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

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

Affiliation

  • 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.

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