475576-80-8Relevant articles and documents
Discovery of 4-aryl-4H-chromenes as a new series of apoptosis inducers using a cell- and caspase-based high-throughput screening assay. 3. Structure-activity relationships of fused rings at the 7,8-positions
Kemnitzer, William,Drewe, John,Jiang, Songchun,Zhang, Hong,Zhao, Jianghong,Crogan-Grundy, Candace,Xu, Lifen,Lamothe, Serge,Gourdeau, Henriette,Denis, Réal,Tseng, Ben,Kasibhatla, Shailaja,Sui, Xiong Cai
, p. 2858 - 2864 (2007)
As a continuation of our efforts to discover and develop the apoptosis-inducing 4-aryl-4H-chromenes as novel anticancer agents, we explored the SAR of fused rings at the 7,8-positions. It was found that a five-member aromatic ring, such as pyrrolo with nitrogen at either the 7- or 9-position, is preferred. A six-member aromatic ring, such as benzo or pyrido, also led to potent compounds. The SAR of the 4-aryl group was found to be similar for chromenes with a fused ring at the 7,8-positions. These compounds were found to inhibit tubulin polymerization, indicating that cyclization of the 7,8-positions into a ring does not change the mechanism of action. Compound 2h was identified to be a highly potent apoptosis inducer with an EC50 of 5 nM and a highly potent inhibitor of cell proliferation with a GI50 of 8 nM in T47D cells.
