Synthesis of C2-C3'N-linked macrocyclic taxoids. Novel docetaxel analogues with high tubulin activity

…, S Thoret, F Roussi, F Guéritte, D Guénard

Index: Querolle, Olivier; Dubois, Joelle; Thoret, Sylviane; Roussi, Fanny; Gueritte, Francoise; Guenard, Daniel Journal of Medicinal Chemistry, 2004 , vol. 47, # 24 p. 5937 - 5944

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Citation Number: 34

Abstract

Novel C2-C3'N-linked macrocyclic taxoids 4 bearing an aromatic ring at position C2 were synthesized. These compounds, tethered between N3'and the C2-aromatic ring at the ortho, meta, or para position, were constructed by ring-closing metathesis. The para-substituted derivatives were unable to stabilize microtubules, whereas the ortho-and meta-substituted compounds show significant activity in cold-induced microtubule disassembly assay. The ...