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The versatility and potential of a norcoclaurine synthase (NCS) from Coptis japonica NCS2 has been investigated, together with the development and application of a novel fluorescence-based high-throughput assay using nearly forty amines/aldehydes. The stereocontrol exerted by CjNCS2 on selected non-natural substrates has been determined, where the tetrahydroisoquinolines (THIAs) were formed as the (1S)-isomer in >95% ee, as observed with the natural product norcoclaurine. Docking calculations involving THIA mechanism intermediates, utilising the reported Thalictrum flavum NCS X-ray crystallographic structure, were carried out and combined with the CjNCS2 screening results to further understand the mode of action of NCS. These findings suggested that in addition to the key active-site residues K122 and E110, D141 is also mechanistically essential for the enzymatic transformation. The exceptional tolerance of NCS towards aldehyde substrates is furthermore supported by our proposed mechanism in which the aldehydes protrude out of the enzymatic pocket. Copyright

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

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

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An efficient copper-TEMPO-catalyzed one-pot synthesis of alpha-ketoamides from phenethyl alcohol derivatives was developed firstly. Moreover, molecular oxygen in open air was employed as the oxidant with a broad substrate scope, which makes this methodology more practical. Based on some control experiments, a plausible mechanism was proposed.

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

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The synthesis of a series of novel 4-substituted 2,3,6,7-tetrahydrobenzo [1,2-b;4,5-b?]difuran?1H-imidazolium salts is presented. The biological properties of the compounds were evaluated in vitro against a panel of human tumor cell lines. Results suggest that the 5,6-dimethyl-benzimidazole or 2-methyl-benzimidazole ring, and substitution of the imidazolyl-3-position with a 2-naphthylmethyl substituent or 2-naphthylacyl substituent, were important to the cytotoxic activity. Notably, 3-(2-Naphthylmethyl)-1-((2,3,6,7-tetrahydrobenzo[1,2-b;4,5-b?]difuran-4-yl)methyl)-1H-5,6-dimethyl-benzimidazol-3-ium bromide (42) was found to be the most potent derivative against five human tumor cell lines with IC50 values of 1.06?4.34 muM and more selective towards SMMC-7721, A549 and SW480 cell lines. 3-(2-Naphthylacyl)-1-((2,3,6,7-tetrahydrobenzo[1,2-b;4,5-b?]difuran-4-yl)methyl)-1H-2-methyl-benzimidazol-3-ium bromide (37) showed higher selectivity to SMMC-7721 and MCF-7 cell lines with IC50 values 2.7-fold and 8.4-fold lower than DDP. Study regarding to the antitumor mechanism of action showed that compound 37 could induce cell cycle G1 phase arrest and apoptosis in SMMC-7721 cells.

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

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Two compounds, obtained by random screening, and displaying micromolar activities on the mu opiate receptor were used as starting points for optimization. In that work, the traditional concept of the activity of a compound (related to one or a few targets) was extended to the comprehensive pharmacological profile of that compound on more than 70 receptors, transporters, and channels relevant to a CNS-oriented project. Using the two complementary design strategies based on two similarity concepts described in the previous paper, we have obtained analogues with IC50 values ranging between 0.9 nM and a few micromolar on the mu receptor and displaying qualitatively different profiles. We discuss here, both on a case-by-case basis and from a statistical standpoint, the pharmacological profiles in light of the two similarity concepts.

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

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A compound of formula I, including optical isomers thereof, STR1 wherein X represents –SO 2 NH– or –NHSO 2 –,p, q and r independently represent 2 or 3,Y represents thienyl optionally substituted by alkyl or halogen, or phenylthio- or phenyl optionally substituted by alkyl or halogen, andeach R independently represents H or alkyl,and pharmaceutically acceptable salts, esters and amides thereof.

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

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A series of 4-substituted phenoxypropanolamines was prepared and examined for beta-adrenoceptor activity.Some of the compounds, especially the <4-<2-<<2-(4-fluorophenyl)ethyl>oxy>ethoxy>phenoxy>propanolamines (14, 15, and 24), showed potent beta1-blockade with virtually no beta2-blockade at doses over a 1000 times greater.The compounds also possessed partial agonist activity.Structure-activity relationships are discussed, and conclusions are drawn about the binding sites on beta-adrenoceptors.

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

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The present invention provides various processes for the preparation of (R)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemethanol. These processes may be characterized by the following scheme: 1

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

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A process for fluorination of aromatic compounds employing iodonium ylides and applicable to radiofluorination using 18F is described. Processes, intermediates, reagents and radiolabelled compounds are described.

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

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The disclosure provides a dual-catalysis system for direct conversion of olefins to alcohols. The cooperative catalytic system contains one oxidizing catalyst and one transfer-hydrogenation catalyst. A wide variety of olefins, including aromatic and aliphatic olefins, can be used as the reactant. The transformation proceeds with anti-Markovnikov selectivity, and in some aspects provides primary alcohols as major products. The disclosure further provides a system for oxidation of olefins with anti-Markovnikov selectivity.

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