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

M Xue; B H Long; C Fairchild; K Johnston; W C Rose; J F Kadow; D M Vyas; S H Chen

doi:10.1016/s0960-894x(00)00242-0

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

Bioorg Med Chem Lett. 2000 Jun 19;10(12):1327-31. doi: 10.1016/s0960-894x(00)00242-0.

Authors

M Xue¹, B H Long, C Fairchild, K Johnston, W C Rose, J F Kadow, D M Vyas, S H Chen

Affiliation

¹ Bristol-Myers Squibb Research Institute, Wallingford, CT 06492-7660, USA.

PMID: 10890157
DOI: 10.1016/s0960-894x(00)00242-0

Abstract

The syntheses and preliminary biological evaluation of 3'-N-thiocarbamate- and 3'-N-thiourea-bearing paclitaxel analogues, 4a-f and 5a-e, are described. 3'-N-thiocarbamates 4a-e were found to be more potent than paclitaxel in both the tubulin polymerization assay and the in vitro cytotoxicity assay. Several derivatives of this class such as 4c, 4d, and 4e also exhibited some in vivo activity.

MeSH terms

Antineoplastic Agents, Phytogenic / chemical synthesis
Antineoplastic Agents, Phytogenic / chemistry*
Antineoplastic Agents, Phytogenic / pharmacology*
Paclitaxel / analogs & derivatives*
Paclitaxel / chemical synthesis
Paclitaxel / chemistry
Paclitaxel / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents, Phytogenic
Paclitaxel