Var2csa-drug conjugates

A compound of Formula I:

• T-L-P I
• wherein:
• T is a targeting moiety comprising a VAR2CSA polypeptide, and
• L-P is L1-P1 or L2-P2;
• wherein:
• L1 is a linker, or L1 is absent;
• P1 is a monovalent radical of a compound of Formula XIV
• wherein:
• R16 and R17 are each independently H or a saturated or unsaturated moiety having a linear, branched, or non-aromatic cyclic skeleton containing one to ten carbon atoms, and the carbon atoms are optionally substituted with:
• —OH, —I, —Br, —Cl, —F, —CN, —CO2H, —CHO, —COSH, or —NO2;
• or R17 and R20 are fused and form a ring;
• R18 and R19 are independently selected from the group consisting of:
• H, R25, and ArR25—, or R18 and R19 are joined to form a ring, wherein the ring formed by joining R18 and R19 is a three to seven member non-aromatic cyclic skeleton within the definition of R25;
• R20 is selected from the group consisting of:
• H, R25, ArR25—, and Ar;
• or R20 and R17 are fused and form a ring;
• R21 is selected from the group consisting of:
• H, R25, and ArR25—;
• R22 and R23 are independently selected from the group consisting of:
• H, R25, and ArR25—;
• R24 is:
• —Y—(CO)NHSO2—R26;
• R25 is a saturated or unsaturated moiety having a linear, branched, or non-aromatic cyclic skeleton containing one to ten carbon atoms, zero to four nitrogen atoms, zero to four oxygen atoms, and zero to four sulfur atoms, and the carbon atoms are optionally substituted with:
• ═O, ═S, OH, —OR28, —O2CR28, —SH, —SR28, —SOCR28, —NH2, —NHR28, —N(R28)2, —NHCOR28, —NR28COR28, —I, —Br, —Cl, —F, —CN, —CO2H, —CO2R28, —CHO, —COR28, —CONH2, —CONHR28, —CON(R28)2, —COSH, —COSR28, —NO2, —SO3H, —SOR28, or —SO2R28, wherein R28 is a linear, branched or cyclic, one to ten carbon saturated or unsaturated alkyl group;
• Y is a linear, saturated or unsaturated, one to six carbon alkyl group, optionally substituted with R25, ArR25—, or X;
• X is selected from the group consisting of:
• —OH, —OR25, ═O, ═S, —O2CR25, —SH, —SR25, —SOCR25, —NH2, —NHR25, —N(R25)2, —NHCOR25, —NRCOR25, —I, —Br, —Cl, —F, —CN, —CO2H, —CO2R25, —CHO, —COR25, —CONH2, —CONHR25, —CON(R25)2, —COSH, —COSR25, —NO2, —SO3H, —SOR25, and —SO2R25 and
• R26 is selected from the group consisting of optionally substituted alkyl, optionally substituted alkylamino, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl and optionally substituted heteroaryl, —COR27, —CSR27, —OR27, and —NHR27, wherein each R27 is, independently, optionally substituted alkyl, optionally substituted alkylamino, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl or optionally substituted heteroaryl;
• and
• wherein:
• L2 is a linker;
• P2 is a cytotoxic compound;
• and
• L2-P2 has the following structure (III):
• wherein:
• R is selected from the group consisting of optionally substituted alkyl, optionally substituted alkylamino, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —COR27, —CSR27, —OR27, and —NHR27, wherein each R27 is, independently, optionally substituted alkyl, optionally substituted alkylamino, optionally substituted cycloalkyl, optionally substituted aryl, optionally substituted heterocyclyl and optionally substituted heteroaryl, or R is absent;
• P3 is the remaining portion of compound P2;
• and
• L3 is the remaining portion of linker L2 or is absent.