Cdc7 kinase inhibitors: Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships

Ermes Vanotti; Raffaella Amici; Alberto Bargiotti; Jens Berthelsen; Roberta Bosotti; Antonella Ciavolella; Alessandra Cirla; Cinzia Cristiani; Roberto D'Alessio; Barbara Forte; Antonella Isacchi; Katia Martina; Maria Menichincheri; Antonio Molinari; Alessia Montagnoli; Paolo Orsini; Antonio Pillan; Fulvia Roletto; Alessandra Scolaro; Marcellino Tibolla; Barbara Valsasina; Mario Varasi; Daniele Volpi; Corrado Santocanale

doi:10.1021/jm700956r

Cdc7 kinase inhibitors: Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships

Ermes Vanotti (Lead / Corresponding author), Raffaella Amici, Alberto Bargiotti, Jens Berthelsen, Roberta Bosotti, Antonella Ciavolella, Alessandra Cirla, Cinzia Cristiani, Roberto D'Alessio, Barbara Forte, Antonella Isacchi, Katia Martina, Maria Menichincheri, Antonio Molinari, Alessia Montagnoli, Paolo Orsini, Antonio Pillan, Fulvia Roletto, Alessandra Scolaro, Marcellino TibollaBarbara Valsasina, Mario Varasi, Daniele Volpi, Corrado Santocanale

Drug Discovery Unit

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

88 Citations (Scopus)

Abstract

Cdc7 kinase is an essential protein that promotes DNA replication in eukaryotic organisms. Genetic evidence indicates that Cdc7 inhibition can cause selective tumor-cell death in a p53-independent manner, supporting the rationale for developing Cdc7 small-molecule inhibitors for the treatment of cancers. In this paper, the synthesis and structure-activity relationships of 2-heteroaryl-pyrrolopyridinones, the first potent Cdc7 kinase inhibitors, are described. Starting from 2-pyridin-4-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c] pyridin-4-one, progress toward a simple scaffold, tailored for Cdc7 inhibition, is reported.

Original language	English
Pages (from-to)	487-501
Number of pages	15
Journal	Journal of Medicinal Chemistry
Volume	51
Issue number	3
Early online date	18 Jan 2008
DOIs	https://doi.org/10.1021/jm700956r
Publication status	Published - 14 Feb 2008

Keywords

Inhibition
Inhibitors
Peptides and proteins
Pyrroles
Substituents

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

UN SDGs

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

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10.1021/jm700956r

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Vanotti, E., Amici, R., Bargiotti, A., Berthelsen, J., Bosotti, R., Ciavolella, A., Cirla, A., Cristiani, C., D'Alessio, R., Forte, B., Isacchi, A., Martina, K., Menichincheri, M., Molinari, A., Montagnoli, A., Orsini, P., Pillan, A., Roletto, F., Scolaro, A., ... Santocanale, C. (2008). Cdc7 kinase inhibitors: Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships. Journal of Medicinal Chemistry, 51(3), 487-501. https://doi.org/10.1021/jm700956r

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title = "Cdc7 kinase inhibitors: Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships",

abstract = "Cdc7 kinase is an essential protein that promotes DNA replication in eukaryotic organisms. Genetic evidence indicates that Cdc7 inhibition can cause selective tumor-cell death in a p53-independent manner, supporting the rationale for developing Cdc7 small-molecule inhibitors for the treatment of cancers. In this paper, the synthesis and structure-activity relationships of 2-heteroaryl-pyrrolopyridinones, the first potent Cdc7 kinase inhibitors, are described. Starting from 2-pyridin-4-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c] pyridin-4-one, progress toward a simple scaffold, tailored for Cdc7 inhibition, is reported.",

keywords = "Inhibition, Inhibitors, Peptides and proteins, Pyrroles, Substituents",

