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 Severino

Chiara Soncini, Paola Storici, Roberto Tonani, Paola Zugnoni, Paola Vianello

Drug Discovery Unit

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

191 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 language	English
Pages (from-to)	7247-7251
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	49
Issue number	24
Early online date	1 Nov 2006
DOIs	https://doi.org/10.1021/jm060897w
Publication status	Published - 30 Nov 2006

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

Cancer
Inhibition
Inhibitors
Peptides and proteins
Tumors

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm060897w

Cite this

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

@article{90cc73c68c144457ad80105f3b1cb7de,

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

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.",

keywords = "Cancer, Inhibition, Inhibitors, Peptides and proteins, Tumors",

author = "Daniele Fancelli and J{\"u}rgen Moll and Mario Varasi and Rodrigo Bravo and Roberta Artico and Daniela Berta and Simona Bindi and Alexander Cameron and Ilaria Candiani and Paolo Cappella and Patrizia Carpinelli and Walter Croci and Barbara Forte and Giorgini, \{Maria Laura\} and Jan Klapwijk and Aurelio Marsiglio and Enrico Pesenti and Maurizio Rocchetti and Fulvia Roletto and Dino Severino and Chiara Soncini and Paola Storici and Roberto Tonani and Paola Zugnoni and Paola Vianello",

note = "Copyright: {\textcopyright} 2006 American Chemical Society.",

year = "2006",

month = nov,

day = "30",

doi = "10.1021/jm060897w",

language = "English",

volume = "49",

pages = "7247--7251",

journal = "Journal of Medicinal Chemistry",

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publisher = "American Chemical Society",

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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, 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

TY - JOUR

T1 - 1,4,5,6-Tetrahydropyrrolo[3,4-c]pyrazoles

T2 - Identification of a potent aurora kinase inhibitor with a favorable antitumor kinase inhibition profile

AU - Fancelli, Daniele

AU - Moll, Jürgen

AU - Varasi, Mario

AU - Bravo, Rodrigo

AU - Artico, Roberta

AU - Berta, Daniela

AU - Bindi, Simona

AU - Cameron, Alexander

AU - Candiani, Ilaria

AU - Cappella, Paolo

AU - Carpinelli, Patrizia

AU - Croci, Walter

AU - Forte, Barbara

AU - Giorgini, Maria Laura

AU - Klapwijk, Jan

AU - Marsiglio, Aurelio

AU - Pesenti, Enrico

AU - Rocchetti, Maurizio

AU - Roletto, Fulvia

AU - Severino, Dino

AU - Soncini, Chiara

AU - Storici, Paola

AU - Tonani, Roberto

AU - Zugnoni, Paola

AU - Vianello, Paola

PY - 2006/11/30

Y1 - 2006/11/30

N2 - 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.

AB - 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.

KW - Cancer

KW - Inhibition

KW - Inhibitors

KW - Peptides and proteins

KW - Tumors

UR - https://www.scopus.com/pages/publications/33845367377

U2 - 10.1021/jm060897w

DO - 10.1021/jm060897w

M3 - Article

C2 - 17125279

AN - SCOPUS:33845367377

SN - 0022-2623

VL - 49

SP - 7247

EP - 7251

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 24

ER -

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

Abstract

UN SDGs

Keywords

ASJC Scopus subject areas

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