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Free Fatty Acid Receptor 1 (FFAR1) as an Emerging Therapeutic Target for Type 2 Diabetes Mellitus: Recent Progress and Prevailing Challenges

The free fatty acid receptor 1 (FFAR1/GPR40) amplifies glucose-dependent insulin secretion; therefore, it has attracted widespread attention as a promising antidiabetic target. Current clinical proof of concept also indicates that FFAR1 agonists achieve the initially therapeutic endpoint for the treatment of type 2 diabetes mellitus (T2DM) without the hypoglycemic risk. Thus, many pharmaceutical companies and academic institutes are competing to develop FFAR1 agonists. However, several candidates have been discontinued in clinical trials, often without reporting the underlying reasons. Herein, we review the challenges and corresponding strategies chosen by different medicinal chemistry teams to improve the physicochemical properties, potency, pharmacokinetics, and safety profiles of FFAR1 agonists, with a brief introduction to the biology and pharmacology of related targets.

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Reference£º
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Triclosan and its derivatives as antimycobacterial active agents

Tuberculosis (TB) represents one of the leading causes of morbidity and mortality worldwide. Development of new potential drugs is essential because of the existence of latent TB and expansion of drug-resistant TB forms (multidrug-resistant and extensively drug-resistant tuberculosis). Triclosan is a widely used broad-spectrum biocidal agent. It has been shown to inhibit InhA, an essential enoyl acyl carrier protein reductase, resulting in the lysis of Mycobacterium tuberculosis. Triclosan can be considered as a promising compound for the inhibition of InhA and suppression of mycobacterial growth, because this polychlorinated molecule doesn’t require any activation and it is able to affect the function of InhA directly. This approach enables to circumvent resistance to isoniazid. The aim of this review is to describe current knowledge about triclosan and its analogues as potential antimycobacterial agents.

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Reference£º
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Water promoted one-pot three-step synthesis of novel n-saccharin isoxa-zolines/isoxazoles using KI/oxone under ultrasonic activation

A green and efficient regioselective protocol was developed for the preparation of novel isoxazolines and isoxazoles of N-saccharin derivatives via the water-promoted cycloaddition reaction of nitrile oxides with alkenes and alkynes. It is noteworthy that KI/Oxone/water-promoted one-pot three-component reactions of aldehyde, hydroxylamine hydrochloride, and alkene or alkyne were observed to be very satisfactory. The synthesis of all adducts (4a-j/5a-j) has been carried out by this method with high to excellent yields (70-95%) at 25C within 30 min, using ultrasonic probe. All the new compounds were thoroughly characterized by spectroscopic techniques and also 5b, 5c and 5f were structurally identified by single-crystal X-ray diffraction methods. X-ray crystallography structure analysis clearly supported the regioselectivity of the cycloaddition reaction.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Synthesis of bis-Isoxazole-bis-Ethylene Dinitrate and bis-Isoxazole-tetra-Ethylene Tetranitrate: Potential Energetic Plasticizers

The syntheses and characterizations of two new energetic compounds based on a bis-isoxazole scaffold are presented. The syntheses employ a metal-free [3+2] cycloaddition of an alkyne and a nitrile oxide. In addition, we report the molecular structure of these compounds as determined by single crystal x-ray diffractometry. Both materials have favourable sensitivity properties and low melting points. Their energetic properties indicate potential use as propellant plasticizers.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Synthesis and Biological Activities of Novel Pyrazole Amide Derivatives Containing Substituted Isoxazole Group

In order to find novel pyrazole compounds possessing potent biological activities, a series of novel pyrazole amide derivatives bearing substituted isoxazole moiety were designed and synthesized according to the method of active substructure combination. Their structures were confirmed by 1H NMR, 13C NMR and elemental analysis. The bioassay data indicated that some title compounds had good insecticidal activities. At the concentration of 500 mug/mL, some compounds showed 60%~100% insecticidal activity against Oriental armyworm, and 50%~100% insecticidal activity against Aphis medicaginis. Additionally, some compounds exhibited good anti-cancer activity against HepG2 cells with the IC50 values of 14.2~18.9 mumol/L.

