Identification of novel and improved antimitotic agents derived from noscapine

  • J Med Chem. 2005 Nov 17;48(23):7096-8. doi: 10.1021/jm050674q.
James T Anderson  1 ,  Anthony E Ting ,  Sherry Boozer ,  Kurt R Brunden ,  Chris Crumrine ,  Joel Danzig ,  Tom Dent ,  Laurel Faga ,  John J Harrington ,  William F Hodnick ,  Steven M Murphy ,  Gary Pawlowski ,  Robert Perry ,  Amy Raber ,  Stephen E Rundlett ,  Alain Stricker-Krongrad ,  Jianmin Wang ,  Youssef L Bennani
Affiliations
  • 1. Athersys, Inc., 3201 Carnegie Avenue, Cleveland, Ohio 44115-2634, USA. [email protected]
PMID: 16279766 DOI: 10.1021/jm050674q
Abstract

Analogues of the natural product noscapine were synthesized and their potential as antitumor agents evaluated. The discovery of a novel regioselective O-demethylation facilitated the synthesis of the potent aniline 6, which arrests mammalian cells in the G2/M phase of the cell cycle at 0.1 microM and also affects tubulin polymerization. Aniline 6 is orally bioavailable and is 250-fold more potent than noscapine in reducing cell proliferation in rapidly dividing cells.