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 Severino; Chiara Soncini; Paola Storici; Roberto Tonani; Paola Zugnoni; Paola Vianello

doi:10.1021/jm060897w

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

Istituto Europeo di Oncologia

Research output: Contribution to journal › Article › peer-review

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 language	English
Pages (from-to)	7247-7251
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	49
Issue number	24
DOIs	https://doi.org/10.1021/jm060897w
Publication status	Published - Nov 30 2006

ASJC Scopus subject areas

Organic Chemistry

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10.1021/jm060897w

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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, M. L., Klapwijk, J., Marsiglio, A., Pesenti, E., Rocchetti, M., Roletto, F., ... 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, 49(24), 7247-7251. https://doi.org/10.1021/jm060897w

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 journal › Article › peer-review

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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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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AU - Artico, Roberta

AU - Berta, Daniela

AU - Bindi, Simona

AU - Cameron, Alexander

AU - Candiani, Ilaria

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AU - Carpinelli, Patrizia

AU - Croci, Walter

AU - Forte, Barbara

AU - Giorgini, Maria Laura

AU - Klapwijk, Jan

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AU - Pesenti, Enrico

AU - Rocchetti, Maurizio

AU - Roletto, Fulvia

AU - Severino, Dino

AU - Soncini, Chiara

AU - Storici, Paola

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AU - Zugnoni, Paola

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

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