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Neutral sphingomyelinase 2 (nSMase2), a key enzyme in ceramide biosynthesis, is a new therapeutic target for the treatment of neurological disorders and cancer. Using 2,6-dimethoxy-4-[4-phenyl-5-(2-thienyl)-1H-imidazol-2-yl]phenol (DPTIP), our initial hit compound (IC50 = 30 nM) from nSMase2 screening efforts, as a molecular template, a series of 4-(1H-imidazol-2-yl)-2,6-dialkoxyphenol derivatives were designed, synthesized, and evaluated. Systematic examination of various regions of DPTIP identified the key pharmacophore required for potent nSMase2 inhibition as well as a number of compounds with the 4-(1H-imidazol-2-yl)-2,6-dialkoxyphenol scaffold with similar or higher inhibitory potency against nSMase2 as compared to DPTIP. Among them, 4-(4,5-diisopropyl-1H-imidazol-2-yl)-2,6-dimethoxyphenol (25b) was found to be metabolically stable against P450 metabolism in liver microsomes and displayed higher plasma exposure following oral administration as compared to DPTIP. Analysis of plasma samples identified an O-glucuronide as the major metabolite. Blockade of the phase II metabolism should further facilitate our efforts to identify potent nSMase2 inhibitors with desirable ADME properties.

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The dynamic chemical diversity of the numerous elements, ions and molecules that constitute the basis of life provides wide challenges and opportunities for research. 92420-89-8, Name is (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate, molecular formula is C15H18Cl3NO10. In a Article,once mentioned of 92420-89-8, Related Products of 92420-89-8

We demonstrate that an extended scaffold based on a self-immolative linker (SIL) enables the universal production of O-aryl glucuronide prodrugs: high yield glucuronidation is performed on a precursor substrate (SIL) and the subsequent drug conjugation proceeds via less challenging chemical reactions.

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Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data.name: (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 92420-89-8, in my other articles.

name: (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate, Children learn through play, and they learn more than adults might expect. Science experiments are a great way to spark their curiosity, get their minds active, and encourage them to do something that doesn’t involve a screen. An article , which mentions 92420-89-8, molecular formula is C15H18Cl3NO10. The compound – (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate played an important role in people’s production and life.

Acolbifene (EM-652·HCl, SCH 57068·HCl), a highly potent and orally active selective estrogen receptor modulator (SERM), is at late stage clinical development for the treatment of estrogen-sensitive breast cancer. Acolbifene-7-glucuronide 1 (major) and acolbifene-4?-glucuronide 2 (minor) were identified as metabolites of acolbifene in the human. The two monoglucuronides and a diglucuronide 3 as well as the corresponding 2H-labelled derivatives 4-6 were synthesised for use as preclinical and clinical standards for LC-MS/MS analysis. All glucuronides were prepared by the Schmidt glycosylation of monoprotected acolbifene with a glucuronyl imidate at – 10C to prevent epimerisation at the C-2 position. The two monoglucuronides 1 and 2 of acolbifene were separated by semi-preparative HPLC. Incorporation of three deuteriums was achieved by alkylation of chromanone 15 with C2H3MgI followed by dehydration with C 2H3CO2 2H/2H 2O. After chemical resolution and salt neutralisation, [ 2H3]acolbifene 19 was obtained with 99.4% enantiomeric purity and >98% isotopic purity. Copyright

Sometimes chemists are able to propose two or more mechanisms that are consistent with the available data.name: (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate, If a proposed mechanism predicts the wrong experimental rate law, however, the mechanism must be incorrect.Welcome to check out more blogs about 92420-89-8, in my other articles.

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Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.Quality Control of: (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate. In my other articles, you can also check out more blogs about 92420-89-8

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Giving cholesterol the brush off: An intestinal brush border membrane vesicle assay has been devised for the convenient in vitro testing of small molecules for inhibition of cholesterol absorption. The assay was used to identify new nonhydrolyzable glycosides as potent cholesterol-absorption inhibitors and an oxazolidinone as an effective replacement of the beta-lactam scaffold of ezetimibe (1).

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Recommanded Product: (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate, Chemical engineers work across a number of sectors, processes differ within each of these areas, are directly involved in the design, development, creation and manufacturing process of chemical products and materials. An article , which mentions 92420-89-8, molecular formula is C15H18Cl3NO10. The compound – (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate played an important role in people’s production and life.

A variety of hydroxylic aglycones can be glucuronidated directly with methyl 2,3,4-tri-O-acetylglucopyranuronate (4a), activated with trimethylsilyl trifluoromethanesulfonate (Me3Si-OTf).This reaction provides mostly beta, and sometimes alpha, glucopyranosiduronic acid derivatives (referred to as glucuronides) rapidly and at low temperatures.The epimeric ratio depends on the relative aglycone nucleophilicity vs. its tendency to form a stabilized carbocation by the formal loss of -OH.Glucuronides of various aromatic and aliphatic aglycones as well as those of a number of cyanohydrins were prepared.The characteristic features of the 1H NMR spectra of alpha and beta derivatives which are presented are useful in the assignment of product stereochemistry and determination of epimeric ratios in those reactions where mixtures are obtained.

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Quality Control of: (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate, The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature 92420-89-8, C15H18Cl3NO10. A document type is Article, introducing its new discovery.

This work describes our preliminary efforts towards the development of aryl glucuronides as potential probes for heparanase. During the course of these initial investigations, attempted glycosidation of methyl 2,3,4-tri-O-acetyl- alpha-d-glucopyranosyluronate trichloroacetimidate with 4-hydroxycinnamic acid gave a complex mixture of four different components. These were identified as the 1-cinnamyl glucuronate ester 13, the cinnamyl linked disaccharide 14, the glucuronate trichloroacetamide 15, and the glucuronyl alpha-fluoride 16. This paper rationalises the formation of each of these products, and reports our efforts in trying to optimise the formation of the alpha-fluoride 16.

