- SUBSTITUTED 6-(1H-PYRAZOL-1-YL)PYRIMIDIN-4-AMINE DERIVATIVES AND USES THEREOF
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The present invention covers substituted 6-(1H-pyrazol-1-yl)pyrimidin-4-amine compounds of general formula (I) as described and defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds, and the use of said compounds for manufacturing pharmaceutical compositions for the treatment or prophylaxis of diseases, in particular for the treatment and/or prophylaxis of cardiovascular and renal diseases, as a sole agent or in combination with other active ingredients.
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- 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
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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).
- 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
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p. 4590 - 4609
(2015/06/30)
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- Design, synthesis and biological evaluation of 5-amino-1H-pyrazole-4- carboxamide derivatives as potential antitumor agents
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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
- Yang, Baowei,Liu, Wukun,Mei, Yicheng,Huang, Dandan,Qian, Hai,Huang, Wenlong,Gust, Ronald
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p. 749 - 755
(2014/07/07)
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- MODULATION OF PROTEIN TRAFFICKING
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Compounds and compositions are provided for treatment or amelioration of one or more disorders characterized by defects in protein trafficking. A method of treating a disorder characterized by impaired protein trafficking includes administering to a subject or contacting a cell with a compound of Formula I: [formula here] or pharmaceutically acceptable salts or derivatives thereof.
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Page/Page column 168
(2009/06/27)
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- INHIBITION OF ALPHA-SYNUCLEIN TOXICITY
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Compounds and compositions are provided for treatment or amelioration of one or more symptoms of α-synuclein toxicity, α-synuclein mediated diseases or diseases in which α-synuclein fibrils are a symptom or cause of the disease.
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