NOVEL MAYTANSINOID DERIVATIVES WITH PEPTIDE LINKER AND CONJUGATES THEREOF

摘要

The invention relates to novel cell-binding agent-cytotoxic agent conjugate having a peptide linkers and more specifically to conjugates of formula (I). The invention also provides novel cytotoxic agents of formula (II), linker compounds represented by formula (III), and drug-linker compounds represented by formula (IV). The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

主权项

1. A cell-binding agent-cytotoxic agent conjugate represented by the following structural formula:or a pharmaceutically acceptable salt thereof, wherein:
CB is a cell-binding agent; L2 is is represented by:wherein:
Rx, Ry, Rx′, Ry′, Rx″ and Ry″, for each occurrence, are each independently H, C1-4 alkyl, —OH, halogen or —O—(C1-4 alkyl); R16, for each occurrence, is independently H, an alkyl, halogen, —OH, —O-alkyl, —NO2, or —CN; and l, k and h are each independently an integer from 1 to 10; A is an amino acid or a peptide comprising 2 to 20 amino acids; —Z—X-L1-D is represented by one of the following structural formulas: wherein May is represented by the following structural formula: R1, R2, Ra, Rb and Rc are each independently H or a C1-4 alkyl; and m2, m2′ and n2 are each independently an integer from 1 to 10; and q is an integer from 1 to 20.