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ARYLOXY-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES

A glucokinase activator is provided; and a treatment and/or a preventive for diabetes, or a treatment and/or a preventive for diabetes such as retinopathy, nephropathy, neurosis, ischemic cardiopathy, arteriosclerosis, and further a treatment and/or a preventive for obesity are provided. The invention relates to a compound of a formula (I): [wherein R1 and R2 represent a hydrogen, etc.; R3 represents a hydrogen atom, a halogen atom, etc.; R4 each independently represents a hydrogen atom, a lower alkyl group, etc.; Q represents a carbon atom, a nitrogen atom or a sulfur atom (the sulfur atom may be mono- or di-substituted with an oxo group); R5 and R6 each represent a hydrogen atom, a lower alkyl group, etc.; X1, X2, X3 and X4 each independently represent a carbon atom or a nitrogen atom; Z represents an oxygen atom, a sulfur atom or a nitrogen atom; Ar represents an aryl or heteroaryl group optionally mono to tri-substituted with a group selected from the substituent group beta; ring A represents a 5- or 6-membered nitrogen-containing heteroaromatic group; m indicates an integer of from 1 to 6; n indicates an integer of from 0 to 3; p indicates an integer of from 0 to 2 (provided that at least two of X1 to X4 are carbon atoms); q indicates 0 or 1] or its pharmaceutically-acceptable salt, which has an effect of glucokinase activation and is useful as a treatment for diabetes.

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Oxazolidine – Wikipedia,
Oxazolidine | C3H114NO – PubChem

 

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Discovery of Novel DNA Gyrase Inhibiting Spiropyrimidinetriones: Benzisoxazole Fusion with N-Linked Oxazolidinone Substituents Leading to a Clinical Candidate (ETX0914)

A novel class of bacterial type-II topoisomerase inhibitor displaying a spiropyrimidinetrione architecture fused to a benzisoxazole scaffold shows potent activity against Gram-positive and fastidious Gram-negative bacteria. Here, we describe a series of N-linked oxazolidinone substituents on the benzisoxazole that improve upon the antibacterial activity of initially described compounds of the class, show favorable PK properties, and demonstrate efficacy in an in vivo Staphylococcus aureus infection model. Inhibition of the topoisomerases DNA gyrase and topoisomerase IV from both Gram-positive and a Gram-negative organisms was demonstrated. Compounds showed a clean in vitro toxicity profile, including no genotoxicity and no bone marrow toxicity at the highest evaluated concentrations or other issues that have been problematic for some fluoroquinolones. Compound 1u was identified for advancement into human clinical trials for treatment of uncomplicated gonorrhea based on a variety of beneficial attributes including the potent activity and the favorable safety profile.

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FUNGICIDAL COMPOSITIONS

A fungicidal composition comprising a mixture of components (A) and (B), wherein components (A) and (B) are as defined in claim 1, and use of the compositions in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.

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497-25-6, The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.497-25-6, Name is Oxazolidin-2-one, molecular formula is C3H5NO2. In a Article, authors is Song, Hai-Xia£¬once mentioned of 497-25-6

Concise and Additive-Free Click Reactions between Amines and CF3SO3CF3

Trifluoromethyl trifluoromethanesulfonate has proved to be an excellent reservoir of difluorophosgene and a promising click ligation for amines in the preparation of urea derivatives, heterocycles, and carbamoyl fluorides under metal- and additive-free conditions. The reactions are rapid, efficient, selective, and versatile, and can be performed in benign solvents, giving products in excellent yields with minimal efforts for purification. The characteristics of the reactions meet the requirements of a click reaction. The use of trifluoromethyl trifluoromethanesulfonate as a click reagent is advantageous over other ?CO? sources (e.g., TsOCF3, PhCO2CF3, CsOCF3, AgOCF3, and triphosgene) because this reagent is readily accessible; easy to scale up; and highly reactive, even under metal- and additive-free conditions. It is anticipated that CF3SO3CF3 will be increasingly as important as SO2F2 as a click agent in future drug design and development.

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497-25-6, A catalyst don’t appear in the overall stoichiometry of the reaction it catalyzes, but it must appear in at least one of the elementary reactions in the mechanism for the catalyzed reaction. 497-25-6, Name is Oxazolidin-2-one, molecular formula is C3H5NO2. In a Article, authors is Pal, Priyabrata£¬once mentioned of 497-25-6

Role of aqueous methyldiethanolamine (MDEA) as solvent in natural gas sweetening unit and process contaminants with probable reaction pathway

Aqueous methyldiethanolamine (MDEA) is used as a solvent in natural gas sweetening unit, whose quality deteriorates while absorbing H2S/CO2 causing corrosion and foaming in the process. Total process contaminants of lean MDEA obtained from GASCO Company (Habshan, Abu Dhabi) were determined using different instruments. The major hydrocarbons found in inlet natural gas was analyzed using gas chromatography mass spectrometry (GC-MS). Heat stable salt (HSS) anions and metal ions were detected using ion chromatograph (IC) and inductively coupled plasma optical emission spectrometry (ICP-OES). Liquid chromatography mass spectrometry (LC-MS) and direct sample analysis time of flight (AxION 2TOF) analysis were carried out to determine and major organic degraded products present in lean MDEA solvent. The UV-VIS spectrophotometer also justified the presence of total organic acid anions. Acetate and propionate were found to be present in higher amounts of 2806 and 1614ppm, respectively. Substantial amount of metal ions were also detected using ICP-OES with maximum level of heavy metal ions of lead and iron of 1.009 and 0.967ppm, respectively. Large numbers of organic degraded products such as diethanolamine followed by methylethanolamine, N,N-bis(2-hydroxyethyl) glycine (bicine) etc. were identified using LC-MS and AxION 2TOF analyses; which are considered to be major organic thermally degraded products. Thermal degradation experiment was compared with H2S and in presence of both H2S/CO2 to obtain same compounds with varying concentration. On the basis of MDEA degradation as reported by previous researchers and from the analyzed lean MDEA samples, probable reaction pathways have been proposed.

