Synthesis and antiproliferative activity of 3-amino-N-phenyl-1H-indazole-1-carboxamides

Giuseppe Daidone, Stella Maria Cascioferro, Benedetta Maggio, Domenico Schillaci, Salvatore Plescia, Rosaria Maria Pipitone, Stefania Grimaudo, Demetrio Raffa, Maria Valeria Raimondi, Rosaria M. Pipitone, Antonietta Di Cristina, Stefania Grimaudo, Manlio Tolomeo, Fiorella Meneghetti, Gabriella Bombieri, Antonietta Di Cristina, Giorgio Gallo

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22 Citazioni (Scopus)

Abstract

A series of new 3-amino-N-phenyl-1H-indazole-1-carboxamides 10 have been prepared from commercially available phenyl isocyanate precursors 8 and 3-aminoindazole 9. Some of the synthesized compounds were evaluated for their in vitro antineoplastic activity against 60 human cell lines derived from seven clinically isolated cancer types (lung, colon, melanoma, renal, ovarian, brain, and leukemia) according to the NCI standard protocol. The test results indicated that the 3-amino-1H-indazole-1-carboxamides 10 were endowed with an interesting anti-proliferative activity. The most active compounds of this series, 10d and 10e, were able to inhibit cell growth of many neoplastic cell lines at concentrations lower than 1µM (0.0153µM in SR leukemia) causing a block in G0-G1 phase of cell cycle. Analysis of pRb expression showed that these two compounds increased the ratio between underphosphorylated pRb and total pRb. The X-ray structure of 10w, confirmed the 3-amino-N-phenyl-1H-indazole-1-carboxamide structure of compounds 10.
Lingua originaleEnglish
pagine (da-a)165-178
Numero di pagine14
RivistaEuropean Journal of Medicinal Chemistry
Volume44
Stato di pubblicazionePublished - 2009

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All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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