2. Academic Validation
  3. Pyrazole diaminopyrimidines as dual inhibitors of KDR and Aurora B kinases

Pyrazole diaminopyrimidines as dual inhibitors of KDR and Aurora B kinases

  • Bioorg Med Chem Lett. 2012 Jul 15;22(14):4750-5. doi: 10.1016/j.bmcl.2012.05.067.
Michael L Curtin 1,  H Robin Heyman,  Robin R Frey,  Patrick A Marcotte,  Keith B Glaser,  James R Jankowski,  Terrance J Magoc,  Daniel H Albert,  Amanda M Olson,  David R Reuter,  Jennifer J Bouska,  Debra A Montgomery,  Joann P Palma,  Cherrie K Donawho,  Kent D Stewart,  Chris Tse,  Michael R Michaelides
Affiliations

Affiliation

  • 1 Global Pharmaceutical Research and Development, Abbott Laboratories, 100 Abbott Park Road, Abbott Park, IL 60064-6100, USA. mike.curtin@abbott.com
PMID: 22695126 DOI: 10.1016/j.bmcl.2012.05.067
Abstract

In an effort to identify kinase inhibitors with dual KDR/Aurora B activity and improved aqueous solubility compared to the Abbott dual inhibitor ABT-348, a series of novel pyrazole pyrimidines structurally related to kinase inhibitor AS703569 were prepared. SAR work provided analogs with significant cellular activity, measureable aqueous solubility and moderate antitumor activity in a mouse tumor model after weekly IP dosing. Unfortunately these compounds were pan-kinase inhibitors that suffered from narrow therapeutic indices which prohibited their use as antitumor agents.

Figures