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Cyclic carbamates as reagents for alkylamination of aromatic derivatives under friedel-crafts conditions

Aryl(ethyl-) and propylamines are obtained with good yields by a decarboxylation-alkylation process applied on aluminium trichloride-cyclic carbamate complexes. The coupling of two aromatic units is observed in the case of oxazolidinonetoluene reaction.

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A rapid route to aminocyclopropanes via carbamatoorganozinc carbenoids

Easy as 1,2,3: Reaction of methyl carbamate, triethyl orthoformate, and readily available alkenes provides a highly practical preparation of protected aminocyclopropanes. The reaction proceeds with preferential cis addition to alkenes, and cleavage of the methyl carbamate gives the free aminocyclopropanes as their HI salts (see scheme).

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Any one of these steps may be slow and thus may serve as the rate determining step. In general, however, in the presence of the catalyst, the overall rate of the reaction is faster than it would be if the reactants were in the gas or liquid phase.

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Example 101 (R) and (S) -3- (5′-fluoro-2,2-dimethyl-2′-oxospiro [cyclopropane- 1 ,3′-hidoline] – 1 ‘-yl) -5- (2-oxooxazolidin-3-yl)benzoic acidSynthesis of methyl-3-bromo-5-(2-oxooxazolidin-3-yl)benzoateA suspension of 3-bromo-5-iodo-benzoic acid methyl ester (682 mg, 2 mmol), oxazolidin- 2-one (191 mg, 2.2 mmol), Cul (76 mg, 0.4 mmol), potassium carbonate (545mg, 4mmol) and N, N’-dimethyl-ethane-l,2-diamine (86uL, 0.8mmol) in acetonitrile (15 mL) was stirred for 16 hours at 90C. The precipitate was filtered off and washed with ethyl acetate. The filtrate was concentrated in vacuo to afford 3-bromo-5-(2-oxo-oxazolidin-3-yl)- benzoic acid methyl ester (480 mg, 80%) which was used for next step without further purification.

Any one of these steps may be slow and thus may serve as the rate determining step. In general, however, in the presence of the catalyst, the overall rate of the reaction is faster than it would be if the reactants were in the gas or liquid phase.

Reference£º
Patent; F. HOFFMANN-LA ROCHE AG; CHEN, Li; FENG, Lichun; HE, Yun; HUANG, Mengwei; YUN, Hongying; WO2011/70039; (2011); A1;,
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4-Fluoro-2-(2-oxooxazolidin-3-yl)benzonitrile. A 48 mL pressure vessel containing 2-bromo-4-fluorobenzonitrile (1.00 g, 5.00 mmol), 2-oxazolidone (0.390 g, 4.50 mmol), K2CO3 (0.970 g, 7.0 mmol) and xantphos (0.231 g, 0.40 mmol) in dioxane (10 mL) was degassed with argon for 15 inn. Pd2 dba3 (0.140 g, 0.15 mmol) was introduced and then the reaction mixture was heated at 70 C. for 18 h. The mixture was cooled, diluted with dioxane, and then filtered through Celite. The resulting mixture was concentrated in vacuo and subjected to column chromatography on silica gel with hexanes:ethyl acetate (1:1) to (3:7) gradient as the eluent to afford the title compound as a white solid (0.460 g, 50% yield): 1H NMR (400 MHz, CDCl3) delta ppm: 7.73 (1H, dd, J=5.8, 8.6 Hz), 7.43 (1H, dd, J=2.5, 9.6 Hz), 7.11 (1H, ddd, J=2.5, 7.5, 8.7 Hz), 4.60 (2H, t, J=7.1 Hz), 4.29 (2H, t, J=7.1 HJz); LCMS (+EST, M+H+) m/z 207.

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Reference£º
Patent; Bristol-Myers Squibb Company; US2007/129379; (2007); A1;,
Oxazolidine – Wikipedia
Oxazolidine | C3H7NO – PubChem

 

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General procedure: In a 250 cm3 two-neck round-bottom flask equipped with astir-bar, CuCl2(0.2 equiv.), nitrogen nucleophile (5 equiv.),and Na2CO3(2 equiv.) were combined. The reaction flask was purged with oxygen gas. A solution of pyridine(2 equiv.) in dry toluene (0.06 M) was added to the reactionflask and stirred at 70 C. After 0.5 h, a solution ofthe respective alkyne (1.0 equiv.) in dry toluene (0.033 M)was added to the flask over 4 h using a syringe pump. Afteraddition of alkyne/toluene solution, the reaction mixture wasallowed to stir at 70 C overnight. After cooling to r.t., thecrude mixture was concentrated under reduced pressure. Theresidue was purified by column chromatography on silicagel.

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Reference£º
Article; Brutiu, Bogdan R.; Bubeneck, Wilhelm Andrei; Cvetkovic, Olivera; Li, Jing; Maulide, Nuno; Monatshefte fur Chemie; vol. 150; 1; (2019); p. 3 – 10;,
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