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Reference£º
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Synthesis of 2-halo-2?-azirine-2-carboxylic acid amides and esters by isomerization of 5-(dialkylamino/alkoxy)-substituted isoxazoles, catalyzed by iron(II) sulfate

[Figure not available: see fulltext.] N,N-Dialkylamides and esters of 2-(chloro/bromo/iodo)-2H-azirine-2-carboxylic acids were synthesized by isomerization of 4-halo-5-(dialkylamino/alkoxy)isoxazoles in the presence of catalytic amounts of FeSO4¡¤7H2O. The use of iron(II) sulfate as catalyst, compared to its chloride, provides the advantage of avoiding halide exchange products in isomerization reactions of 4-bromo- and 4-iodoisoxazoles, as well as prevents catalyst deactivation by the 5-amino substituent of isoxazole, compared to rhodium(II) carboxylates.

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Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Development of 1,2,4-triazole-5-thione derivatives as potential inhibitors of enoyl acyl carrier protein reductase (Inha) in tuberculosis.

Tuberculosis (TB) ranks second, next to AIDS making it most formidable disease in the present age. One of the crucial enzymes involved in cell wall synthesis of Mycobacterium tuberculosis, InhA (enoyl acyl carrier protein reductase), one of the crucial enzymes involved in cell wall synthesis of Mycobacterium tuberculosis, has been authenticated as an effective target for anti-mycobacterial drug development. In the current work, novel derivatives of 1,2,4-triazole-5-thione rationally designed, synthesized and spectrally characterized as promising InhA inhibitors. Anti-mycobacterial potential was determined by resazurin microtiter assay using Mtb H37 Rv strain. The mechanism of action of these compounds was confirmed by InhA enzyme inhibition studies. 6b, the most active compound of the series displayed MIC of 0.19 muM in resazurin microtiter assay and InhA inhibition with IC50 of 90 nM.

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Reference£º
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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High-Pressure Characterization of Melt-Castable Biisoxazole Energetics: 3,3?-Biisoxazole-5,5?-bis-(Methylene) Dinitrate and 3,3?-Biisoxazole-4,4?,5,5?-Tetrakis-(Methylene Nitrate)

The high-pressure behavior of 3,3?-biisoxazole-5,5?-bis-(methylene) dinitrate (BIDN) and 3,3?-biisoxazole-4,4?,5,5?-tetrakis-(methylene nitrate) (BITN) have been studied at room temperature to 25 GPa by Raman spectroscopy and powder X-ray diffraction. The Raman spectra, powder patterns, and calculated unit-cell volumes at select pressures show qualitative agreement with first-principles density function theory calculations. Over this pressure range, no evidence of polymorphism was observed. The lack of observed phase changes can be partially attributed to the strengthening of hydrogen bonding observed with pressure increase. These insights point to the potential importance of hydrogen bonding in potential melt-castable materials.

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Reference£º
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Investigation of H atom and free radical behaviour in clathrate hydrates of organic molecules

Clathrate hydrates are icy materials composed of a lattice of water molecules containing well-defined cavities which can accommodate small guest molecules. Their large storage capacity makes clathrates attractive media for a variety of gas storage and separation applications, but there is relatively little information on the chemical stability and diffusion of guest molecules. At the fundamental level inter-cage transition energies have been calculated, but the results need to be tested with experimental data. Ideally this should involve single-atom transport, using an isotopic tracer or spin label. Muonium (Mu = mu+e?) qualifies on both counts. As a single-electron atom with the muon as nucleus it may be considered a light isotope of hydrogen. Furthermore muonium and its reaction products may be monitored by muon spin spectroscopy. In recent years we have used this method to probe H-atom and free radical behaviour in clathrate hydrates. The current work extends studies to benzene and acetone clathrate hydrates. Of note is the simultaneous detection of muonium and muoniated radicals in the same sample. This can happen when Mu is trapped in an empty cavity, remote from its reaction partner. Increase in temperature leads to transport of Mu between cages and results in encounters with reactive guest molecules. By studying the temperature dependence of Mu and radical signals, we have been able to determine the activation energy for transport of Mu between cavities.

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Reference£º
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem

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Chemistry of 3-carbonyl-2-methyl-4-oxo-4H-1-benzopyrans

The review article gives a comprehensive survey of the synthesis and chemistry of the title benzopyrans covering the literature published during 1980 – August 2015.

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Reference£º
Isoxazole – Wikipedia,
Isoxazole | C3H3NO – PubChem