NOVEL MAYTANSINOID DERIVATIVES WITH SULFOXIDE LINKER

摘要

The invention relates to novel maytansinoid compounds having sulfoxide linkers and more specifically to novel maytansinoid compounds of structural formula (I) and (II). The invention also provides conjugates of the maytansinoid compounds linked to a cell-binding agent. 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 compound represented by the following structural formula: wherein:
D is a cytotoxic agent;X is S or Se;R and R′ are each independently selected from the group consisting of —H, an alkyl, a cycloalkyl, —ORa, and —NRbRc;Ra, Rb and Rc are each independently H or an alkyl;p is 0, 1 or 2Y is an alkylene, a polyethylene glycol unit represented by —(CH2—CH2—O)n—Rd—, —Rd-E- or —Rd—W—Re—,n is an integer from 1 to 24;E is a cycloalkyl, a heterocyclyl, an aryl or a heteroaryl,W is —C(═O)NH—, —NHC(═O)—, —(C═O)O— or —O(C═O)—,Rd is absent or an alkyl;Re is an alkyl;M is a linking group that can react with a cell-binding agent to form a covalent bond.