TY - JOUR
T1 - Synthesis and RET protein kinase inhibitory activity of 3-arylureidobenzylidene-indolin-2-ones
AU - Rizzi, Eleonora
AU - Cassinelli, Giuliana
AU - Dallavalle, Sabrina
AU - Lanzi, Cinzia
AU - Cincinelli, Raffaella
AU - Nannei, Raffaella
AU - Cuccuru, Giuditta
AU - Zunino, Franco
PY - 2007/7/15
Y1 - 2007/7/15
N2 - 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.
AB - 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.
KW - Antitumour
KW - Indolinone
KW - Protein kinase
KW - RET
KW - Synthesis
KW - Thyroid cancer
UR - http://www.scopus.com/inward/record.url?scp=34250316191&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250316191&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2007.04.091
DO - 10.1016/j.bmcl.2007.04.091
M3 - Article
C2 - 17499504
AN - SCOPUS:34250316191
VL - 17
SP - 3962
EP - 3968
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 14
ER -