Structure-activity relationships in side-chain-modified epothilone analogues - How important is the position of the nitrogen atom?

被引：20

作者：

Bold, Guido

Wojeik, Severine

Caravatti, Giorgio

Lindauer, Renate

Stierlin, Claire

Gertsch, Juerg

Wartmann, Markus

Altmann, Karl-Heinz

机构：

[1] ETH Zürich, Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, 8093 Zürich

[2] Global Discovery Chemistry, Novartis Institute for Biomedical Research, Basel

[3] Oncology DA, Novartis Institute for Biomedical Research, Basel

来源：

CHEMMEDCHEM | 2006年 / 1卷 / 01期

关键词：

Antitumor agents; Epothilones; Natural products; Structure-activity relationships; Total synthesis;

D O I：

10.1002/cmdc.200500051

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Side-chain-modified epothilone analogues 1 b, 2 b, and 3 b were prepared through stereoselective total synthesis to assess the importance of N-atom positioning in the side chain for tubulin polymerization and anti proliferative activity. Surprisingly, 1 b, 2b, and 3b appear to induce tubulin polymerization with activities similar to those of 1 a, 2a, and 3a, respectively. Substantial differences in antiproliferative activity were observed between 1 a and 2 a, and 1 b and 2b, but not between 3 a and 3b.

引用

页码：37 / 40

页数：4

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