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MODULATORS OF THE INTEGRATED STRESS PATHWAY

Provided herein are compounds, compositions, and methods useful for modulating the integrated stress response (ISR) and for treating related diseases; disorders and conditions.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Discovery of novel phenylpyridone derivatives as potent and selective MCH1R antagonists

The design, synthesis and structure-activity relationships of a novel class of N-phenylpyridone MCH1R antagonists are described. The core part of the N-phenylpyridone structure was newly designed and the side chain moieties that were attached to the core part were extensively explored. As a result of optimization of the N-phenylpyridone leads, we successfully developed the orally available, and brain-penetrable MCH1R selective antagonist 7c, exhibiting excellent anti-obese effect in diet-induced obese (DIO) mice.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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Hydrogenation of Esters to Alcohols Catalyzed by Defined Manganese Pincer Complexes

The first manganese-catalyzed hydrogenation of esters to alcohols has been developed. The combination of Mn(CO)5Br with [HN(CH2CH2P(Et)2)2] leads to a mixture of cationic and neutral Mn PNP pincer complexes, which enable the reduction of various ester substrates, including aromatic and aliphatic esters as well as diesters and lactones. Notably, related pincer complexes with isopropyl or cyclohexyl substituents showed very low activity.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

Properties and Exciting Facts About 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine

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Design, synthesis and pharmacological activity of novel enantiomerically pure phosphonic acid-based NAALADase inhibitors

Inhibitors of NAALADase have shown promise for a variety of diseases associated with glutamate excitotoxicity, and could be useful for the diagnosis and therapy of prostate cancer. A series of novel enantiomerically pure 2-(phosphonomethyl)pentanedioic acid (2-PMPA) based NAALADase inhibitors were synthesized. These compounds were prepared from previously reported (S)-2-(hydroxyphosphinoylmethyl)pentanedioic acid benzyl ester 4. Biological test results showed that the new compounds are good to outstanding NAALADase inhibitors. Compounds 8b and 10b showed activity similar to the known potent inhibitor (S)-2-PMPA. Fluorescently labeled inhibitor 19b may potentially be used to study binding to prostate cancer cells by fluorescence microscopy, and siderophore-containing inhibitor 21b may be useful for detection of prostate-derived cancer cells by magnetic resonance imaging (MRI). This journal is The Royal Society of Chemistry.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

Discovery of 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine

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Discovery, characterization and biological evaluation of a novel (R)-4,4-difluoropiperidine scaffold as dopamine receptor 4 (D4R) antagonists

Herein, we report the synthesis and structure?activity relationship of a novel series of (R)-4,4-difluoropiperidine core scaffold as dopamine receptor 4 (D4) antagonists. A series of compounds from this scaffold are highly potent against the D4receptor and selective against the other dopamine receptors. In addition, we were able to confirm the active isomer as the (R)-enantiomer via an X-ray crystal structure.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

New explortion of 214894-89-0

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N-substituted nonaryl-heterocyclic NMDA/NR2B antagonists

Compounds represented by Formula (I): 1or pharmaceutically acceptable salts thereof, are effective as NMDA NR2B antagonists useful for relieving pain.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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3,3-DIFLUORO-PIPERIDINE DERIVATIVES AS NR2B NMDA RECEPTOR ANTAGONISTS

Disclosed are chemical entities of Formula (I): wherein X, Y, Z, R1, R3, R4 and R5 are defined herein, as NR2B subtype selective receptor antagonists. Also disclosed are pharmaceutical compositions comprising a chemical entity of Formula (I), and methods of treating various diseases and disorders associated with NR2B antagonism, e.g., diseases and disorders of the CNS, such as depression, by administering a chemical entity of Formula (I).

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

Some scientific research about 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine

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In heterogeneous catalysis, the catalyst is in a different phase from the reactants. Quality Control of 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 214894-89-0, name is 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine. In an article£¬Which mentioned a new discovery about 214894-89-0

Novel carbamate derivatives of 4-beta-amino-4?-O-demethyl-4- desoxypodophyllotoxin as inhibitors of topoisomerase II: Synthesis and biological evaluation

A novel series of carbamate derivatives of 4-beta-amino-4?-O- demethyl-4-desoxypodophyllotoxin were synthesized. Their effect on human DNA topoisomerase II and antiproliferative activity was evaluated. Compounds 4a-c, 4g, 4j and 4k are topoisomerase II poisons that induce double-stranded breaks in DNA and exhibit increased cytotoxicity compared to etoposide. The Royal Society of Chemistry 2005.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

Top Picks: new discover of 5-(Bromomethyl)-2,3-dihydro-1,4-benzodioxine

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Effect of O6-substituted guanine analogs on O6-methylguanine DNA-methyltransferase Expression and glioblastoma cells viability

Background: Glioblastoma multiforme (GBM) is often associated with a poor survival prognostic for patients. The main reason seems to be the acquired or inherent resistance to the chemotherapeutic agent used to treat the tumor, temozolomide (TMZ). To this day, the most recognized pathway of resistance is the DNA Direct Repair pathway by the means of the protein O6-methylguanine DNA-methyltransferase (MGMT). Objectives: To design and synthesize a series of MGMT inhibitors that can sensitize GBM cells to TMZ. Methods: Twenty-five O6-alkyl, O6-aryl and O6-substituted-aryl guanine analogs including nine novel compounds were synthesized, characterized, analyzed by molecular docking and tested on the T98G GBM cells viability. Results: Following molecular modeling with MGMT, the newly designed compounds 19, 22, and 24 emerged as the most promising MGMT ligands and displayed modest cytotoxicity. Guanine analog (19), bearing a p-nitrobenzyl moiety, reduced considerably the O6-methylguanine DNA-methyltransferase expression level. When combined with TMZ (1), which is used as first line treatment for brain tumors, compounds 19, 22, and 24 decreased T98G cellsoproliferation by 32%, 68% and 50%, respectively. TMZ (1) displayed negligible effect on the proliferation of these cells further supporting the notion that this cell model is resistant to this alkylating agent. Conclusion: Overall, these results notably highlight a group of MGMT inhibitors that warrants further exploration in the development of therapeutic options to circumvent TMZ resistance in brain tumors.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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CuBr2 catalyzed bromination/oxidation of isochromans to benzaldehyde derivatives

A series of isochromans were oxidized and brominated by using 1.2 equiv of CuBr2 in CH3CN at reflux to give the corresponding bromo benzaldehydes in moderate yields. A plausible mechanism for this transformation has been suggested.

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Reference£º
Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem