Details

Autor(en) / Beteiligte

• Narayan, Sridhar
• Carlson, Eric M.
• Cheng, Hongsheng
• Condon, Krista
• Du, Hong
• Eckley, Sean
• Hu, Yongbo
• Jiang, Yimin
• Kumar, Vipul
• Lewis, Bryan M.
• Saxton, Philip
• Schuck, Edgar
• Seletsky, Boris M.
• Tendyke, Karen
• Zhang, Huiming
• Zheng, Wanjun
• Littlefield, Bruce A.
• Towle, Murray J.
• Yu, Melvin J.

Titel

Novel second generation analogs of eribulin. Part II: Orally available and active against resistant tumors in vivo

Ist Teil von

• Bioorganic & medicinal chemistry letters, 2011-03, Vol.21 (6), p.1634-1638

Ort / Verlag

Amsterdam: Elsevier Ltd

Erscheinungsjahr

2011

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Eribulin mesylate is a newly approved treatment for locally advanced and metastatic breast cancer. We targeted oral bioavailability and efficacy against multidrug resistant (MDR) tumors for further work. The design, synthesis and evaluation of novel amine-containing analogs of eribulin mesylate are described in this part. Attenuation of basicity of the amino group(s) in the C32 side-chain region led to compounds with low susceptibility to PgP-mediated drug efflux. These compounds were active against MDR tumor cell lines in vitro and in xenograft models in vivo, in addition to being orally bioavailable.