TY - JOUR
T1 - Synthesis of substituted 3-amino-N-phenyl-1H-indazole-1-carboxamides endowed with antiproliferative activity
AU - Grimaudo, Stefania
AU - Raimondi, Maria Valeria
AU - Cascioferro, Stella Maria
AU - Raffa, Demetrio
AU - Pipitone, Rosaria Maria
AU - Plescia, Fabiana
AU - Maggio, Benedetta
AU - Plescia, Salvatore
AU - Daidone, Giuseppe
AU - Di Cristina, Antonietta
PY - 2011
Y1 - 2011
N2 - Several new N-phenyl-1H-indazole-1-carboxamides 1c–h and 4l,m were prepared by reacting phenyl isocyanate derivatives 3a,b with 3-amino-1H-indazole derivatives 2c,e,g or 1H-indazole 2l respectively. Chemical transformations of compounds 1a,b and 1g,h gave 3-acetamido-N-phenyl-1H-indazole-1-carboxamide derivatives 5a,b, and 3,5-diamino-N-phenyl-1H-indazole-1-carboxamide derivatives 4i, j respectively. Finally, 3,5-diacetamido-N-phenyl-1H-indazole-1-carboxamide derivatives 6a,b were prepared by acetylation of 4i, j. Some of synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell lines panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). Compound 1c, the most active of the series, was able to inhibit cell growth showing GI50 values in the 0.041–33.6 μM range, mean GI50 1.90 μM, being very effective against colon and melanoma cell lines. Cell cycle analysis in K562 cells showed that 1c causes a marked increase of cells in G0–G1 phase. Moreover, it increases the ratio between hypophosphorylated pRb and total pRb.
AB - Several new N-phenyl-1H-indazole-1-carboxamides 1c–h and 4l,m were prepared by reacting phenyl isocyanate derivatives 3a,b with 3-amino-1H-indazole derivatives 2c,e,g or 1H-indazole 2l respectively. Chemical transformations of compounds 1a,b and 1g,h gave 3-acetamido-N-phenyl-1H-indazole-1-carboxamide derivatives 5a,b, and 3,5-diamino-N-phenyl-1H-indazole-1-carboxamide derivatives 4i, j respectively. Finally, 3,5-diacetamido-N-phenyl-1H-indazole-1-carboxamide derivatives 6a,b were prepared by acetylation of 4i, j. Some of synthesized compounds were evaluated for their in vitro antiproliferative activity against the full NCI tumor cell lines panel derived from nine clinically isolated cancer types (leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast). Compound 1c, the most active of the series, was able to inhibit cell growth showing GI50 values in the 0.041–33.6 μM range, mean GI50 1.90 μM, being very effective against colon and melanoma cell lines. Cell cycle analysis in K562 cells showed that 1c causes a marked increase of cells in G0–G1 phase. Moreover, it increases the ratio between hypophosphorylated pRb and total pRb.
KW - 3-amino-N-phenyl-1H-indazole-1-carboxamides
KW - Antiproliferative agents
KW - G0–G1 arrest
KW - pRb
KW - 3-amino-N-phenyl-1H-indazole-1-carboxamides
KW - Antiproliferative agents
KW - G0–G1 arrest
KW - pRb
UR - http://hdl.handle.net/10447/52394
M3 - Article
VL - 46
SP - 168
EP - 174
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
SN - 0223-5234
ER -