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Chemistry can be defined as the study of matter and the changes it undergoes. You’ll sometimes hear it called the central science because it is the connection between physics and all the other sciences, starting with biology. 92420-89-8, Name is (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate, molecular formula is C15H18Cl3NO10. In a Article,once mentioned of 92420-89-8, Safety of (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate

Compounds that alter endothelial cell growth are of interest in the development of angiogenesis modulators. A structurally diverse series of saccharide derivatives (glycosylamide conjugates) have been synthesized and evaluated for their effects on bovine aortic endothelial cell (BAEC) growth. Heparin-albumin (HA) reduced BAEC growth by 32% at 10mug/mL and a number of the novel saccharide conjugates from the library were found to mimic the effect of HA as they also inhibit endothelial cell survival under identical conditions. Two thiophene conjugates, thioglucamide (24% inhibition at 35muM) and a related glucuronide (26% inhibition at 33muM) were the most potent inhibitors of BAEC growth, as determined using a methylthiazol tetrazolium (MTT) assay. The effects of thioglucamide and HA on absolute cell number were also studied using cell counting experiments; thioglucamide (47% after 24h) was more potent than indicated by the MTT assay and initially reduced the BAEC number to a greater extent than HA (30% after 24h); however, its actions were over more rapidly than were HA’s as cell growth had returned to levels of the control after 72h where HA still caused 25% inhibition. The binding of the monosaccharide conjugates to fibroblast growth factor (FGF-2) in competition with heparin-albumin by ELISA was investigated to establish the possible mechanism by which glycoconjugates could alter growth but there was no general correlation between reduction in viable cell population and binding to FGF-2. No glycoconjugate reduced the proliferation of mouse mammary epithelial cells, nor did any alter gross cell morphology, supporting a proposal that the reduction in BAEC survival by monosaccharide conjugates such as thioglucamide is a result of the inhibition of cell proliferation rather than being an induction of cytotoxicity. These studies indicate that cell biological studies to determine the mechanism of action of the simple monosaccharide conjugates may be worthwhile.

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Chemotherapy of malign tumors is usually associated with serious side effects as common anticancer drugs lack selectivity. An approach to deal with this problem is the antibody-directed enzyme prodrug therapy (ADEPT) and the prodrug monotherapy (PMT). Herein, the synthesis and biological evaluation of new glycosidic prodrugs suitable for both concepts are described. All prodrugs but one are stable in human serum and show QIC50 values (IC 50 of prodrug/IC50 of prodrug in the presence of the appropriate glycohydrolase) of up to 6500. This is the best value found so far for compounds interacting with DNA.

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The polymorphism of the glycoside donor methyl 2,3,4-tri-O-acetyl-1-O- (trichloroacetimidoyl)-alpha-d-glucopyranouronate (1) has been investigated. Two polymorphic forms (labelled Forms I and II) have been elucidated and fully characterised by DSC, PXRD and single crystal analysis, both crystallizing in the space group P21. Form I was obtained by crystallization from a wide range of solvents, while Form II was obtained only from ethyl acetate or isopropanol on certain occasions. Unit cell dimensions for Form I are a 14.0292(12), b 8.9641(8), c 16.8580(14) A, beta 94.285(2), and for Form II a 11.266(3), b 6.8889(17), c 13.921(4) A, beta 101.161(6). Z’ is 2 for Form I and 1 for Form II. Form I displays two moderate intermolecular hydrogen bonds in the unit cell whereas Form II shows no moderate hydrogen-bonding motifs. All three molecules in the two polymorphs differ significantly in their conformations, especially with respect to the methyl carboxylate and trichloroacetimidoyl groups.

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Balanced chemical reaction does not necessarily reveal either the individual elementary reactions by which a reaction occurs or its rate law.COA of Formula: C15H18Cl3NO10. In my other articles, you can also check out more blogs about 92420-89-8

Chemistry is an experimental science, and the best way to enjoy it and learn about it is performing experiments.Introducing a new discovery about 92420-89-8, Name is (2S,3S,4S,5R,6R)-2-(Methoxycarbonyl)-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate, COA of Formula: C15H18Cl3NO10.

The conjugation of carbohydrates to synthetic scaffolds has the goal of preparing potent inhibitors of lectin binding. We herein report the synthesis of a panel of bivalent compounds (cyclophane and terephthalamide-derivatives) then used to establish the influence of scaffold flexibility on respective inhibitory potency in a medically relevant test system. Synthetic routes to two phenylenediamine-based glycocyclophanes involving Ugi reactions of glucuronic acid derivatives and subsequent ring closing metathesis are described, as are improvements for producing terephthalamide-based carbohydrate carriers. Assays were performed with human tumour cells measuring quantitatively the influence of the test compounds on fluorescent surface staining by labelled lectins. Biological evaluation using two different lines of cancer cells as well as cells with known alterations in the glycomic profile (cells treated with an inhibitor of glycan processing and a glycosylation mutant) reduced the risk of generating premature generalizations regarding inhibitor potency. Bioactivity relative to free mannose was invariably determined for the synthetic compounds. A clear trend for enhanced inhibitory properties for macrocyclic compounds compared to non-macrocyclic derivatives was discerned for one type of glycocyclophane. Herein we also document the impact of altering the spacing between the mannose residues, altering cell surface ligand density and cell-type reactivity. The applied strategy for the cell assays is proposed to be of general importance in the quest to identify medically relevant lectin inhibitors.

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Reference:
Tetrahydropyran – Wikipedia,
Tetrahydropyran – an overview | ScienceDirect Topics