BOURVADIN DERIVATIVES AND THERAPEUTIC USES THEREOF

摘要

The present invention is directed at bouvardin analogs arid related compounds for the treatment of disorders including cancer. Provided herein are bouvardin analogs and related compounds, pharmaceutical compositions and kits comprising at least one bouvardin analog or related compound, and methods for treating disorders including cancer. In some aspects the compounds inhibit translation elongation at the ribosome. The compounds are used in combination with radiation therapy or with known chemotherapeutic compositions.

主权项

1. A compound of Formula I: Wherein: R1, R2, R3, R3a and R3b are independently selected from the group consisting of H, halogen, hydroxyl, C1-8 alkyl, C1-8 haloalkyl, heteroalkyl, C3-8 cycloalkyl, amino, cyano, nitro, aryl, heteroaryl, aminoacyl and acylamino; R4 is selected from the group consisting of H, C1-8 alkyl, C1-8 haloalkyl, C3-8 cycloalkyl, heteroalkyl, aryl and heteroaryl; R5, R6 and R7 are independently selected from the group consisting of H, C1-8 alkyl, C1-8 haloalkyl, heteroalkyl, C3-8 cycloalkyl, alkyl carboxylic acid, alkylaryl, alkylheteroaryl, aryl and heteroaryl; R8, R9, R10, R11, R12 and R13 are independently selected from the group consisting of H, C1-8 alkyl, heteroalkyl, aryl, heteroaryl, C1-8 haloalkyl and C3-8 cycloalkyl; or a pharmaceutically acceptable salt thereof, with the proviso that the compound is not selected from natural products RA-I, RA-II, RA-III, RA-IV, deoxybouvardin(RA-V), RA-VII, RA-VIII, RA-X, RA-XI, RA-XII, RA-XIII and the following: