Hydrophilic self-immolative linkers and conjugates thereof

摘要

The present disclosure provides compounds with a hydrophilic self-immolative linker, which is cleavable under appropriate conditions and incorporates a hydrophilic group to provide better solubility of the compound. The compounds of the present disclosure comprise a drug moiety, a targeting moiety capable of targeting a selected cell population, and a linker which contains an acyl unit, an optional spacer unit for providing distance between the drug moiety and the targeting moiety, a peptide linker which can be cleavable under appropriate conditions, a hydrophilic self-immolative linker, and an optional second self-immolative spacer or cyclization self-elimination linker.

主权项

1. A compound of the formula (II): or a salt or solvate or stereoisomer thereof; wherein: D is a drug moiety; T is a targeting moiety; R1 is hydrogen, unsubstituted or substituted C1-3 alkyl, or unsubstituted or substituted heterocyclyl; L1 is a bond, a second self-immolative linker, or a cyclization self-elimination linker; L2 is a bond or a second self-immolative linker;
wherein if L1 is a second self-immolative linker or a cyclization self-elimination linker, then L2 is a bond;wherein if L2 is a second self-immolative linker, then L1 is a bond; L3 is a peptide linker; L4 is bond or a spacer; and A is an acyl unit.