Paclitaxel enhancer compounds

摘要

Disclosed is a compound represented by the Structural Formula (I):;Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group. In addition, Y, taken together with both >C═Z groups to which it is bonded, is a substituted or unsubstituted aromatic group. Preferably, Y is a covalent bond or —C(R7R8)—.R1 and R2 are independently an aryl group or a substituted aryl group, R3 and R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group.R5-R6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group.R7 and R8 are each independently —H, an aliphatic or substituted aliphatic group, or R7 is —H and R8 is a substituted or unsubstituted aryl group, or, R7 and R8, taken together, are a C2-C6 substituted or unsubstituted alkylene group.Z is ═O or ═S.;Also disclosed are pharmaceutical compositions comprising the compound of the present invention and a pharmaceutically acceptable carrier or diluent.;Also disclosed is a method of treating a subject with cancer by administering to the subject a compound of Structural Formula (I) in combination with Paclitaxel or an analog of Paclitaxel.

主权项

1. A method of treating a subject with a cancer comprising administering to the subject an effective amount of paclitaxel or a paclitaxel analog and an effective amount of a compound represented by the following structural formula: or a pharmaceutically acceptable salt thereof, wherein:
Y is a covalent bond, a phenylene group or a substituted or unsubstituted straight chained hydrocarbyl group, or, Y, taken together with both >C═Z groups to which it is bonded, is a substituted or unsubstituted aromatic group;R1 and R2 are independently an aryl group or a substituted aryl group;R3 and R4 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group;R5-R6 are independently —H, an aliphatic group, a substituted aliphatic group, an aryl group or a substituted aryl group; andZ is ═O or ═S;provided that when Y is —CH2—, R3 and R4 are both phenyl and R5—R6 are all —H, then R1 and R2 are not both phenyl;and wherein the cancer is selected from the group consisting of colon cancer, pancreatic cancer, renal cancer, sarcoma, breast cancer, ovarian cancer, stomach cancer, bladder cancer and cervical cancer.