- USE OF BENZOTHIAZOLE AMPHIPHILES FOR TREATING TRAUMATIC BRAIN INJURY
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The present invention is directed to methods of reducing symptoms of traumatic brain injury in patients by administering a therapeutically effective amount of a benzothiazole amphiphile compound to a patient suffering from a traumatic brain injury within 0 to 72 hours of incurring the injury.
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Paragraph 0155; 0158
(2019/01/16)
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- BENZOTHIAZOLE AMPHIPHILES
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Disclosed herein, inter alia, are compounds and methods for increasing spine density in a neuron, and for treatment of neuronal diseases and cancer.
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Paragraph 0236
(2017/08/01)
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- Benzothiazole amphiphiles promote the formation of dendritic spines in primary hippocampal neurons
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The majority of excitatory synapses in the brain exist on dendritic spines. Accordingly, the regulation of dendritic spine density in the hippocampus is thought to play a central role in learning and memory. The development of novel methods to control spine density could, therefore, have important implications for treatment of a host of neurodegenerative and developmental cognitive disorders. Herein, we report the design and evaluation of a new class of benzothiazole amphiphiles that exhibit a dosedependent response leading to an increase in dendritic spine density in primary hippocampal neurons. Cell exposure studies reveal that the increase in spine density can persist for days in the presence of these compounds, but returns to normal spine density levels within 24 h when the compounds are removed, demonstrating the capability to reversibly control spinogenic activity. Time-lapse imaging of dissociated hippocampal neuronal cultures shows that these compounds promote a net increase in spine density through the formation of new spines. Biochemical studies support that promotion of spine formation by these compounds is accompanied by Ras activation. These spinogenic molecules were also capable of inhibiting a suspected mechanism for dendritic spine loss induced by Alzheimer-related aggregated amyloid-? peptides in primary neurons. Evaluation of this new group of spinogenic agents reveals that they also exhibit relatively low toxicity at concentrations displaying activity. Collectively, these results suggest that small molecules that promote spine formation could be potentially useful for ameliorating cognitive deficiencies associated with spine loss in neurodegenerative diseases such as Alzheimer disease, and may also find use as general cognitive enhancers.
- Cifelli, Jessica L.,Dozier, Lara,Chung, Tim S.,Patrick, Gentry N.,Yang, Jerry
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p. 11981 - 11992
(2016/07/06)
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- Synthesis, characterization and 11C-radiolabeling of aminophenyl benzothiazoles: Structural effects on the alkylation of amino group
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Several aminophenyl benzothiazoles were prepared with a view to using them as amyloid binding agents for imaging β-amyloid in Alzheimer's disease. These precursors were radiolabeled with 11C-positron-emitting radioisotope using an automated synthesizer and selected radiolabeled compounds were further purified by HPLC. Our results demonstrate that changes in structure have a major influence on the radioactive yield and the ease with which the radiolabel can be introduced. Aminophenyl benzothiazoles with an attached isopropyl group resisted dialkylation perhaps due to steric hindrance caused by this group. Straight chain attachment of methyl, ethyl, butyl, and crotyl groups in the structure decreased the radiochemical yield. Notably, the o-aminophenyl benzothiazole derivatives were difficult to alkylate despite stringent experimental conditions. This reactivity difference is attributed to the hydrogen bonding characteristics of the o-amino group with the nitrogen atom of the thiazole ring. Copyright
- Venkatachalam,Stimson,Bhalla,Pierens,Reutens
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p. 566 - 573
(2014/11/07)
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- A comparative study between para-aminophenyl and ortho-aminophenyl benzothiazoles using NMR and DFT calculations
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Ortho-substituted and para-substituted aminophenyl benzothiazoles were synthesised and characterised using NMR spectroscopy. A comparison of the proton chemical shift values reveals significant differences in the observed chemical shift values for the NH
- Pierens,Venkatachalam,Reutens
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p. 453 - 459
(2014/08/05)
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- Synthesis, characterization and coordination chemistry of aminophenylbenzothiazole substituted 1,4,7-triazacyclononane macrocycles
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The synthesis and spectroscopic characterization of four new 2-(4-aminophenyl)benzothiazole substituted 1,4,7-triazacyclononane derivatives with and without appended pyridyl groups on the macrocycle is reported: 1-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-1,4,7-triazacyclononane (L1), 1-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-4-(2-pyridylmethyl)-1,4, 7-triazacyclononane (L2), 1-(2-(4-N-methylaminophenyl)benzothiazolyl)-2- oxoethyl)-4-(2-pyridylmethyl)-1,4,7-triazacyclononane (L3), 1,4-bis(2- pyridylmethyl)-7-(2-(4-aminophenyl)benzothiazolyl)-2-oxoethyl)-1,4, 7-triazacyclononane (L4). The ligands have been applied in the synthesis of a series of copper (II) complexes, [Cu(L1)(OH2)](ClO4) 2·0.5ACN (C1), [Cu(L3)](ClO4)2· ACN (C2) and [Cu(L4)(OH2)](ClO4)2·0.5THF (C4) whose structures have been determined by X-ray crystallography. As commonly observed for Cu(II) complexes of 1,4,7-triazacyclononane derivatives, the geometry of the metal centre ranges from distorted square pyramidal to pseudo-octahedral. Notably, the amide carbonyl coordinates to the copper(II) centre in C1 and C2 but not in C4 where the presence of an additional pyridyl group results in an N5 coordination sphere.
- Barreto, José,Venkatachalam, Taracad K.,Joshi, Tanmaya,Kreher, Ute,Forsyth, Craig M.,Reutens, David,Spiccia, Leone
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p. 128 - 138
(2013/06/05)
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- One-step synthesis of 2-arylbenzothiazole ('BTA') and -benzoxazole precursors for in vivo imaging of β-amyloid plaques
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We report the simple and efficient synthesis of 2-arylbenzothiazoles ('BTA') and 2-arylbenzoxazoles by direct coupling of benzothiazoles or benzoxazoles with aryl bromides. This method permits direct one-step access to precursors of radiolabeled BTA-1 and
- Alagille, David,Baldwin, Ronald M.,Tamagnan, Gilles D.
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p. 1349 - 1351
(2007/10/03)
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- Thioflavin derivatives for use in antemortem diagnosis of Alzheimer's disease and in vivo imaging and prevention of amyloid deposition
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This invention relates to novel thioflavin derivatives, methods of using the derivatives in, for example, in vivo imaging of patients having neuritic plaques, pharmaceutical compositions comprising the thioflavin derivatives and method of synthesizing the
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- A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain
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The synthesis of a new lipophilic thioflavin-T analogue (2-[4′-(methylamino)phenyl]benzothiazole, 6) with high affinity for amyloid is reported. Intravenous injection of [11C]-labeled 6 in control mice resulted in high brain uptake. Amyloid dep
- Mathis, Chester A.,Bacskai, Brian J.,Kajdasz, Stephen T.,McLellan, Megan E.,Frosch, Matthew P.,Hyman, Bradley T.,Holt, Daniel P.,Wang, Yanming,Huang, Guo-Feng,Debnath, Manik L.,Klunk, William E.
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p. 295 - 298
(2007/10/03)
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