Synthesis and biological evaluation of highly potent analogues of epothilones B and D.
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.
Altmann
K H
KH
Novartis Pharma AG, TA Oncology Research, Basel, Switzerland. karl-heinz.altmann@pharma.novartis.com
Bold
G
G
Caravatti
G
G
Flörsheimer
A
A
Guagnano
V
V
Wartmann
M
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004351:Drug Resistance; D034261:Epothilones; D004852:Epoxy Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D017239:Paclitaxel; D013237:Stereoisomerism; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D034261:Epothilones; D004852:Epoxy Compounds; D013844:Thiazoles; D017239:Paclitaxel; C114026:desoxyepothilone B; C093788:epothilone B