Structure-activity relationships study at the 3 '-N position of paclitaxel. Part 2: Synthesis and biological evaluation of 3 '-N-thiourea- and 3 '-N-thiocarbamate-bearing paclitaxel analogues

The syntheses and preliminary biological evaluation of 3'-N-thiocarbamate- and 3'-N'-thiourea-bearing paclitaxel analogues, 4a-f and 5a-e, are describ ed. 3'-N-thiocarbamates 4a-e were found to be more potent than paclitaxel i n both the tubulin polymerization assay and the in vitro cytotoxicity assay . Several derivatives of this class such as 4c, 4d, and 4e also exhibited s ome in vivo activity. (C) 2000 Elsevier Science Ltd. All rights reserved.