214706-53-3Relevant academic research and scientific papers
Characterization of brain-penetrant pyrimidine-containing molecules with differential microtubule-stabilizing activities developed as potential therapeutic agents for Alzheimer's disease and related tauopathies
Kovalevich, Jane,Cornec, Anne-Sophie,Yao, Yuemang,James, Michael,Crowe, Alexander,Lee, Virginia M.-Y.,John, Trojanowski Q.,Smith, Amos B.,Ballatore, Carlo,Brunden, Kurt R.
, p. 432 - 450 (2016)
The microtubule (MT)-stabilizing protein tau disengages from MTs and forms intracellular inclusions known as neurofibrillary tangles in Alzheimer's disease and related tauopathies. Reduced tau binding to MTs in tauopathies may contribute to neuronal dysfunction through decreased MT stabilization and disrupted axonal transport. Thus, the introduction of brain-penetrant MTstabilizing compounds might normalize MT dynamics and axonal deficits in these disorders. We previously described a number of phenylpyrimidines and triazolopyrimidines (TPDs) that induce tubulin post-translational modifications indicative of MT stabilization. We now further characterize the biologic properties of these small molecules, and our results reveal that these compounds can be divided into two general classes based on the cellular response they evoke. One group composed of the phenylpyrimidines and several TPD examples showed a bell-shaped concentrationresponse effect on markers of MT stabilization in cellular assays. Moreover, these compounds induced proteasome-dependent degradation of a-and b-tubulin and caused altered MT morphology in both dividing cells and neuron cultures. In contrast, a second group comprising a subset of TPD molecules (TPD1) increased markers of stable MTs in a concentration-dependent manner in dividing cells and in neurons without affecting total tubulin levels or disrupting MT architecture. Moreover, an example TPD1 compound was shown to increase MTs in a neuron culture model with induced tau hyperphosphorylation and associated MT deficits. Several TPD1 compounds were shown to be both brain penetrant and orally bioavailable, and a TPD1 example increased MT stabilization in the mouse brain, making these compounds potential candidate therapeutics for neurodegenerative tauopathies such as Alzheimer's disease.
USE OF HYDROPHOBIN AS A SPREADING AGENT
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, (2012/01/12)
The present invention relates to the use of hydrophobin as a spreading agent, in particular in cosmetic or pharmaceutical compositions. The invention further relates to compositions for treating surfaces, in particular cosmetic or pharmaceutical compositions for topical use, that contain hydrophobin as a spreading agent.
Fungicidal trifluorophenyl-triazolopyrimidines
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, (2008/06/13)
The novel compounds of formula I: (R1, R2 and Hal are defined in the specification) show selective fungicidal activity. The new compounds are processed with carriers and adjuvants to fungicidal compositions.
Fungicidal trifluorophenyl-triazolopyrimidines
-
, (2008/06/13)
The novel compounds of formula I: (R1, R2 and Hal are defined in the specification) show selective fungicidal activity. The new compounds are processed with carriers and adjuvants to fungicidal compositions.
