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; Chiara Soncini; Paola Storici; Mario Varasi; Daniele Volpi; Paola Zugnoni; Paola Vianello

doi:10.1016/j.bmc.2010.07.048

Thieno[3,2-c]pyrazoles: A novel class of Aurora inhibitors with favorable antitumor activity

Simona Bindi (Lead / Corresponding author), 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 RolettoChiara Soncini, Paola Storici, Mario Varasi, Daniele Volpi, Paola Zugnoni, Paola Vianello

Drug Discovery Unit

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

34 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 language	English
Pages (from-to)	7113-7120
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	18
Issue number	19
Early online date	25 Jul 2010
DOIs	https://doi.org/10.1016/j.bmc.2010.07.048
Publication status	Published - 1 Oct 2010

Keywords

Anti-cancer
Aurora kinases
Kinase inhibitor
Tumor cell proliferation inhibition

ASJC Scopus subject areas

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Bindi, S., Fancelli, D., Alli, C., Berta, D., Bertrand, J. A., Cameron, A. D., Cappella, P., Carpinelli, P., Cervi, G., Croci, V., D'Anello, M., Forte, B., Giorgini, M. L., Marsiglio, A., Moll, J., Pesenti, E., Pittalà, V., Pulici, M., Riccardi-Sirtori, F., ... 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

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title = "Thieno[3,2-c]pyrazoles: A novel class of Aurora inhibitors with favorable antitumor activity",

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.",

keywords = "Anti-cancer, Aurora kinases, Kinase inhibitor, Tumor cell proliferation inhibition",

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

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doi = "10.1016/j.bmc.2010.07.048",

language = "English",

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pages = "7113--7120",

journal = "Bioorganic and Medicinal Chemistry",

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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, Giorgini, ML, 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

TY - JOUR

T1 - Thieno[3,2-c]pyrazoles

T2 - A novel class of Aurora inhibitors with favorable antitumor activity

AU - Bindi, Simona

AU - Fancelli, Daniele

AU - Alli, Cristina

AU - Berta, Daniela

AU - Bertrand, Jay A.

AU - Cameron, Alexander D.

AU - Cappella, Paolo

AU - Carpinelli, Patrizia

AU - Cervi, Giovanni

AU - Croci, Valter

AU - D'Anello, Matteo

AU - Forte, Barbara

AU - Giorgini, M. Laura

AU - Marsiglio, Aurelio

AU - Moll, Juergen

AU - Pesenti, Enrico

AU - Pittalà, Valeria

AU - Pulici, Maurizio

AU - Riccardi-Sirtori, Federico

AU - Roletto, Fulvia

AU - Soncini, Chiara

AU - Storici, Paola

AU - Varasi, Mario

AU - Volpi, Daniele

AU - Zugnoni, Paola

AU - Vianello, Paola

PY - 2010/10/1

Y1 - 2010/10/1

N2 - 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.

AB - 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.

KW - Anti-cancer

KW - Aurora kinases

KW - Kinase inhibitor

KW - Tumor cell proliferation inhibition

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SN - 0968-0896

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SP - 7113

EP - 7120

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 19

ER -

Thieno[3,2-c]pyrazoles: A novel class of Aurora inhibitors with favorable antitumor activity

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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