Design and synthesis of simplified taxol analogs based on the T-Taxol bioactive conformation

Bioorganic & Medicinal Chemistry
2011.0

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.

Knowledge Graph

Similar Paper

Design and synthesis of simplified taxol analogs based on the T-Taxol bioactive conformation
Bioorganic & Medicinal Chemistry 2011.0
Synthesis and bioactivity of a side chain bridged paclitaxel: A test of the T-Taxol conformation
Bioorganic & Medicinal Chemistry Letters 2009.0
Synthesis of C2−C3‘N-Linked Macrocyclic Taxoids. Novel Docetaxel Analogues with High Tubulin Activity
Journal of Medicinal Chemistry 2004.0
Evaluation of the Tubulin-Bound Paclitaxel Conformation:  Synthesis, Biology, and SAR Studies of C-4 to C-3‘ Bridged Paclitaxel Analogues
Journal of Medicinal Chemistry 2007.0
Biologically active taxol analogs with deleted A-ring side chain substituents and variable C-2' configurations
Journal of Medicinal Chemistry 1991.0
Synthesis and NMR-Driven Conformational Analysis of Taxol Analogues Conformationally Constrained on the C13 Side Chain
Journal of Medicinal Chemistry 2001.0
Design and synthesis of de novo cytotoxic alkaloids by mimicking the bioactive conformation of paclitaxel
Bioorganic & Medicinal Chemistry 2010.0
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
Bioorganic & Medicinal Chemistry Letters 2000.0
Structure-activity relationships of taxol®: synthesis and biological evaluation of C2 taxol analogs
Bioorganic & Medicinal Chemistry Letters 1994.0
Butitaxel Analogues:  Synthesis and Structure−Activity Relationships
Journal of Medicinal Chemistry 1997.0