Identification of potent c-Src inhibitors strongly affecting the proliferation of human neuroblastoma cells
摘要:
Neuroblastoma (NB) represents the most common extracranial paediatric solid tumor for which no specific FDA-approved treatment is currently available. The tyrosine kinase c-Src has been reported to play an important role in the differentiation, cell-adhesion and survival of NB cells. Starting from dual Src/Abl inhibitors previously found active in NB cell lines (1-3), small modification of the original structures almost abolished the Abl activity with a contemporary improvement of affinity and specificity for cSrc. Among the synthesized compounds, the most potent c-Src inhibitor (10a) showed a very interesting antiproliferative activity in SH-SY5Y cells with an IC50 of 80 nM and a favourable ADME profile. A 3D SAR analysis was also attempted and may guide the design of more potent c-Src inhibitors as potential agents for NB treatment. (C) 2011 Elsevier Ltd. All rights reserved.
Synthesis and hypoglycemic activity of N-alkylated hydrazonopropionic acids
作者:Hans Peter Wolff、Hans F. Kuehnle
DOI:10.1021/jm00148a011
日期:1985.10
A series of N-alkylated 2-hydrazonopropionic acids have been synthesized and evaluated for their hypoglycemicactivity. Most of the compounds exhibit a remarkable blood glucose lowering activity in fasted guinea pigs. Some of the structural variables studied were the effects of branching, unsaturation, or substitution on the alkyl side chain and the effect of nuclear substitution on the aralkyl analogues