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Compounds based on the benzoxazine ring system STR1 are disclosed for use in enhancing synaptic responses mediated by AMPA receptors. The compounds are effective in the treatment of subjects suffering from impaired nervous or intellectual functioning due to deficiencies in the number or strength of excitatory synapses or in the number of AMPA receptors. The compounds can also be used for the treatment of non-impaired subjects for enhancing performance in sensory-motor and cognitive tasks which depend on brain networks utilizing AMPA receptors, for improving the performance of subjects with memory deficiencies, for treating schizophrenia, and for improving memory encoding.

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

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A series of 1-oxo-2-(3-piperidyl)-1,2,3,4-tetrahydroisoquinolines and related analogues were prepared and evaluated for their bradycardic activities in isolated right atrium and in anesthetized rats. (± )-6,7-Dimethoxy-2-{1- [3-(3,4-methylenedioxyphenoxy)propyl]-3-piperidyl}-1,2,3, 4-tetrahydroisoquinoline (4) was chosen as a lead, and structural modifications were performed on the tetrahydroisoquinoline ring and the terminal aromatic ring. The modifications on the tetrahydroisoquinoline ring revealed that the 1-oxo-1,2,3,4-tetrahydroisoquinoline ring system was optimum structure for both in vitro potency and in vivo efficacy. Furthermore, methoxy, ethoxy, and methoxycarbonyl groups were identified as preferable substituents on the terminal aromatic ring. One of the 1-oxo-1,2,3,4-tetrahydroisoquinoline derivatives, (R)-10a, was further evaluated for its bradycardic activity and inhibitory activity against If currents. Compound (R)-10a demonstrated potent bradycardic activity in rats with minimal influence on blood pressure after oral administration. The compound also showed inhibition of If currents (IC50 = 0.32 muM) in guinea pig pacemaker cells.

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

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Compounds based on the benzoxazine ring system that are remarkably more potent than corresponding benzoyl piperidines for enhancing synaptic responses mediated by AMPA receptors are disclosed, as are methods for the preparation thereof, and methods for their use for treatment of subjects suffering from impaired nervous or intellectual functioning due to deficiencies in the number of excitatory synapses or in the number of AMPA receptors. The invention compounds can also be used for the treatment of non-impaired subjects for enhancing performance in sensory-motor and cognitive tasks which depend on brain networks utilizing AMPA receptors and for improving memory encoding.

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

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The O-heterocycles, benzo-1,4-dioxane, phthalan, isochroman, 2,3-dihydrobenzofuran, benzofuran, and dibenzofuran are important building blocks with considerable medical application for the production of pharmaceuticals. Cytochrome P450 monooxygenase (P450) Bacillus megaterium 3 (BM3) wild type (WT) from Bacillus megaterium has low to no conversion of the six O-heterocycles. Screening of in-house libraries for active variants yielded P450 BM3 CM1 (R255P/P329H), which was subjected to directed evolution and site saturation mutagenesis of four positions. The latter led to the identification of position R255, which when introduced in the P450 BM3 WT, outperformed all other variants. The initial oxidation rate of nicotinamide adenine dinucleotide phosphate (NADPH) consumption increased ?140-fold (WT: 8.3 ± 1.3 min-1; R255L: 1168 ± 163 min-1), total turnover number (TTN) increased ?21-fold (WT: 40 ± 3; R255L: 860 ± 15), and coupling efficiency, ?2.9-fold (WT: 8.8 ± 0.1%; R255L: 25.7 ± 1.0%). Computational analysis showed that substitution R255L (distant from the heme-cofactor) does not have the salt bridge formed with D217 in WT, which introduces flexibility into the I-helix and leads to a heme rearrangement allowing for efficient hydroxylation.

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

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Process for preparing alkoxy- and aryloxy-phenols, comprising oxidizing the ketone of formula (I) with peracids to give the corresponding ester of formula (II) which is then hydrolysed to give the corresponding aryloxy- or alkoxy-phenol.

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

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We report the use of a rhodium(II) dimer in visible light photoredox catalysis for the aerobic oxidation of arylboronic acids to phenols under mild conditions. Spectroscopic and computational studies indicate that the catalyst Rh2(bpy)2(OAc)4 (1) undergoes metal-metal to ligand charge transfer upon visible light irradiation, which is responsible for catalytic activity. Further reactivity studies demonstrate that 1 is a general photoredox catalyst for diverse oxidation reactions.

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

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Methods of preparing carbamate prodrugs of amine-containing drugs are provided. Carbonates useful in the synthesis of the carbamate prodrugs are also provided.

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Benzodioxan,
1,4-Benzodioxane | C8H8O2 – PubChem

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The present invention relates to pyrimidine derivatives of formula (I) wherein (R1)n, R3, R4a, R4b, R5a, R5b and Ar1 are as described in the description and their use in the treatment of cancer by modulating an immune response comprising a reactivation of the immune system in the tumor. The invention further relates to novel benzofurane and benzothiophene derivatives of formula (II) and their use as pharmaceuticals, to their preparation, to pharmaceutically acceptable salts thereof, and to their use as pharmaceuticals, to pharmaceutical compositions containing one or more compounds of formula (I), and especially to their use as modulators of the prostaglandin 2 receptors EP2 and/or EP4.

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

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The vanilloid receptor-1 (VR1 or TRPV1) is a member of the transient receptor potential (TRP) family of ion channels and plays a role as an integrator of multiple pain-producing stimuli. From a high-throughput screening assay, measuring calcium uptake in TRPV1-expressing cells, we identified an N-aryl trans-cinnamide (AMG9810, compound 9) that acts as a potent TRPV1 antagonist. We have demonstrated the antihyperalgesic properties of 9 in vivo and have also reported the discovery of novel, orally bioavailable cinnamides derived from this lead. Herein, we expand our investigations and describe the synthesis and biological evaluation of a series of conformationally constrained analogues of the s-cis conformer of compound 9. These investigations resulted in the identification of 4-amino- and 4-oxopyrimidine cores as suitable isosteric replacements for the trans-acrylamide moiety. The best examples from this series, pyrimidines 79 and 74, were orally bioavailable and exhibited potent antagonism of both rat (IC50 = 4.5 and 0.6 nM, respectively) and human TRPV1 (IC50 = 7.4 and 3.7 nM, respectively). In addition, compound 74 was shown to be efficacious at blocking a TRPV1-mediated physiological response in vivo in the capsaicin-induced hypothermia model in rats; however, it was ineffective at preventing thermal hyperalgesia induced by complete Freund’s adjuvant in rats.

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

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The identification of a novel series of DprE1 inhibitors based on a 2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)-N-phenylpropanamide scaffold is described herein. SAR exploration around the HTS hit 1 led to the identification of multiple analogues with potent DprE1 inhibition and good whole-cell antimycobacterial activity.

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