10205-71-7Relevant academic research and scientific papers
Metal-chelating benzothiazole multifunctional compounds for the modulation and 64Cu PET imaging of Aβ aggregation
Bandara, Nilantha,Cho, Hong-Jun,Huang, Yiran,Mirica, Liviu M.,Rogers, Buck E.,Sun, Liang,Tran, Diana
, p. 7789 - 7799 (2020)
While Alzheimer's Disease (AD) is the most common neurodegenerative disease, there is still a dearth of efficient therapeutic and diagnostic agents for this disorder. Reported herein are a series of new multifunctional compounds (MFCs) with appreciable affinity for amyloid aggregates that can be potentially used for both the modulation of Aβ aggregation and its toxicity, as well as positron emission tomography (PET) imaging of Aβ aggregates. Firstly, among the six compounds tested HYR-16 is shown to be capable to reroute the toxic Cu-mediated Aβ oligomerization into the formation of less toxic amyloid fibrils. In addition, HYR-16 can also alleviate the formation of reactive oxygen species (ROS) caused by Cu2+ ions through Fenton-like reactions. Secondly, these MFCs can be easily converted to PET imaging agents by pre-chelation with the 64Cu radioisotope, and the Cu complexes of HYR-4 and HYR-17 exhibit good fluorescent staining and radiolabeling of amyloid plaques both in vitro and ex vivo. Importantly, the 64Cu-labeled HYR-17 is shown to have a significant brain uptake of up to 0.99 ± 0.04 percentID per g. Overall, by evaluating the various properties of these MFCs valuable structure-activity relationships were obtained that should aid the design of improved therapeutic and diagnostic agents for AD. This journal is
Intramolecular cascade C-S bond formation: Regioselective synthesis of substituted benzothiazoles
Bose, D. Subhas,Idrees, Mohd.
experimental part, p. 1983 - 1988 (2010/08/13)
Carbon-fluorine bond fission has been coupled with C-S bond formation under metal-free conditions, which is seldom reported in the literature. The intramolecular C-S bond formation reaction takes place by fission of the carbon-fluorine bond in situ, and is believed to proceed through an S NAr mechanism. The approach represents a practical and atom-economical approach for regioselective and metal-free cascade synthesis of substituted benzothiazoles. This one-pot, environmentally benign protocol involves 2-fluoroanilines, benzoyl chlorides and Lawessons reagent under microwave irradiation (5 min) or conventional thermal conditions (3h). Georg Thieme Verlag Stuttgart.
Dess-martin periodinane mediated intramolecular cyclization of phenolic azomethines: A solution-phase strategy toward benzoxazoles and benzothiazoles
Bose, D. Subhas,Idrees, Mohd.
experimental part, p. 398 - 402 (2010/04/03)
Dess-Martin periodinane (DMP), a highly versatile hypervalent iodine(V) reagent, was found to efficiently mediate the intramolecular cyclization of phenolic azomethines/Schiff bases at ambient temperature leading to the rapid and expeditious synthesis of substituted benzoxazoles and benzothiazoles. Furthermore, a solution-phase strategy has been developed by treating the reaction mixtures sequentially with Amberlyst A-26 thiosulfate resin and diisopropylaminomethyl resin (PS-DIEA), which remove excess reagent and byproducts, to give pure products. Georg Thieme Verlag Stuttgart - New York.
A basis for reduced chemical library inhibition of firefly luciferase obtained from directed evolution
Auld, Douglas S.,Zhang, Ya-Qin,Southall, Noel T.,Rai, Ganesha,Landsman, Marc,MacLure, Jennifer,Langevin, Daniel,Thomas, Craig J.,Austin, Christopher P.,Inglese, James
supporting information; experimental part, p. 1450 - 1458 (2009/12/26)
We measured the "draggability" of the ATP-dependent luciferase derived from the firefly Photuris pennsylvanica that was optimized using directed evolution (Ultra-Glo, Promega). Quantitative high-throughput screening (qHTS) was used to determine IC50
Synthesis of 2-arylbenzothiazoles by DDQ-promoted cyclization of thioformanilides; a solution-phase strategy for library synthesis
Bose, D. Subhas,Idrees,Srikanth, Bingi
, p. 819 - 823 (2007/12/29)
Several substituted benzothiazoles were synthesized by the intramolecular cyclization of thioformanilides using 2,6-dichloro-3,5-dicyano-1,4-benzoquinone (DDQ) in dichloromethane at ambient temperature in high yields. The resulting 2-arylbenzothiazoles we
One-step synthesis of 2-arylbenzothiazole ('BTA') and -benzoxazole precursors for in vivo imaging of β-amyloid plaques
Alagille, David,Baldwin, Ronald M.,Tamagnan, Gilles D.
, p. 1349 - 1351 (2007/10/03)
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
Thioflavin derivatives for use in antemortem diagnosis of Alzheimer's disease and in vivo imaging and prevention of amyloid deposition
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Page 15 - 16, (2008/06/13)
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
Synthesis and evaluation of 11C-labeled 6-substituted 2-arylbenzothiazoles as amyloid imaging agents.
Mathis, Chester A,Wang, Yanming,Holt, Daniel P,Huang, Guo-Feng,Debnath, Manik L,Klunk, William E
, p. 2740 - 2754 (2007/10/03)
The synthesis and evaluation of a series of neutral analogues of thioflavin-T (termed BTA's) with high affinities for aggregated amyloid and a wide range of lipophilicities are reported. Radiolabeling with high specific activity [(11)C]methyl iodide provided derivatives for in vivo evaluation. Brain entry in control mice and baboons was high for nearly all of the analogues at early times after injection, but the clearance rate of radioactivity from brain tissue varied by more than 1 order of magnitude. Upon the basis of its rapid clearance from normal mouse and baboon brain tissues, [N-methyl-(11)C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole (or [(11)C]6-OH-BTA-1) was selected as the lead compound for further evaluation. The radiolabeled metabolites of [(11)C]6-OH-BTA-1 were polar and did not enter brain. The binding affinities of [N-methyl-(3)H]6-OH-BTA-1 for homogenates of postmortem AD frontal cortex and synthetic Abeta(1-40) fibrils were similar (K(d) = 1.4 nM and 4.7 nM, respectively), but the ligand-to-Abeta peptide binding stoichiometry was approximately 400-fold higher for AD brain than Abeta(1-40) fibrils. Staining of AD frontal cortex tissue sections with 6-OH-BTA-1 indicated the selective binding of the compound to amyloid plaques and cerebrovascular amyloid. The encouraging in vitro and in vivo properties of [(11)C]6-OH-BTA-1 support the choice of this derivative for further evaluation in human subject studies of brain Abeta deposition.
Thioflavin derivatives for use in antemortem diagnosis of alzheimer's disease and vivo imaging and prevention of amyloid deposition
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, (2008/06/13)
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
