677704-48-2Relevant academic research and scientific papers
Development of Gleevec Analogues for Reducing Production of β-Amyloid Peptides through Shifting β-Cleavage of Amyloid Precursor Proteins
Sun, Weilin,Netzer, William J.,Sinha, Anjana,Gindinova, Katherina,Chang, Emily,Sinha, Subhash C.
, p. 3122 - 3134 (2019/04/01)
Imatinib mesylate, 1a, inhibits production of β-amyloid (Aβ) peptides both in cells and in animal models. It reduces both the β-secretase and γ-secretase cleavages of the amyloid precursor protein (APP) and mediates a synergistic effect, when combined with a β-secretase inhibitor, BACE IV. Toward developing more potent brain-permeable leads, we have synthesized and evaluated over 75 1a-analogues. Several compounds, including 2a-b and 3a-c, inhibited production of Aβ peptides with improved activity in cells. These compounds affected β-secretase cleavage of APP similarly to 1a. Compound 2a significantly reduced production of the Aβ42 peptide, when administered (100 mg/kg, twice daily by oral gavage) to 5 months old female mice for 5 days. A combination of compound 2a with BACE IV also reduced Aβ levels in cells, more than the additive effect of the two compounds. These results open a new avenue for developing treatments for Alzheimer's disease using 1a-analogues.
NOVEL PYRIMIDINEAMIDE DERIVATIVES AND THE USE THEREOF
-
Page 40, (2008/06/13)
The invention relates to novel substituted N-(3-benzoylaminophenyl)-4-pyridyl-2-pyrimidinarnine derivatives, processes for the preparation thereof, pharmaceutical compositions containing same, the use thereof optionally in combination with one or more oth
