US 11,925,655 B2
FAP-activated therapeutic agents, and uses related thereto
William W. Bachovchin, Cambridge, MA (US); Hung-sen Lai, Andover, MA (US); David G. Sanford, Reading, MA (US); Sarah E. Poplawski, Belmont, MA (US); and Wengen Wu, Winchester, MA (US)
Assigned to Bach Biosciences, LLC, Cambridge, MA (US)
Filed by Bach Biosciences, LLC, Cambridge, MA (US)
Filed on Mar. 4, 2022, as Appl. No. 17/653,565.
Application 17/653,565 is a continuation of application No. 16/894,227, filed on Jun. 5, 2020, granted, now 11,266,669.
Application 16/894,227 is a continuation of application No. 16/161,170, filed on Oct. 16, 2018, granted, now 10,709,722, issued on Jul. 14, 2020.
Application 16/161,170 is a continuation of application No. 15/655,317, filed on Jul. 20, 2017, granted, now 10,117,887, issued on Nov. 6, 2018.
Application 15/655,317 is a continuation of application No. 15/318,607, granted, now 9,737,556, issued on Aug. 22, 2017, previously published as PCT/US2015/035800, filed on Jun. 15, 2015.
Claims priority of provisional application 62/012,003, filed on Jun. 13, 2014.
Prior Publication US 2022/0296621 A1, Sep. 22, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/62 (2017.01); A61K 31/704 (2006.01); A61K 47/54 (2017.01); A61K 47/64 (2017.01)
CPC A61K 31/704 (2013.01) [A61K 47/545 (2017.08); A61K 47/62 (2017.08); A61K 47/64 (2017.08)] 20 Claims
 
1. A method of treating a disorder in which fibroblast activation protein (FAP) is upregulated, comprising administering to a subject in need thereof a therapeutically effective amount of:
(i) a prodrug represented by Formula I:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
R1 represents (C1-C10)alkyl, (C1-C10)alkoxy, (C1-C10)alkyl-C(O)—(C1-C10)alkyl, (C3-C3)cycloalkyl, (C3-C3)cycloalkyl(C1-C10)alkyl, aryl, aryl(C1-C10)alkyl, heteroaryl, or heteroaryl(C1-C10)alkyl, wherein any R1 is optionally substituted with one or more substituents independently selected from the group consisting of halo, hydroxy, carboxylate, cyano, amino, nitro, and —SH; or

OG Complex Work Unit Chemistry
represents an N-terminally blocked alpha amino acid residue, wherein X is O;
R2 represents H or a (C1-C6)alkyl;
R3 represents a (C1-C6)alkyl;
R4 is absent or represents a (C1-C6)alkyl, —OH, —NH2, or halogen;
X represents O or S;
L represents a bond, or —N(H)-L- represents a self-immolative linker; and
Cyt′ represents a radical of an anthracycline or derivative thereof; and
(ii) an additional therapeutic agent.