1,4,5,6-Tetrahydropyrrolo[3,4-c]pyrazoles: Identification of a potent aurora kinase inhibitor with a favorable antitumor kinase inhibition profile

Daniele Fancelli, 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 SeverinoChiara Soncini, Paola Storici, Roberto Tonani, Paola Zugnoni, Paola Vianello

Research output: Contribution to journalArticle

136 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7247-7251
Number of pages5
JournalJournal of Medicinal Chemistry
Volume49
Issue number24
DOIs
Publication statusPublished - Nov 30 2006

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Aurora Kinases
Pyrazoles
Phosphotransferases
Pharmacokinetics
Tumors
Neoplasms
Cells
Derivatives
Cell Line

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

1,4,5,6-Tetrahydropyrrolo[3,4-c]pyrazoles : Identification of a potent aurora kinase inhibitor with a favorable antitumor kinase inhibition profile. / Fancelli, Daniele; Moll, Jürgen; Varasi, Mario; Bravo, Rodrigo; Artico, Roberta; Berta, Daniela; Bindi, Simona; Cameron, Alexander; Candiani, Ilaria; Cappella, Paolo; Carpinelli, Patrizia; Croci, Walter; Forte, Barbara; Giorgini, Maria Laura; Klapwijk, Jan; Marsiglio, Aurelio; Pesenti, Enrico; Rocchetti, Maurizio; Roletto, Fulvia; Severino, Dino; Soncini, Chiara; Storici, Paola; Tonani, Roberto; Zugnoni, Paola; Vianello, Paola.

In: Journal of Medicinal Chemistry, Vol. 49, No. 24, 30.11.2006, p. 7247-7251.

Research output: Contribution to journalArticle

Fancelli, D, Moll, J, Varasi, M, Bravo, R, Artico, R, Berta, D, Bindi, S, Cameron, A, Candiani, I, Cappella, P, Carpinelli, P, Croci, W, Forte, B, Giorgini, ML, Klapwijk, J, Marsiglio, A, Pesenti, E, Rocchetti, M, Roletto, F, Severino, D, Soncini, C, Storici, P, Tonani, R, Zugnoni, P & Vianello, P 2006, '1,4,5,6-Tetrahydropyrrolo[3,4-c]pyrazoles: Identification of a potent aurora kinase inhibitor with a favorable antitumor kinase inhibition profile', Journal of Medicinal Chemistry, vol. 49, no. 24, pp. 7247-7251. https://doi.org/10.1021/jm060897w
Fancelli, Daniele ; Moll, Jürgen ; Varasi, Mario ; Bravo, Rodrigo ; Artico, Roberta ; Berta, Daniela ; Bindi, Simona ; Cameron, Alexander ; Candiani, Ilaria ; Cappella, Paolo ; Carpinelli, Patrizia ; Croci, Walter ; Forte, Barbara ; Giorgini, Maria Laura ; Klapwijk, Jan ; Marsiglio, Aurelio ; Pesenti, Enrico ; Rocchetti, Maurizio ; Roletto, Fulvia ; Severino, Dino ; Soncini, Chiara ; Storici, Paola ; Tonani, Roberto ; Zugnoni, Paola ; Vianello, Paola. / 1,4,5,6-Tetrahydropyrrolo[3,4-c]pyrazoles : Identification of a potent aurora kinase inhibitor with a favorable antitumor kinase inhibition profile. In: Journal of Medicinal Chemistry. 2006 ; Vol. 49, No. 24. pp. 7247-7251.
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