β-glucuronide-linker drug conjugates

1. A drug linker conjugate compound having formula I:

or a pharmaceutically acceptable salt or solvate thereof,

-A- is a Stretcher Unit;

subscript a is 1 or 2

wherein the Stretcher Unit has a functional group that is capable of forming a bond with a functional group of a Ligand Unit;

each —W— is independently a Glucuronide Unit having the structure of

wherein Z is a self-immolative group that forms a first covalent bond with a Self-Immolative Spacer Unit of Y y when subscript y is 1 or 2 or with D when subscript y is 0, and forms a second covalent bond with a Stretcher Unit of A a , wherein the covalent bonds are indicated by the wavy lines to Z,

wherein the Glucuronide Unit structure is represented by

wherein Su is a Sugar moiety;

—O′— represents an oxygen atom of an O-glycosidic bond cleavable by a glycosidase;

each R is independently hydrogen, a halogen, —CN, or NO 2 ;

subscript w is 1 or 2;

—Y— is a Self-Immolative Spacer Unit;

subscript y is 0, 1 or 2; and

-D is a Drug Unit,

wherein the wavy bond to the oxygen atom indicates covalent attachment of that atom to the Self-Immolative Spacer Unit when the subscript y is 1 or 2, or to a Drug unit when the subscript y is 0, and

wherein the wavy bond to the nitrogen atom indicates covalent attachment of that atom to the Stretcher unit.

2. The drug linker conjugate compound of claim 1 wherein subscript w is 1 and the Glucuronide Unit structure is represented by the formula of:

3. The drug linker conjugate compound of claim 1 wherein subscript w is 1 and the drug-linker conjugate compound is one of formula IIa and IIb:

or a pharmaceutically acceptable salt or solvate thereof.

4. The drug linker conjugate compound of claim 3 wherein the drug-linker conjugate compound of formula IIa has the formula:

or a pharmaceutically acceptable salt or solvate thereof.

5. The drug linker conjugate compound of claim 4 wherein the drug-linker conjugate compound has the formula:

or a pharmaceutically acceptable salt or solvate thereof.

6. The drug linker conjugate compound of claim 3 , wherein the Drug Unit is a DNA minor groove binder.

7. The drug linker conjugate compound of claim 3 , wherein the Drug Unit is an alkylating agent.

8. The drug linker conjugate compound of claim 3 , wherein the Drug Unit is an antitubulin agent.

9. The drug linker conjugate compound of claim 3 , wherein the Drug Unit is a maytansinoid.

10. The drug linker conjugate compound of claim 3 , wherein the Drug Unit is an auristatin.

11. The drug linker conjugate compound of claim 10 , wherein D has the formula:

wherein the wavy line adjacent to the nitrogen atom indicates covalent attachment of that atom to a Self-Immolative Spacer Unit of Y y .

12. The drug linker conjugate compound of claim 10 , wherein D has the formula:

wherein the wavy line adjacent to the nitrogen atom indicates covalent attachment of that atom to a Self-Immolative Spacer Unit of Y y .