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

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

  • Bioorg Med Chem Lett. 2011 Mar 15;21(6):1634-8. doi: 10.1016/j.bmcl.2011.01.097.
Sridhar Narayan 1,  Eric M Carlson,  Hongsheng Cheng,  Krista Condon,  Hong Du,  Sean Eckley,  Yongbo Hu,  Yimin Jiang,  Vipul Kumar,  Bryan M Lewis,  Philip Saxton,  Edgar Schuck,  Boris M Seletsky,  Karen Tendyke,  Huiming Zhang,  Wanjun Zheng,  Bruce A Littlefield,  Murray J Towle,  Melvin J Yu
Affiliations

Affiliation

  • 1 Eisai Product Creation Systems, Eisai Inc., Andover, MA 01810, USA. [email protected]
PMID: 21324692 DOI: 10.1016/j.bmcl.2011.01.097
Abstract

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.

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