Thieno[3,2-c]pyrazoles

A novel class of Aurora inhibitors with favorable antitumor activity

Simona Bindi, Daniele Fancelli, Cristina Alli, Daniela Berta, Jay A. Bertrand, Alexander D. Cameron, Paolo Cappella, Patrizia Carpinelli, Giovanni Cervi, Valter Croci, Matteo D'Anello, Barbara Forte, M. Laura Giorgini, Aurelio Marsiglio, Juergen Moll, Enrico Pesenti, Valeria Pittalà, Maurizio Pulici, Federico Riccardi-Sirtori, Fulvia Roletto & 6 others Chiara Soncini, Paola Storici, Mario Varasi, Daniele Volpi, Paola Zugnoni, Paola Vianello

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

A novel series of 3-amino-1H-thieno[3,2-c]pyrazole derivatives demonstrating high potency in inhibiting Aurora kinases was developed. Here we describe the synthesis and a preliminary structure-activity relationship, which led to the discovery of a representative compound (38), which showed low nanomolar inhibitory activity in the anti-proliferation assay and was able to block the cell cycle in HCT-116 cell line. This compound demonstrated favorable pharmacokinetic properties and good efficacy in the HL-60 xenograft tumor model.

Original languageEnglish
Pages (from-to)7113-7120
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number19
DOIs
Publication statusPublished - Oct 1 2010

Fingerprint

Aurora Kinases
Pyrazoles
HCT116 Cells
Structure-Activity Relationship
Heterografts
Cell Cycle
Pharmacokinetics
Cells
Cell Line
Tumors
Assays
Neoplasms
Derivatives
pyrazole

Keywords

  • Anti-cancer
  • Aurora kinases
  • Kinase inhibitor
  • Tumor cell proliferation inhibition

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Organic Chemistry
  • Molecular Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Biochemistry

Cite this

Bindi, S., Fancelli, D., Alli, C., Berta, D., Bertrand, J. A., Cameron, A. D., ... Vianello, P. (2010). Thieno[3,2-c]pyrazoles: A novel class of Aurora inhibitors with favorable antitumor activity. Bioorganic and Medicinal Chemistry, 18(19), 7113-7120. https://doi.org/10.1016/j.bmc.2010.07.048

Thieno[3,2-c]pyrazoles : A novel class of Aurora inhibitors with favorable antitumor activity. / Bindi, Simona; Fancelli, Daniele; Alli, Cristina; Berta, Daniela; Bertrand, Jay A.; Cameron, Alexander D.; Cappella, Paolo; Carpinelli, Patrizia; Cervi, Giovanni; Croci, Valter; D'Anello, Matteo; Forte, Barbara; Laura Giorgini, M.; Marsiglio, Aurelio; Moll, Juergen; Pesenti, Enrico; Pittalà, Valeria; Pulici, Maurizio; Riccardi-Sirtori, Federico; Roletto, Fulvia; Soncini, Chiara; Storici, Paola; Varasi, Mario; Volpi, Daniele; Zugnoni, Paola; Vianello, Paola.

In: Bioorganic and Medicinal Chemistry, Vol. 18, No. 19, 01.10.2010, p. 7113-7120.

Research output: Contribution to journalArticle

Bindi, S, Fancelli, D, Alli, C, Berta, D, Bertrand, JA, Cameron, AD, Cappella, P, Carpinelli, P, Cervi, G, Croci, V, D'Anello, M, Forte, B, Laura Giorgini, M, Marsiglio, A, Moll, J, Pesenti, E, Pittalà, V, Pulici, M, Riccardi-Sirtori, F, Roletto, F, Soncini, C, Storici, P, Varasi, M, Volpi, D, Zugnoni, P & Vianello, P 2010, 'Thieno[3,2-c]pyrazoles: A novel class of Aurora inhibitors with favorable antitumor activity', Bioorganic and Medicinal Chemistry, vol. 18, no. 19, pp. 7113-7120. https://doi.org/10.1016/j.bmc.2010.07.048
Bindi, Simona ; Fancelli, Daniele ; Alli, Cristina ; Berta, Daniela ; Bertrand, Jay A. ; Cameron, Alexander D. ; Cappella, Paolo ; Carpinelli, Patrizia ; Cervi, Giovanni ; Croci, Valter ; D'Anello, Matteo ; Forte, Barbara ; Laura Giorgini, M. ; Marsiglio, Aurelio ; Moll, Juergen ; Pesenti, Enrico ; Pittalà, Valeria ; Pulici, Maurizio ; Riccardi-Sirtori, Federico ; Roletto, Fulvia ; Soncini, Chiara ; Storici, Paola ; Varasi, Mario ; Volpi, Daniele ; Zugnoni, Paola ; Vianello, Paola. / Thieno[3,2-c]pyrazoles : A novel class of Aurora inhibitors with favorable antitumor activity. In: Bioorganic and Medicinal Chemistry. 2010 ; Vol. 18, No. 19. pp. 7113-7120.
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