COMPOSITIONS AND METHODS FOR CANCER THERAPY

摘要

The invention provides compositions and methods to treat cancer with an agent that selectively promotes cancer cell death relative to non-malignant cells by mechanisms that include increased oxidative stress (“a therapeutic agent”) or a pharmaceutically acceptable salt thereof, an inhibitor of hydroperoxide metabolism and a pharmaceutically acceptable diluent or carrier.

主权项

1. A pharmaceutical composition comprising a compound of formula I:
Ph3P+-L-W Y−  Iwherein:
W is selected from: L is absent, (C1-C12)alkyl, (C1-C12)alkylene, —(CH2CH2O)nM-, —C(═O)NRL1- or —NRL1C(═S)NRL1—; n is 1 to 12; M is absent or —CH2CH2—; RL1 is H or (C1-C6)alkyl; R1 is halo or —NHC(═O)Ra; R2 is halo, SRb or —C(═O)NHRc; R3 is —NH(C═O)Rd, —NH(C═O)NHRd or phenyl wherein any phenyl of R3 is optionally substituted with one or more halo, (C1-C3)alkyl, (C1-C3)haloalkyl or —O(C1-C3)alkyl; R4 is (C1-C6)alkyl or phenyl wherein any phenyl of R4 is optionally substituted with one or more halo, (C1-C3)alkyl, (C1-C3)haloalkyl or —O(C1-C3)alkyl; R5 is —S(C1-C6)alkyl or —N((C1-C6)alkyl)2; Ra is phenyl optionally substituted with one or more halo, (C1-C3)alkyl, (C1-C3)haloalkyl or —O(C1-C3)alkyl; Rb is phenyl optionally substituted with one or more halo, (C1-C3)alkyl, (C1-C3)haloalkyl or —O(C1-C3)alkyl; Rc is phenyl optionally substituted with one or more halo, (C1-C3)alkyl, (C1-C3)haloalkyl or —O(C1-C3)alkyl; Rd is independently phenyl optionally substituted with one or more halo, (C1-C3)alkyl, (C1-C3)haloalkyl or —O(C1-C3)alkyl; and Y is a counterion; or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent or carrier.