Monomethylvaline compounds capable of conjugation to ligands

A method for treating cancer comprising administering to a patient in need thereof an effective amount of an antibody-drug conjugate having Formula Ia′:

• AbAa-Ww-Yy-D)p Ia′
• or a pharmaceutically acceptable salt thereof, wherein:
• Ab is an antibody that specifically binds to an antigen expressed by the cancer,
• A is a Stretcher unit,
• a is 1,
• each W is independently an Amino Acid unit,
• w is an integer ranging from 2 to 12,
• Y is a Spacer unit, and
• y is 1 or 2,
• 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 Y:
• R2 is selected from H and C1-C8 alkyl;
• R3 is selected from 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 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 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 H, C1-C8 alkyl and C3-C8 carbocycle and n is selected from 2, 3, 4, 5 and 6;
• R6 is selected from H and C1-C8 alkyl;
• R7 is selected from 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 H, OH, C1-C8 alkyl, C3-C8 carbocycle and O—(C1-C8 alkyl);
• R9 is selected from 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-C88 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.