122306-01-8Relevant articles and documents
A Copper Complex of a Thiosemicarbazone-Pyridylhydrazone Ligand Containing a Vinylpyridine Functional Group as a Potential Imaging Agent for Amyloid-β Plaques
McInnes, Lachlan E.,Noor, Asif,Roselt, Peter D.,McLean, Catriona A.,White, Jonathan M.,Donnelly, Paul S.
, p. 827 - 834 (2019)
Complexes containing positron-emitting radionuclides of copper have the potential to be of use for diagnostic imaging with positron emission tomography. Alzheimer's disease is characterised by the presence of amyloid-β plaques in the brain. A new thiosemicarbazone-pyridyl hydrazone tetradentate ligand with a pyridyl-4-vinylpyridine functional group was prepared with the aim of making a copper complex that binds to amyloid-β plaques to assist in the diagnosis of Alzheimer's disease. The ligand forms a charge neutral complex with copper(ii) that was characterised by X-ray crystallography and the electrochemical behaviour of the complex was investigated by cyclic voltammetry. The new ligand can be radiolabelled with positron-emitting copper-64 at room temperature in excellent radiochemical yields. The new complex interacts with synthetic amyloid-β fibrils and binds amyloid-β plaques present in post-mortem Alzheimer's disease brain tissue.
Synthesis of a Non-Heme Template for Attaching Four Peptides: An Approach to Artificial Iron (II)-Containing Peroxidases
Van Den Heuvel, Marco,Van Den Berg, Tieme A.,Kellogg, Richard M.,Choma, Christin T.,Feringa, Ben L.
, p. 250 - 262 (2004)
We are developing all-synthetic model cofactor-protein complexes in order to define the parameters controlling non-natural cofactor activity. The long-term objective is to establish the theoretical and practical basis for designing novel enzymes. A non-heme pentadentate ligand (N4Py) is being developed as a template for the site-specific attachment of a designed four-helix bundle. Previously, we attached two unprotected peptides via CH 2Cl handles to N4Py. In the presence of hydrogen peroxide, the iron(II) complex of this ligand (2a) generates an FeIIIOOH intermediate (3a) that can oxidize a wide variety of organic compounds. Here, we describe the synthesis of 27, a N4Py derivative in which four three-carbon spacers have been introduced, and show that four copies of an unprotected, single-cysteine peptide can be coupled via a thioether linkage to the ligand. In addition, a divergent synthesis route to tetrabromide ligand lb has also been developed, providing the opportunity to prepare alternative pentadentate ligands efficiently by four cross-coupling reactions on a single molecule. Also, two of the four bromides of lb can be selectively addressed by magnesium-bromide exchange.
CDK4/6 INHIBITORS AND USE THEREOF
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Paragraph 731-733, (2019/03/05)
The present disclosure relates to a compound of formula (I), or a pharmaceutically acceptable salt, a solvate, a stereoisomer, or tautomer thereof, a pharmaceutical composition comprising a compound of formula (A) or formula (B), and any subgenera thereof, and use of said compounds and compositions thereof, wherein R1, R2, R3a, R3b, R5, R6, X1, X2, Y and n are described herein.
Rhenium and technetium complexes of thioamide derivatives of pyridylhydrazine that bind to amyloid-β plaques
Fletcher, Scott P.,Noor, Asif,Hickey, James L.,McLean, Catriona A.,White, Jonathan M.,Donnelly, Paul S.
, p. 1139 - 1151 (2018/07/13)
Abstract: Age-associated deposition of amyloid-β in cerebral blood vessels, a condition referred to as cerebral amyloid angiopathy, can contribute to stroke and dementia. This research aimed to design new radioactive technetium-99?m complexes that bind to amyloid-β plaques that have the potential to assist in diagnosis of cerebral amyloid angiopathy using single-photon-emitted computed tomography (SPECT) imaging. Six new pyridylthiosemicarbazide ligands containing either benzofuran or styrylpyridyl functional groups that are known to selectively bind to amyloid plaques were prepared. Non-radioactive isotopes of technetium are not available so rhenium was used as a surrogate for exploratory chemistry. The new ligands were used to prepare well-defined [Re-oxo]3+ complexes where two pyridylthiosemicarbazide ligands were coordinated to a single metal ion to give bivalent complexes with two amyloid-β targeting functional groups. The interaction of the [Re-oxo]3+ complexes with synthetic amyloid-β1-42 and with amyloid plaques in human brain tissue was investigated. Two ligands were selected to develop methods to prepare their [99mTc-oxo]3+ complexes at the tracer level. These technetium-99?m complexes are likely to be isostructural to their rhenium-oxo analogues.
