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

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
Page: [973 - 981]
Pages: 9
DOI: 10.2174/1871520616666160926120904
Price: $58

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