Methylene Carbamate Linkers for use with Targeted-Drug Conjugates

A Drug-Linker compound, wherein the compound comprises a Drug Unit and a Linker Unit, wherein the Linker Unit comprises a Self-Immolative Assembly Unit having a methylene carbamate unit and an activateable self-immolative moiety wherein the Drug Unit is covalently attached to the methylene carbamate unit,

• wherein the Drug-Linker compound has the structure of formula V:
• or a pharmaceutically acceptable salt thereof;
• wherein
• D is a Drug Unit incorporating a free drug having a hydroxyl, thiol, amine or amide functional group, wherein the functional group has been incorporated into the indicated methylene carbamate unit;
• T* is the oxygen, sulfur or optionally substituted nitrogen heteroatom from said functional group;
• R, R1 and R2 independently are hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C6-14 aryl, or optionally substituted C-linked heteroaryl having from 3 to 8 carbon atom ring members and one to four heteroatom ring members independently selected from the group consisting of N, O, P and S, or
• wherein R is a Basic Unit wherein the basic functional group of the Basic Unit is an amine or a nitrogen-containing 3, 4, 5, or 6 membered heterocycle, optionally substituted, wherein the heterocycle is C-linked or N-linked, or the basic functional group of the Basic Unit is —N(Rop)2, wherein each Rop is independently selected from the group consisting of hydrogen and C1-C6 alkyl or each Rop is methyl;
• X is an activateable self-immolative moiety;
• Z′ is a Stretcher Unit precursor to a Stretcher Unit (Z) and comprises a functional group that provides for covalent attachment of a Ligand Unit to Z;
• B is an optional Branching Unit that is present when t is greater than 1 and is absent when tis 1;
• A is an optional Connector Unit;
• and
• the subscript t ranges from 1 to 4.