Benzimidazole derivatives, preparation methods and uses theirof
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Page/Page column 31, (2018/12/01)
The present invention relates to benzimidazole compounds useful in treating for protein kinase-associated disorders. There is also a need for compounds useful in the treatment or prevention of one or more symptoms of cancer, transplant rejections. Furthermore, there is a need for methods for modulating the activity of protein kinases, such as CDK4 and/or CDK6, using the compounds provided herein.
Hydroxypurine compound and use thereof
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Paragraph 0517; 0521; 0522; 0523, (2016/10/08)
The invention discloses a hydroxypurine compound and a use of the hydroxypurine compound as a PDE2 or TNFa inhibitor and concretely discloses a compound shown in the formula (I) and its tautomer or pharmaceutically acceptable salt.
Synthesis of Oxorhenium(V) and Oxotechnetium(V) Complexes That Bind to Amyloid-β Plaques
Hayne, David J.,White, Jonathan M.,McLean, Catriona A.,Villemagne, Victor L.,Barnham, Kevin J.,Donnelly, Paul S.
, p. 7944 - 7953 (2016/08/24)
Alzheimer's disease is characterized by the presence of amyloid plaques in the brain. The primary constituents of the plaques are aggregated forms of the amyloid-β (Aβ) peptide. With the goal of preparing technetium-99m complexes that bind to Aβ plaques with the potential to be diagnostic imaging agents for Alzheimer's disease, new tetradentate ligands capable of forming neutral and lipophilic complexes with oxotechentium(V) and oxorhenium(V) were prepared. Nonradioactive isotopes of technetium are not available so rhenium was used as a surrogate for exploratory chemistry. Two planar tetradentate N3O ligands were prepared that form charge-neutral complexes with oxorhenium(v) as well as a ligand featuring a styrylpyridyl functional group designed to bind to Aβ plaques. All three ligands formed complexes with oxorhenium(V), and each complex was characterized by NMR spectroscopy, mass spectrometry, and X-ray crystallography. The oxorhenium(V) complex with a styrylpyridyl functional group binds to Aβ plaques present in post-mortem human brain tissue. The chemistry was extrapolated to technetium-99m at the tracer level for two of the ligands. The resulting oxotechnetium(V) complexes were sufficiently lipophilic and charge-neutral to suggest that they have the potential to cross the blood-brain barrier but exhibited modest stability with respect to exchange with histidine. The chemistry presented here identifies a strategy to integrate styrylpyridyl functional groups into tetradentate ligands capable of forming complexes with [M=O]3+ cores (M = Re or Tc).
INHIBITORS OF PROTEIN TYROSINE KINASE ACTIVITY
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Paragraph 000299-000300, (2013/04/13)
The present invention provides new compounds and methods for treating a disease responsive to inhibition of kinase activity, for example a disease responsive to inhibition of protein tyrosine kinase activity, for example a disease responsive to inhibition of protein tyrosine kinase activity of growth factor receptors, for example a disease responsive to inhibition of receptor type tyrosine kinase signaling, or for example, a disease responsive to inhibition of VEGF receptor signaling.
METALLOENZYME INHIBITOR COMPOUNDS
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Page/Page column 105-108, (2013/02/28)
The instant invention describes compounds having metalloenzyme modulating activity, and methods of treating diseases, disorders or symptoms thereof mediated by such metalloenzymes.
Synthesis and optoelectronic properties of a carbazole-modified platinum(ii) complex in polymer light-emitting devices
Luo, Jian,Liu, Yu,Shi, Danyan,Wang, Yafei,Zhang, Zhiyong,Yu, Junting,Lei, Gangtie,Chen, Qing,Li, Jianmin,Deng, Xianping,Zhu, Weiguo
scheme or table, p. 1074 - 1081 (2012/03/22)
To improve opto-electronic properties and efficiently suppress excimer emission, a phenylpyridine (ppy)-based platinum(ii) complex (C 16OCz-ppy)Pt(acac) was synthesized and characterized, where C 16OCz-ppy is a 2-phenylpyridine deriv
