Synthesis and biological evaluation of highly potent analogues of epothilones B and D

• Published in: Bioorganic & medicinal chemistry letters Vol. 10; no. 24; pp. 2765 - 2768
• Main Authors: Altmann, Karl-Heinz, Bold, Guido, Caravatti, Giorgio, Flörsheimer, Andreas, Guagnano, Vito, Wartmann, Markus
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 18.12.2000; Elsevier
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Division - drug effects; Drug Resistance; Epothilones; Epoxy Compounds - chemical synthesis; Epoxy Compounds - pharmacology; General aspects; Humans; Inhibitory Concentration 50; Medical sciences; Paclitaxel; Pharmacology. Drug treatments; Stereoisomerism; Thiazoles - chemical synthesis; Thiazoles - pharmacology; Tumor Cells, Cultured; Antineoplastic agent; Cell proliferation; Sulfur nitrogen heterocycle; Nitrogen heterocycle; Ketol; Lactone; Benzothiazole derivatives; Oxygen heterocycle; In vitro; Macrolide; Biological activity; Macrocycle; Side chain; Cell line; Benzimidazole derivatives; Epoxide; Inhibition; Chemical synthesis; Tumor cell
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(00)00555-2

A series of new epothilone B and D analogues incorporating fused hetero-aromatic side chains have been prepared. The synthetic strategy is based on olefin 3 as the common intermediate and allows variation of the side-chain structure in a highly convergent and stereoselective manner. Epothilone analogues 1a– d and 2a– d are more potent inhibitors of cancer cell proliferation than the corresponding parent epothilones B or D.