Monomethylvaline compounds capable of conjugation to ligands

An antibody-drug conjugate having the formula IIIa:

• or a pharmaceutically acceptable salt thereof, wherein:
• Ab is an antibody that specifically binds to the CD19 antigen
• R17 is selected from the group consisting of C1-C10 alkylene-, —C3-C8 carbocyclo-, —O—(C1-C8-arylene-, —C1-C10 alkylene-arylene-, -arylene-C1-C10 alkylene-, —C1-C10 alkylene-(C3-C8 carbocyclo)-, —(C3-C8 carbocyclo)-C1-C10 alkylene-, —C3-C8 heterocyclo-, —C1-C10 alkylene-(C3-C8 heterocyclo)-, —(C3-C8 heterocyclo)-C1-C10 alkylene-, —(CH2CH2O)r, and —(CH2CH2O)r—CH2—;
• r is an integer ranging from 1-10;
• p ranges from 1 to about 20, and
• D is a drug moiety of Formula DF:
• wherein the wavy line of DF indicates the covalent attachment site to C(O) in formula IIIa, independently at each location:
• R2 is selected from the group consisting of H and C1-C8 alkyl;
• R3 is selected from the group consisting of H, C1-C8 alkyl, C3-C8 carbocycle, aryl, C1-C8 alkyl-aryl, C1-C8 alkyl-(C3-C8 carbocycle), C3-C8 heterocycle and C1-C8 alkyl-(C3-C8 heterocycle);
• R4 is selected from the group consisting of H, C1-C8 alkyl, C3-C8 carbocycle, aryl, C1-C8 alkyl-aryl, C1-C8 alkyl-(C3-C8 carbocycle), C3-C8 heterocycle and C1-C8 alkyl-(C3-C8 heterocycle);
• R5 is selected from the group consisting of H and methyl;
• or R4 and R5 jointly form a carbocyclic ring and have the formula —(CRaRb)n— wherein Ra and Rb are independently selected from the group consisting of H, C1-C8 alkyl and C3-C8 carbocycle and n is selected from the group consisting of 2, 3, 4, 5 and 6;
• R6 is selected from the group consisting of H and C1-C8 alkyl;
• R7 is selected from the group consisting of H, C1-C8 alkyl, C3-C8 carbocycle, aryl, C1-C8 alkyl-aryl, C1-C8 alkyl-(C3-C8 carbocycle), C3-C8 heterocycle and C1-C8 alkyl-(C3-C8 heterocycle);
• each R8 is independently selected from the group consisting of H, OH, C1-C8 alkyl, C3-C8 carbocycle and O—(C1-C8 alkyl);
• R9 is selected from the group consisting of H and C1-C8 alkyl;
• R10 is selected from aryl or C3-C8 heterocycle;
• Z is O, S, NH, or NR12, wherein R12 is C1-C8 alkyl;
• R11 is selected from H, C1-C20 alkyl, aryl, C3-C8 heterocycle, —(R13O)m—R14, or —(R13O)m—CH(R15)2;
• m is an integer ranging from 1-1000;
• R13 is C2-C8 alkyl;
• R14 is H or C1-C8 alkyl;
• each occurrence of R15 is independently H, COOH, —(CH2)n—N(R16)2, —(CH2)n—SO3H, or —(CH2)n—SO3—C1-C8 alkyl;
• each occurrence of R16 is independently H, C1-C8 alkyl, or —(CH2)n—COOH;
• and
• n is an integer ranging from 0 to 6.