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A synthesis of a benzodioxinic analog of 8-methyoxypsoralen (8-MOP), in 12 steps from the commercially available 6-acetyl-2,3-dihydro-1,4-benzodioxin is described.

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Asymmetric reductive amination of poorly nucleophilic sulfonamides was realized in the presence of nickel catalysts and titanium alkoxide. A wide range of ketones, including enolizable ketones and some biaryl ones, were converted into sulfonamides in excellent enantiomeric excess. The cyclization of sulfamates and intermolecular reductive amination of a diarylphosphinamide were also successful. Formic acid was used as a safe and economic surrogate of high-pressure hydrogen gas.

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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The present invention relates to 1-alkyl-3-aniline-5-aryl-pyrazole derivatives and pharmaceutically acceptable salts thereof, processes for preparing them, pharmaceutical compositions containing them and their use in therapy, according to Formula (I). The invention particularly relates to positive allosteric modulators of nicotinic acetylcholine receptors, such positive allosteric modulator having the capability to increase the efficacy of nicotinic receptor agonists.

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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While mu opioid receptor (MOR) agonists are especially effective as broad-spectrum pain relievers, it has been exceptionally difficult to achieve a clear separation of analgesia from many problematic side effects. Recently, many groups have sought MOR agonists that induce minimal betaarrestin-mediated signaling because MOR agonist-treated betaarrestin2 knockout mice were found to display enhanced antinociceptive effects with significantly less respiratory depression and tachyphylaxis. Substantial data now exists to support the premise that G protein signaling biased MOR agonists can be effective analgesic agents. We recently showed that, within a chemical series, the degree of bias correlates linearly with the magnitude of the respiratory safety index. Herein we describe the synthesis and optimization of piperidine benzimidazolone MOR agonists that together display a wide range of bias (G/betaarr2). We identify structural features affecting potency and maximizing bias and show that many compounds have desirable properties, such as long half-lives and high brain penetration.

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Human 5-lipoxygenase (5-LOX) is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related disorders. Our previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds, 3a and 3b, exhibiting a potent inhibitory profile against 5-LOX with IC50 values less than 1 mumol/L in cell-based assays. Here, we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fused-ring system. Several new compounds exhibited more potent inhibitory activity than the lead compounds against 5-LOX. In particular, compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity, but also significantly decreased infarct damage in a mouse model of cerebral ischemia. Molecular docking analysis further confirmed the consistency of our theoretical results and experimental data. In conclusion, the excellent in vitro and in vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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A one-step conversion of ketones into N-acetyl enamides was developed. The process employs safe and inexpensive reagents, proceeds under mild conditions, and tolerates diverse functional groups. The addition of edte (N,N,N ,N -tetrakis(2-hydroxyethyl)ethylenediamine) prior to workup enables water solubilization of Ti alkoxides and allows a simple extractive workup. Copyright

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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(Chemical Equation Presented) Easily modified: the electronic and steric properties of a ruthenium catalyst highly active for C-H bond activation (see scheme) can be modified by fine-tuning the ligand. This makes this catalytic system very versatile as it allows functionalization of a variety of substrates. The catalyst is generated in situ from a stable and easily available ruthenium(II) source.

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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A novel and efficient formal [4 + 2+1] annulation of aryl methyl ketones and 2-aminobenzyl alcohols for the synthesis of benzo[e][1,4]diazepin-3-ones is reported. This reaction successfully affords diverse seven-membered ring lactams via dual C-O bond cleavage. A preliminary mechanistic study showed that a multicomponent dicyclization and ring-opening sequence might occur, with the introduction of methyl sulfide proposed as the last step. This efficient strategy with mild reaction conditions and a broad substrate scope has potential applications in chemistry and medicine.

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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The fungal plasma membrane H+-ATPase (Pma1p) is a potential target for the discovery of new antifungal agents. Surprisingly, no structure?activity relationship studies for small molecules targeting Pma1p have been reported. Herein, we disclose a LEGO-inspired fragment assembly strategy for the design, synthesis, and discovery of benzo[d]thiazoles containing a 3,4-dihydroxyphenyl moiety as potential Pma1p inhibitors. A series of 2-(benzo[d]thiazol-2-ylthio)-1-(3,4-dihydroxyphenyl)ethanones was found to inhibit Pma1p, with the most potent IC50 value of 8 mum in an in vitro plasma membrane H+-ATPase assay. These compounds were also found to strongly inhibit the action of proton pumping when Pma1p was reconstituted into liposomes. 1-(3,4-Dihydroxyphenyl)-2-((6-(trifluoromethyl)benzo[d]thiazol-2-yl)thio)ethan-1-one (compound 38) showed inhibitory activities on the growth of Candida albicans and Saccharomyces cerevisiae, which could be correlated and substantiated with the ability to inhibit Pma1p in vitro.

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Studies on the discovery of tyrosinase enzyme inhibitors and exploration for better cytotoxic agents remain an important line in drug discovery and development. A series of synthetic chalcones and pyrazoline derivatives was evaluated for their inhibitory effects on the diphenolase activity of mushroom tyrosinase. The effects of these compounds on proliferation and microtubule assembly were also evaluated in seven different cancer cell lines. The results revealed that some of the synthetic compounds showed significant inhibitory activity, with four compounds being more potent tyrosinase inhibitors than the reference standard inhibitor kojic acid. Several compounds were toxic to cancer cell lines. Compound 1a was found to possess the highest anticancer activity towards all cell lines with an IC50 in the range of 0.9-2.2 muM. Seven of the compounds showed considerable tubulin polymerization activity at a concentration of 25 muM. Molecular modeling studies of these synthetic compounds were performed to investigate their interactions with the tyrosinase enzyme. The structure-activity relationship (SAR) study using in-silico analysis matched well with the in vitro tumour cell inhibitory activity.

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Reference:
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem