Total Synthesis of an Epothilone Analogue Based on the Amide‐Triazole Bioisosterism

Epothilones are 16‐membered macrolides that act as microtubule‐targeting agents to tackle cancer. Many synthetic analogues have been investigated for their activity, yet often based on macrolide structures. A notable exception is Ixabepilone, an azalide whose metabolic stability and pharmacokinetics...

Full description

Saved in:
Bibliographic Details
Published in:ChemPlusChem (Weinheim, Germany) Germany), 2024-10, Vol.89 (10), p.e202400413-n/a
Main Authors: Colombo, Eleonora, Coppini, Davide A., Borsoi, Simone, Fasano, Valerio, Bucci, Raffaella, Bonato, Francesca, Bonandi, Elisa, Vasile, Francesca, Pieraccini, Stefano, Passarella, Daniele
Format: Article
Language:English
Subjects:
Amides - chemical synthesis
Amides - chemistry
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Epothilone
Epothilones - chemical synthesis
Epothilones - chemistry
Humans
Ixabepilone
Macrolide
Molecular Structure
Triazole
Triazoles - chemical synthesis
Triazoles - chemistry
Tubulin
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Epothilones are 16‐membered macrolides that act as microtubule‐targeting agents to tackle cancer. Many synthetic analogues have been investigated for their activity, yet often based on macrolide structures. A notable exception is Ixabepilone, an azalide whose metabolic stability and pharmacokinetics are significantly improved. Exploiting the amide‐triazole bioisosterism, in this work we report the synthesis of the first generation of epothilones lacking the macrolide or azalide structure, with the ester or amide linkage replaced by a triazole unit. Together with the synthesis of this new analogue, computational and biological evaluations have been performed too. Epotriazole: Exploiting the amide‐triazole bioisosterism, in this work we report the synthesis of the first generation of epothilones lacking the macrolide or azalide structure, with the ester or amide linkage replaced by a triazole unit.
ISSN:2192-6506
2192-6506
DOI:10.1002/cplu.202400413