Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene-indolin-2-ones

Eleonora Rizzi; Giuliana Cassinelli; Sabrina Dallavalle; Cinzia Lanzi; Raffaella Cincinelli; Raffaella Nannei; Giuditta Cuccuru; Franco Zunino

doi:10.1016/j.bmcl.2007.04.091

Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene-indolin-2-ones

Eleonora Rizzi, Giuliana Cassinelli, Sabrina Dallavalle, Cinzia Lanzi, Raffaella Cincinelli, Raffaella Nannei, Giuditta Cuccuru, Franco Zunino

Fondazione IRCCS Istituto Nazionale dei Tumori

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

Abstract

A novel series of 3-arylureidobenzylidene-indolin-2-ones was synthesized and their inhibitory activity against Ret tyrosine kinase investigated in comparison with the Ret inhibitor RPI-1 as a reference compound for this series. A few compounds were able to revert the RETC634R oncogene-transformed morphologic phenotype of NIH3T3^MEN2A cells and showed a selective antiproliferative activity against these cells as compared to parental NIH3T3 cells or NIH3T3 cells transformed with a non-tyrosine kinase oncogene (NIH3T3^H-RAS). Inhibition of Ret enzyme activity by effective derivatives was confirmed in a kinase assay. Structure-activity relationship indicated a favourable activity for 5,6-dimethoxyindolinone derivatives with H, OH, or OMe in the para position of the distal aryl ring.

Original language	English
Pages (from-to)	3962-3968
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	14
DOIs	https://doi.org/10.1016/j.bmcl.2007.04.091
Publication status	Published - Jul 15 2007

Keywords

Antitumour
Indolinone
Protein kinase
RET
Synthesis
Thyroid cancer

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Organic Chemistry
Drug Discovery
Pharmaceutical Science

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Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene-indolin-2-ones. / Rizzi, Eleonora; Cassinelli, Giuliana; Dallavalle, Sabrina; Lanzi, Cinzia; Cincinelli, Raffaella; Nannei, Raffaella; Cuccuru, Giuditta; Zunino, Franco.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 17, No. 14, 15.07.2007, p. 3962-3968.

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

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abstract = "A novel series of 3-arylureidobenzylidene-indolin-2-ones was synthesized and their inhibitory activity against Ret tyrosine kinase investigated in comparison with the Ret inhibitor RPI-1 as a reference compound for this series. A few compounds were able to revert the RETC634R oncogene-transformed morphologic phenotype of NIH3T3MEN2A cells and showed a selective antiproliferative activity against these cells as compared to parental NIH3T3 cells or NIH3T3 cells transformed with a non-tyrosine kinase oncogene (NIH3T3H-RAS). Inhibition of Ret enzyme activity by effective derivatives was confirmed in a kinase assay. Structure-activity relationship indicated a favourable activity for 5,6-dimethoxyindolinone derivatives with H, OH, or OMe in the para position of the distal aryl ring.",

keywords = "Antitumour, Indolinone, Protein kinase, RET, Synthesis, Thyroid cancer",

author = "Eleonora Rizzi and Giuliana Cassinelli and Sabrina Dallavalle and Cinzia Lanzi and Raffaella Cincinelli and Raffaella Nannei and Giuditta Cuccuru and Franco Zunino",

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AU - Dallavalle, Sabrina

AU - Lanzi, Cinzia

AU - Cincinelli, Raffaella

AU - Nannei, Raffaella

AU - Cuccuru, Giuditta

AU - Zunino, Franco

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