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:
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
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.
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