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Candidate PET Radioligand Development for Neurofibrillary Tangles: Two Distinct Radioligand Binding Sites Identified in Postmortem Alzheimer’s Disease Brain

[18F]THK-523 and [18F]807 are promising radioligands for imaging neurofibrillary tangles (NFTs) with positron emission tomography (PET) in neurodegenerative diseases, such as Alzheimer’s disease (AD) and traumatic brain injury. Although [18F]THK-523 and [18F]T807 are considered high-affinity selective radioligands for NFTs, uncertainty has existed as to whether PET radioligands for imaging NFTs bind to the same molecular site because in vitro assays for ligands binding to NFTs have been lacking. We labeled THK-523 and T807 with tritium to serve as reference radioligands for in vitro binding assays with AD brain homogenates for newly synthesized ligands. With these radioligands, we identified two distinct binding sites for small molecules, one site with high affinity for THK-523 and the other with high affinity for T807. Moreover, binding assays with [3H]PIB confirmed that the two newly identified binding sites are also distinct from the thioflavin-T binding site where all current clinically useful PET radioligands for imaging beta-amyloid plaque bind with high affinity. The two newly identified binding sites are considered to reside on NFTs rather than on beta-amyloid plaques. Furthermore, we applied all three binding assays to a set of newly prepared compounds, based on chain modifications to THK-523. Some compounds with high affinity and selectivity for the THK-523 binding site emerged from this set, including one with amenability to labeling with fluorine-18, namely, ligand 10b.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H387NO – PubChem

 

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Design and discovery of 2-oxochromene derivatives as liver X receptor beta-selective agonists

In an attempt to molecularly design liver X receptor (LXR) beta-selective agonists, we discovered that the combination of the 2-oxochromene moiety (head) and the imidazoline-2,4-dione moiety (tail) plays an important role in the expression potency and selectivity toward LXRbeta. We synthesized a series of 2-oxochromene derivatives and identified 43 as a LXRbeta-selective agonist that increased the HDL-C level without significantly elevating the TG level and resulted in a decreased lipid-accumulation area in the aortic arch in a high-fat-and-cholesterol-fed Bio F1B hamster. In this manuscript, we report the design, synthesis and pharmacology of these 2-oxochromene derivatives.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H799NO – PubChem

 

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Asymmetric synthesis of N-stereogenic molecules: Diastereoselective double aza-Michael reaction

A novel approach towards the asymmetric synthesis of N-stereogenic molecules via double aza-Michael addition was developed. The diastereomeric ratio can be increased by a thermodynamically controlled isomerization mechanism. Simple separation and functionalization of the products afford N-stereogenic compounds in high enantiomeric purity.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H720NO – PubChem

 

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Rhodium-catalyzed asymmetric cycloisomerization of 1,6-ene-ynamides

The rhodium-catalyzed asymmetric cycloisomerization of heteroatom-bridged 1,6-ene-ynamides proceeded to give high yields of functionalized 3-aza- and oxabicyclo[4.1.0]heptene derivatives with high enantioselectivity, which was achieved by use of a rhodium/chiral diene catalyst. The 1,6-ene-ynamides substituted with 2-oxazolidinone and 2-azetidinone moieties at the alkyne terminus were found to display high reactivity towards the rhodium/chiral diene catalyst, where the chelate coordination of the alkyne moiety and the carbonyl oxygen of the ene-ynamides might be responsible for the high catalytic activity. Copyright

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Oxazolidine – Wikipedia,
Oxazolidine | C3H863NO – PubChem

 

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Fishing with copper acetylides: Selective alkynylation of heteronucleophiles

