3 Claims
 
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:

OG Complex Work Unit Chemistry
wherein:
R1x and R2x are each independently selected from the group consisting of H, OH, halogen, C1-6alkyl, —O—C1-6alkyl, and —S—C1-6alkyl;
R3x 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)2aryl, —CO2H, —SO3H, —SO2NH2, —PO3H2, and 5-tetrazolyl;
R4x is H;
R5x, R6x, and R7x are each independently selected from the group consisting of H, —OH, oxo, halogen, —C1-6alkyl, —O—C1-6alkyl, —S—C1-6alkyl, —NR8xR9x, —OR12x, —Het2 and —Ar2 each of C1-6 alkyl being optionally substituted with from 1 to 3 substituents selected from —OH and halogen;
R8x, R9x, and R12x are each independently selected from the group consisting of H, —OH, halo, —C1-6alkyl, —O—C1-6alkyl, —S—C1-6alkyl, and —Ar3;
R10x, R11x, R13x and R14x are each independently selected from the group consisting of H, —OH, halogen, —C1-6alkyl, —O—C1-6alkyl, and —S—C1-6alkyl; Ar1, Ar2 and Ar3 are each independently a 5- or 6-membered aromatic monocycle optionally comprising 1 or 2 heteroatoms selected from O, N and S; each of Ar1, Ar2 and Ar3 being optionally and independently substituted with from 1 to 3 substituents selected from —NR10xR11x, —C1-6alkyl, —O—C1-6alkyl, and —S—C1-6alkyl;
Het2 is a 5- or 6-membered non-aromatic monocycle optionally comprising 1 or 2 heteroatoms selected from O, N and S; Het2 being optionally substituted with from 1 to 3 substituents selected from —NR13xR14x, —C1-6alkyl, —O—C1-6alkyl, and —S—C1-6alkyl;
v is 0, 1, 2, or 3; and

OG Complex Work Unit Chemistry
represents a 5 to 10-membered N-containing aromatic or non-aromatic mono- or bicyclic heterocycle, said heterocycle optionally further comprising 1, 2 or 3 heteroatoms selected from O, N and S;
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.