Synthesis of Epothilone Analogs: Toward the Development of Potent Anticancer Drugs

Download or read book Synthesis of Epothilone Analogs: Toward the Development of Potent Anticancer Drugs written by and published by . This book was released on 2002 with total page 67 pages. Available in PDF, EPUB and Kindle. Book excerpt: Epothilones are cytotoxic natural products that inhibit the growth of cancer cells by the same tubulin-stabilizing mechanism of Taxol. We have been developing a program in epothilone-based chemotherapy, and have succeeded in accomplishing efficient synthetic protocols to access large amounts of important analogs quickly. Our lead candidate, l2,l3-desoxyepothilone B (dEpoB), is currently in Phase I clinical trials. To further develop and screen a variety of strong back-up candidates in our clinical development program, we have made and tested a series of dehydro-desoxy-epothilones. In the process, we have also discovered an even more practical synthetic process toward the synthesis of our lead drug candidate, dEpoB. We have also examined the scope of synthetic modifications to the natural epothilone structure with regards to biological activity. These experiments include the expansion of the ring-size of the epothilones and introduction of trifluoromethyl groups. These studies demonstrate that the dehydroepothilones are viable cytotoxic agents, and that minimal ring-expansion strategies maintain the biological activity of the epothilones.