Copper acetylides are readily available and especially convenient reagents for the alkynylation of a broad range of heteronucleophiles. Upon simple activation with molecular oxygen in the presence of suitable ligands and solvents, they readily transfer their alkyne moiety at room temperature, notably yielding a variety of nitrogen- and phosphorus-substituted alkynes. We report in this manuscript an extensive study of the chemoselectivity of this alkynylation based on quantitative 13C NMR analyses. With suitable ligand/solvent combinations, various phosphorus-based nucleophiles can be alkynylated with excellent levels of selectivity, even in the presence of a large excess of a nitrogen-nucleophile. This chemoselective alkynylation could be further extended to an even more challenging selective alkynylation of a nitrogen-nucleophile over another one, further highlighting the synthetic potential of copper acetylides as alkynylating agents that can selectively ?fish? a nucleophile without affecting others.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H576NO – PubChem

 

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1, 4-SUBSTITUTED PIPERIDINE DERIVATIVES

Described herein are 1,4-substituted piperidine compounds according to Formula (I) that have demonstrated activity as fatty acid synthase inhibitors. Also described herein are pharmaceutical compositions containing the described 1,4-substituted piperidine compounds, and methods of treating diseases mediated by fatty acid synthase, by administering one or more of the compounds or pharmaceutical formulations described herein. Also described herein are methods of synthesizing the compounds described, including the described 1,4-substituted piperidine compounds and synthetic intermediates useful in those syntheses.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H30NO – PubChem

 

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Enantioselective Diels-Alder reactions of 3-(acyloxy)acrylates

Diels-Alder reactions with 3-(acyloxy)acrylates using chiral Lewis acid catalysts have been successfully carried out. These reactions proceed with high enantioselectivity when a chiral Lewis acid derived from Cu(OTf)2 and a bisoxazoline is used. The facility of the reaction is dependent on the nature of the acyloxy group in the dienophile.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H995NO – PubChem

 

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Chemical characterization of MEA degradation in PCC pilot plants operating in Australia

An important step towards commercial scale post-combustion CO2 capture from coal-fired power stations is understanding solvent degradation. Laboratory scale trials have identified three main solvent degradation pathways for 30% MEA: oxidative degradation, carbamate polymerization and formation of heat stable salts. This paper probes the semi-volatile organic compounds produced from a single batch of 30% MEA which was used to capture CO2 from a black coal-fired power station (Tarong, Queensland, Australia) for approximately 700 hours, followed by 500 hours at the brown coal-fired power station (Loy Yang, Victoria, Australia). Comparisons are made between the compounds identified in this aged solvent system with MEA degradation reactions described in literature. Most of semi-volatile compounds tentatively identified by GC/MS have previously been reported in laboratory scale degradation trials. Our preliminary results show low levels of degradation products were present in samples after its use in the pilot plant at Tarong (black coal) and consequent 13 months storage, but much higher concentrations were later found in the same solvent during its at use in the pilot plant at Loy Yang Power (brown coal). Further work includes identifying the cause of poor GC/MS repeatability and investigating the relative rates of reactions described in literature. The impact of inorganic anions and dissolved metals on MEA degradation will also be explored.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H933NO – PubChem

 

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Efficient synthesis of 2-oxazolidinones from epoxides and carbamates catalyzed by amine-functionalized ionic liquids

A series of amine-functionalized ionic liquids were prepared and their catalytic performance was tested in the synthesis of 2-oxazolidinones from epoxides and carbamates. Under optimized reaction conditions, good to excellent yields of various 2-oxazolidinones were achieved with different epoxides and carbamates. Moreover, the amine-functionalized ionic liquid catalyst could be easily recovered and reused without significant loss in activity.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H970NO – PubChem

 

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Adaptability at a protein-DNA interface: Re-engineering the engrailed homeodomain to recognize an unnatural nucleotide

We explore the adaptability at a protein-DNA interface using phage display to re-engineer a homeodomain to specifically recognize a chemically synthesized, unnatural nucleotide. The engineered homeodomain preferentially binds to the modified DNA with affinity and specificity similar to those of natural homeodomains. Copyright

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Oxazolidine – Wikipedia,
Oxazolidine | C3H1004NO – PubChem