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Synthesis and Biological Evaluation of Novel Epothilone B Side Chain Analogues
Author(s) -
Nicolaou K. C.,
Rhoades Derek,
Wang Yanping,
Totokotsopoulos Sotirios,
Bai Ruoli,
Hamel Ernest
Publication year - 2015
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201500401
Subject(s) - epothilones , epothilone , stille reaction , chemistry , ixabepilone , cytotoxicity , combinatorial chemistry , stereochemistry , side chain , iodide , biochemistry , in vitro , biology , organic chemistry , cancer , metastatic breast cancer , polymer , breast cancer , genetics , catalysis
The design, synthesis, and biological evaluation of a series of epothilone analogues with novel side chains equipped with an amino group are described. Their design facilitates potential conjugation to selective drug delivery systems such as antibodies. Their synthesis proceeded efficiently via Stille coupling of a readily available vinyl iodide and heterocyclic stannanes. Cytotoxicity studies and tubulin binding assays revealed two of these analogues to be more potent than epothilones A–D and the anticancer agent ixabepilone, currently in clinical use.