Macrocyclic ketone analogues of halichondrin B

Wanjun Zheng; Boris M Seletsky; Monica H Palme; Paul J Lydon; Lori A Singer; Charles E Chase; Charles A Lemelin; Yongchun Shen; Heather Davis; Lynda Tremblay; Murray J Towle; Kathleen A Salvato; Bruce F Wels; Kimberley K Aalfs; Yoshito Kishi; Bruce A Littlefield; Melvin J Yu

doi:10.1016/j.bmcl.2004.08.069

Macrocyclic ketone analogues of halichondrin B

Bioorg Med Chem Lett. 2004 Nov 15;14(22):5551-4. doi: 10.1016/j.bmcl.2004.08.069.

Authors

Wanjun Zheng¹, Boris M Seletsky, Monica H Palme, Paul J Lydon, Lori A Singer, Charles E Chase, Charles A Lemelin, Yongchun Shen, Heather Davis, Lynda Tremblay, Murray J Towle, Kathleen A Salvato, Bruce F Wels, Kimberley K Aalfs, Yoshito Kishi, Bruce A Littlefield, Melvin J Yu

Affiliation

¹ Department of Medicinal Chemistry, Eisai Research Institute, 4 Corporate Drive, Andover, MA 01810, USA.

PMID: 15482922
DOI: 10.1016/j.bmcl.2004.08.069

Abstract

Structurally simplified macrocyclic ketone analogues of halichondrin B were prepared by total synthesis and found to retain the potent cell growth inhibitory activity in vitro, stability in mouse serum, and in vivo efficacy of the natural product.

MeSH terms

Animals
Cell Division / drug effects
Cell Line, Tumor
Drug Screening Assays, Antitumor
Ethers, Cyclic / chemical synthesis
Ethers, Cyclic / chemistry*
Ethers, Cyclic / pharmacology*
Furans / chemical synthesis
Furans / chemistry
Furans / pharmacology
Humans
Ketones / chemical synthesis
Ketones / chemistry*
Ketones / pharmacology*
Macrocyclic Compounds / chemical synthesis
Macrocyclic Compounds / chemistry*
Macrocyclic Compounds / pharmacology*
Macrolides
Mice
Molecular Conformation
Structure-Activity Relationship

Substances

Ethers, Cyclic
Furans
Ketones
Macrocyclic Compounds
Macrolides
halichondrin B
eribulin