Synapse - Complex target-oriented total synthesis in the drug discovery process: The discovery of a highly promising family of second generation epothilones

Complex target-oriented total synthesis in the drug discovery process: The discovery of a highly promising family of second generation epothilones Journal Article

Authors:	Rivkin, A.; Yoshimura, F.; Gabarda, A. E.; Chou, T. C.; Dong, H.; Tong, W. P.; Danishefsky, S. J.
Article Title:	Complex target-oriented total synthesis in the drug discovery process: The discovery of a highly promising family of second generation epothilones
Abstract:	The total synthesis of a family of (E)-9,10-dehydro derivatives of epothilone D (i.e., 12,13-desoxyepothilone B) is described. The route is particularly concise and amenable to production of new congeners. Furthermore, the chemistry described herein constitutes a major simplification in the total synthesis of EpoD, which is in human clinical trials. This new family of epothilones shows major advantages in terms of their potency and pharmacostability relative to the wild-type saturated analogues in the D series. From the perspective of compound availability through synthesis, potency, and pharmacokinetic properties, these compounds could well warrant advancement to clinical evaluation in humans. Copyright © 2003 American Chemical Society.
Keywords:	controlled study; unclassified drug; human cell; nonhuman; antineoplastic agents; paclitaxel; antineoplastic agent; mouse; cell division; animal model; hct116 cells; antineoplastic activity; cytotoxicity; drug potency; drug structure; drug screening assays, antitumor; drug design; drug synthesis; structure-activity relationship; vinblastine; nude mouse; tumor cell line; drug cytotoxicity; tumor growth; plasma; drug stability; epothilones; epothilone derivative; growth inhibition; 12,13 desoxyepothilone b; humans; human; article; 9,10 dehydro 12,13 desoxyepothilone b
Journal Title:	Journal of the American Chemical Society
Volume:	125
Issue:	10
ISSN:	0002-7863
Publisher:	American Chemical Society
Date Published:	2003-03-12
Start Page:	2899
End Page:	2901
Language:	English
DOI:	10.1021/ja029695p
PUBMED:	12617656
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-0037433593&partnerID=40&md5=e8a6a914d665f92562f33a1b7fd9b0aa
Notes:	Export Date: 12 September 2014 -- Source: Scopus

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MSK Authors

10 Rivkin
158 Tong
7 Yoshimura
7 Gabarda Ortega
33 Dong
539 Danishefsky
318 Chou

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