Synthesis of Arylpiperazine Derivatives as Protease Activated Receptor 1 Antagonists and Their Evaluation as Antiproliferative Agents

Author(s): Andrea Ilaria Zotti, Elena Di Gennaro, Angela Corvino, Francesco Frecentese, Elisa Magli, Elisa Perissutti, Giuseppe Cirino, Fiorentina Roviezzo, Manuela Terranova-Barberio, Federica Iannelli, Giuseppe Caliendo, Vincenzo Santagada, Ferdinando Fiorino, Alfredo Budillon, Beatrice Severino*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 17 , Issue 7 , 2017

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Graphical Abstract:


Background: Protease activated receptor-1 (PAR1) is a G-coupled receptor activated by α-thrombin and other proteases. Several reports have demonstrated the PAR1 involvement in tumorigenesis and tumor progression. In order to investigate on potential use of PAR1 antagonists as antiproliferative agents.

Aims: We have identified a series of arylpiperazine derivatives acting as PAR1 antagonists; the selected molecules have been evaluated for their antiproliferative properties.

Method: All the compounds inhibited the growth of a panel of cell lines expressing PAR1; two of them, compounds 13 and 15, were able to inhibit, in a dose dependent manner, the growth of the selected cell lines with the lowest IC50 values, and were further characterized to define the mechanism responsible for the observed antiproliferative effect.

Result: This study directed us to the identification of two interesting leads that may help to further validate PAR1 as an important therapeutic target for cancer treatment.

Keywords: Antagonists, antiproliferative agents, arylpiperazines, protease activated receptor-1.

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Article Details

Year: 2017
Published on: 18 June, 2017
Page: [973 - 981]
Pages: 9
DOI: 10.2174/1871520616666160926120904
Price: $65

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