1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile

  • J Med Chem. 2006 Nov 30;49(24):7247-51. doi: 10.1021/jm060897w.
Daniele Fancelli  1 ,  Jürgen Moll ,  Mario Varasi ,  Rodrigo Bravo ,  Roberta Artico ,  Daniela Berta ,  Simona Bindi ,  Alexander Cameron ,  Ilaria Candiani ,  Paolo Cappella ,  Patrizia Carpinelli ,  Walter Croci ,  Barbara Forte ,  Maria Laura Giorgini ,  Jan Klapwijk ,  Aurelio Marsiglio ,  Enrico Pesenti ,  Maurizio Rocchetti ,  Fulvia Roletto ,  Dino Severino ,  Chiara Soncini ,  Paola Storici ,  Roberto Tonani ,  Paola Zugnoni ,  Paola Vianello
Affiliations
  • 1. Nerviano Medical Sciences S.r.l. viale Pasteur 10, 20014 Nerviano, Milan, Italy.
PMID: 17125279 DOI: 10.1021/jm060897w
Abstract

The optimization of a series of 5-phenylacetyl 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives toward the inhibition of Aurora Kinases led to the identification of compound 9d. This is a potent inhibitor of Aurora Kinases that also shows low nanomolar potency against additional Anticancer kinase targets. Based on its high antiproliferative activity on different Cancer cell lines, favorable chemico-physical and pharmacokinetic properties, and high efficacy in in vivo tumor models, compound 9d was ultimately selected for further development.