title: Design and synthesis of simplified taxol analogs based on the T-Taxol bioactive conformation.
abstract: A series of compounds designed to adopt a conformation similar to the tubulin-binding T-Taxol conformation of the anticancer drug paclitaxel has been synthesized. Both the internally bridged analogs 37-39, 41 and the open-chain analogs 27-29 and 43 were prepared. The bridged analogs 37-39 and 41 were synthesized by Grubbs' metatheses of compounds 30-32 and 33, which, in turn, were prepared by coupling β-lactams 24-26 with alcohols 22 and 23. Both the bridged and the open-chain analogs showed moderate to good cytotoxicity.
authors.affiliation: Department of Chemistry, Virginia Tech, Blacksburg, VA 24061, USA.
authors.forename: Jielu
authors.initials: J
authors.lastname: Zhao
authors.forename: Susan
authors.initials: S
authors.lastname: Bane
authors.forename: James P
authors.initials: JP
authors.lastname: Snyder
authors.forename: Haipeng
authors.initials: H
authors.lastname: Hu
authors.forename: Kamalika
authors.initials: K
authors.lastname: Mukherjee
authors.forename: Carla
authors.initials: C
authors.lastname: Slebodnick
authors.forename: David G I
authors.initials: DG
authors.lastname: Kingston
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D017239:Paclitaxel
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