author = "Ermes Vanotti and Raffaella Amici and Alberto Bargiotti and Jens Berthelsen and Roberta Bosotti and Antonella Ciavolella and Alessandra Cirla and Cinzia Cristiani and Roberto D'Alessio and Barbara Forte and Antonella Isacchi and Katia Martina and Maria Menichincheri and Antonio Molinari and Alessia Montagnoli and Paolo Orsini and Antonio Pillan and Fulvia Roletto and Alessandra Scolaro and Marcellino Tibolla and Barbara Valsasina and Mario Varasi and Daniele Volpi and Corrado Santocanale",

note = "Copyright: {\textcopyright} 2008 American Chemical Society.",

year = "2008",

month = feb,

day = "14",

doi = "10.1021/jm700956r",

language = "English",

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Vanotti, E, Amici, R, Bargiotti, A, Berthelsen, J, Bosotti, R, Ciavolella, A, Cirla, A, Cristiani, C, D'Alessio, R, Forte, B, Isacchi, A, Martina, K, Menichincheri, M, Molinari, A, Montagnoli, A, Orsini, P, Pillan, A, Roletto, F, Scolaro, A, Tibolla, M, Valsasina, B, Varasi, M, Volpi, D & Santocanale, C 2008, 'Cdc7 kinase inhibitors: Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships', Journal of Medicinal Chemistry, vol. 51, no. 3, pp. 487-501. https://doi.org/10.1021/jm700956r

TY - JOUR

T1 - Cdc7 kinase inhibitors

T2 - Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships

AU - Vanotti, Ermes

AU - Amici, Raffaella

AU - Bargiotti, Alberto

AU - Berthelsen, Jens

AU - Bosotti, Roberta

AU - Ciavolella, Antonella

AU - Cirla, Alessandra

AU - Cristiani, Cinzia

AU - D'Alessio, Roberto

AU - Forte, Barbara

AU - Isacchi, Antonella

AU - Martina, Katia

AU - Menichincheri, Maria

AU - Molinari, Antonio

AU - Montagnoli, Alessia

AU - Orsini, Paolo

AU - Pillan, Antonio

AU - Roletto, Fulvia

AU - Scolaro, Alessandra

AU - Tibolla, Marcellino

AU - Valsasina, Barbara

AU - Varasi, Mario

AU - Volpi, Daniele

AU - Santocanale, Corrado

PY - 2008/2/14

Y1 - 2008/2/14

N2 - Cdc7 kinase is an essential protein that promotes DNA replication in eukaryotic organisms. Genetic evidence indicates that Cdc7 inhibition can cause selective tumor-cell death in a p53-independent manner, supporting the rationale for developing Cdc7 small-molecule inhibitors for the treatment of cancers. In this paper, the synthesis and structure-activity relationships of 2-heteroaryl-pyrrolopyridinones, the first potent Cdc7 kinase inhibitors, are described. Starting from 2-pyridin-4-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c] pyridin-4-one, progress toward a simple scaffold, tailored for Cdc7 inhibition, is reported.

AB - Cdc7 kinase is an essential protein that promotes DNA replication in eukaryotic organisms. Genetic evidence indicates that Cdc7 inhibition can cause selective tumor-cell death in a p53-independent manner, supporting the rationale for developing Cdc7 small-molecule inhibitors for the treatment of cancers. In this paper, the synthesis and structure-activity relationships of 2-heteroaryl-pyrrolopyridinones, the first potent Cdc7 kinase inhibitors, are described. Starting from 2-pyridin-4-yl-1,5,6,7-tetrahydro-pyrrolo[3,2-c] pyridin-4-one, progress toward a simple scaffold, tailored for Cdc7 inhibition, is reported.

KW - Inhibition

KW - Inhibitors

KW - Peptides and proteins

KW - Pyrroles

KW - Substituents

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DO - 10.1021/jm700956r

M3 - Article

C2 - 18201066

AN - SCOPUS:39149143359

SN - 0022-2623

VL - 51

SP - 487

EP - 501

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 3

ER -

Cdc7 kinase inhibitors: Pyrrolopyridinones as potential antitumor agents. 1. Synthesis and structure-activity relationships

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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