5515-13-9Relevant academic research and scientific papers
Studies on the ATP Binding Site of Fyn Kinase for the Identification of New Inhibitors and Their Evaluation as Potential Agents against Tauopathies and Tumors
Tintori, Cristina,La Sala, Giuseppina,Vignaroli, Giulia,Botta, Lorenzo,Fallacara, Anna Lucia,Falchi, Federico,Radi, Marco,Zamperini, Claudio,Dreassi, Elena,Dello Iacono, Lucia,Orioli, Donata,Biamonti, Giuseppe,Garbelli, Mirko,Lossani, Andrea,Gasparrini, Francesca,Tuccinardi, Tiziano,Laurenzana, Ilaria,Angelucci, Adriano,Maga, Giovanni,Schenone, Silvia,Brullo, Chiara,Musumeci, Francesca,Desogus, Andrea,Crespan, Emmanuele,Botta, Maurizio
, p. 4590 - 4609 (2015/06/30)
Fyn is a member of the Src-family of nonreceptor protein-tyrosine kinases. Its abnormal activity has been shown to be related to various human cancers as well as to severe pathologies, such as Alzheimer's and Parkinson's diseases. Herein, a structure-based drug design protocol was employed aimed at identifying novel Fyn inhibitors. Two hits from commercial sources (1, 2) were found active against Fyn with Ki of about 2 μM, while derivative 4a, derived from our internal library, showed a Ki of 0.9 μM. A hit-to-lead optimization effort was then initiated on derivative 4a to improve its potency. Slightly modifications rapidly determine an increase in the binding affinity, with the best inhibitors 4c and 4d having Kis of 70 and 95 nM, respectively. Both compounds were found able to inhibit the phosphorylation of the protein Tau in an Alzheimer's model cell line and showed antiproliferative activities against different cancer cell lines. (Chemical Equation Presented).
Design, synthesis and biological evaluation of 5-amino-1H-pyrazole-4- carboxamide derivatives as potential antitumor agents
Yang, Baowei,Liu, Wukun,Mei, Yicheng,Huang, Dandan,Qian, Hai,Huang, Wenlong,Gust, Ronald
, p. 749 - 755 (2014/07/07)
Adenosine deaminase (ADA) inhibitors have been found to have antitumor activities. Here, thirteen potential adenosine deaminase inhibitors 5-amino-1H-pyrazole-4-carboxamide derivatives were designed, synthesized and screened for antitumor activities. Comp
Pyrrole derivatives as potent inhibitors of lymphocyte-specific kinase: Structure, synthesis, and SAR
Takayama, Tetsuo,Umemiya, Hiroki,Amada, Hideaki,Yabuuchi, Tetsuya,Shiozawa, Fumiyasu,Katakai, Hironori,Takaoka, Akiko,Yamaguchi, Akie,Endo, Mayumi,Sato, Masakazu
scheme or table, p. 108 - 111 (2010/03/30)
We have described the synthesis, enzyme inhibitory activity, structure-activity relationships, and proposed binding mode of a novel series of pyrrole derivatives as lymphocyte-specific kinase (Lck) inhibitors. The most potent analogs exhibited good enzyme inhibitory activity (IC50s 10 nM) for Lck kinase inhibition.
One-pot synthesis of tetrasubstituted pyrazoles - Proof of regiochemistry
Hanefeld, Ulf,Rees, Charles W.,White, Andrew J. P.,Williams, David J.
, p. 1545 - 1552 (2007/10/03)
1-Alkyl-5-amino-3-aryl-4-cyanopyrazoles, useful intermediates for fused heterocyclic systems, are synthesised by a one-pot three-step procedure from acid chlorides, malononitrile and alkylhydrazines. The regiochemistry of the hydrazine incorporation was p
