Therapeutic potential of targeting kynurenine pathway in neurodegenerative diseases.

Kynurenine pathway (KP), the primary pathway of L-tryptophan (Trp) metabolism in mammals, contains several neuroactive metabolites such as kynurenic acid (KA) and quinolinic acid (QA). Its imbalance involved in aging and neurodegenerative diseases (NDs) has attracted much interest in therapeutically targeting KP enzymes and KP metabolite-associated receptors, especially kynurenine monooxygenase (KMO). Currently, many agents have been discovered with significant improvement in animal models but only one aryl hydrocarbon receptor (AHR) agonist 30 (laquinimod) has entered clinical trials for treating Huntington's disease (HD).

Dual role of polyglycerol vitamin E succinate in emulsions: An efficient antioxidant emulsifier.

α-Tocopherol, as an oil-soluble vitamin with strong antioxidant activity. It is the most naturally abundant and biologically active form of vitamin E in humans. In this study, a novel emulsifier (PG20-VES) was synthesized by attaching hydrophilic twenty-polyglycerol (PG20) to hydrophobic vitamin E succinate (VES).

Targeting phosphodiesterase 4 as a therapeutic strategy for cognitive improvement.

Phosphodiesterase 4 (PDE4), the largest member of PDE family, is highly expressed in mammalian brain. It selectively hydrolyzes the second messenger cyclic adenosine monophosphate (cAMP), a correlate of brain functions including learning, memory and cognitive abilities. Its inhibition is beneficial to counteract cognitive deficits.

Diastereoselective Access to Triazolo[1,2-]indolines via a Bio-Inspired Oxidative Cyclization of NH-Indoles.

Establishing three-dimensional chemicals by using the C-C π bond of indoles has always been a research hotspot in organic synthesis; however, employing the oxidative C-C π bond of indoles to generate imine which would lead to the N-C π bond cyclization under metal-free conditions is still rare. Here, we report a bio-inspired synthesis of triazolo[1,2-]indolines by the oxidative cyclization between -indoles and azomethine imines with 3,3-dimethyldioxirane as the sole oxidant under metal-free and mild conditions. This finding represents an elegant instance of tri-functionalization of -indoles, which provides rapid access to a broad range of triazolo[1,2-]indolines with tetrahydroisoquinolines in one single step.

Assembly of 5-dibenzo[,]cycloheptenes by a formal [5 + 2] annulation of -aryl alkynyl benzyl alcohols with arenes.

A new synthetic methodology for the synthesis of 5-dibenzo[,]cycloheptenes from -aryl alkynyl benzyl alcohols and arenes a TfO-mediated formal [5 + 2] annulation reaction has been achieved. From this transformation, structurally diverse 5-dibenzo[,]cycloheptenes were achieved in moderate to good yields. This transformation probably involves an intermolecular Friedel-Crafts-type alkylation and a subsequent intramolecular 7- cyclization in one pot, highlighting the high efficiency, regioselectivity, and step-economy of this protocol.

Understanding of the interactions between azole-anion-based ionic liquids and 2-methyl-3-butyn-2-ol from the experimental perspective: the cage effect.

The interactions between azole-anion-based ionic liquids (AILs) and 2-methyl-3-butyn-2-ol (MBY) play an important role in AIL-promoted carboxylative cyclization of MBY with CO. To better understand the interactions between AILs ([P][Im], [P][4-MeIm], and [P][4-BrIm]) and MBY, a detailed investigation from the experimental perspective has been carried out in this study. The results show that the derivative of viscosity () with the mole fraction of AIL () of AIL + MBY mixtures appears to have the maximum value when ≈ 0.

Rhodium/Chiral-Diene-Catalyzed Switchable Asymmetric Divergent Arylation of Enone-Diones.

A rhodium/chiral diene catalytic system is reported for the reaction of enone-diones and arylboronic acids that allows the switchable synthesis of chiral bicyclic products and acyclic products in a controlled manner. The production of bicyclic products containing four contiguous stereocenters is assumed to proceed through the enantioselective arylrhodation of enone-diones with CsCO, forming a rhodium-enolate intermediate, followed by desymmetrization of the diastereotopic diones via aldol cyclization with quantitative diastereoselection and excellent enantiomeric excess. The production of acyclic products is assumed to proceed through the enantioselective hydroarylation of enone-diones with excellent enantiomeric excess in which the aldol cyclization is significantly inhibited by the choice of EtN as a base.

CuCl·2HO/TBHP mediated synthesis of β-enaminones coupling reaction of vinyl azides with aldehydes.

A facile and efficient oxidative functionalization of vinyl azides with aldehydes furnishing a diverse array of β-acylated enaminones was developed. The cross coupling was accomplished in the presence of CuCl·2HO/TBHP and produced the desired β-acylated enaminones in a ()-stereo-selective and atom-economic manner, which make this protocol particularly attractive. In the transformation, the new C-C and C-N bonds were formed a one-pot strategy including the process of radical addition and recombination.

Therapeutic potential of phosphodiesterase inhibitors for cognitive amelioration in Alzheimer's disease.

Alzheimer's disease (AD), one of the greatest threats to human health, is characterized by declined cognition and changed behavior. Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) that play an important role in learning and memory are hydrolyzed by phosphodiesterases (PDEs). Most PDE isoforms are highly expressed in the brain, and the inhibition of PDEs is beneficial to counteract AD.

Design, synthesis, biological evaluation and molecular modeling of N-isobutyl-N-((2-(p-tolyloxymethyl)thiazol-4yl)methyl)benzo[d][1,3] dioxole-5-carboxamides as selective butyrylcholinesterase inhibitors.

Butyrylcholinesterase (BuChE) is recently regarded as a biomarker in progressed Alzheimer's disease (AD). Development of selective BuChE inhibitors has attracted a great deal of interest and may be a viable therapeutic strategy for AD. Recently, we reported the N-isobutyl-N-((2-(p-tolyloxymethyl)thiazol-4-yl)methyl)benzo[d][1,3]dioxole-5-carboxamide (1) as a selective BuChE inhibitor.

HO-mediated room temperature synthesis of 2-arylacetophenones from arylhydrazines and vinyl azides in water.

An environmentally benign, cost-efficient and practical methodology for the room temperature synthesis of 2-arylacetophenones in water has been discovered. The facile and efficient transformation involves the oxidative radical addition of arylhydrazines with α-aryl vinyl azides in the presence of HO (as a radical initiator) and PEG-800 (as a phase-transfer catalyst). From the viewpoint of green chemistry and organic synthesis, the present protocol is of great significance because of using cheap, non-toxic and readily available starting materials and reagents as well as amenability to gram-scale synthesis, which provides an attractive strategy to access 2-arylacetophenones.