- Synthesis of tetrazoles, triazoles, and imidazolines catalyzed by magnetic silica spheres grafted acid
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The magnetically separable catalysts are used in the synthesis of N-containing heterocycles, including tetrazoles, triazoles, and imidazolines. The magnetic silica sphere grafted sulfonic acid (MSS-SO3H) is suitable for the synthesis of 1,2,3-triazole via the cycloaddition of nitroalkene with NaN3, whereas the zinc-modified silica sphere catalyst (MSS-SO3Zn) is more suitable for the synthesis of tetrazoles. The MSS-SO3Zn catalyst also works well for the synthesis of 2-substituted imidazoline via the condensation of nitriles with ethylenediamine. Both of the MSS-SO3H and MSS-SO3Zn catalysts can be recovered easily by a magnet, and they can be reused without further tedious activation.
- Jiang, Ruihang,Sun, Hong-Bin,Li, Shuang,Zhan, Kun,Zhou, Junjie,Liu, Lei,Zhang, Kai,Liang, Qionglin,Chen, Zhangpei
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supporting information
p. 2652 - 2662
(2018/11/26)
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- Semi-empirical computation on mechanism of imidazolines and benzimidazoles synthesis and their QSAR studies
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A green, mild and anaerobic synthesis of imidazolines and benzimidazoles from aldehydes and diamines using I2/KI/K2CO3/H2O system has been investigated by semi-empirical methods. The observed efficient direction of the above synthesis has been modeled from a comparison of the energies of four possible transition states arising from mono and di additions of iodines in the configured molecules. In the reaction I1 B is the most favorable transition state [TS] which is shown to be 20 Kcal/mol by PM3 analyses. The resulting trends of relative transition states energies are in excellent agreement with the experimental observations. Also, the bond order, bond length, heat of formation is in good agreement to the formation of product B. In order to establish the suitable mechanism of the reaction a quantitative structure activity relationship analysis has been made using hydrophobicity as the molecular descriptor. In this analysis the values of refractivity, polarizability, hydration energy, electron affinity, ionization potential and dipole moment of the compounds have been correlated with their hydrophobicity which has been taken as the molecular property.
- Hazarika, Swapnali,Konwar, Dilip,Bora, Manas Jyoti
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p. 5073 - 5078
(2015/01/09)
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- Optimisation of imidazole compounds as selective TAAR1 agonists: Discovery of RO5073012
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A series of imidazole compounds has been identified which affords potent and selective partial and full agonists of the TAAR1 receptor. Starting from 2-benzyl-imidazoline screening hits, a series of structurally related 2-benzyl- and 4-benzyl-imidazoles was investigated first, but it proved highly challenging to obtain compounds having sufficient selectivity against the adrenergic alpha 2 receptor. This issue could be successfully addressed by modification of the linker region and SAR exploration led to the discovery of highly selective isopropyl-substituted 4-aminomethyl-imidazole compounds. The work culminated in the identification of the selective TAAR1 partial agonist RO5073012 (4-chlorophenyl)-(1H-imidazol-4-ylmethyl)-isopropyl-amine, 24), which has a good pharmacokinetic profile after oral administration in rodents. RO5073012 has been found to be active in a behavioural rat model which is considered indicative for schizophrenia.
- Galley, Guido,Stalder, Henri,Goergler, Annick,Hoener, Marius C.,Norcross, Roger D.
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supporting information; experimental part
p. 5244 - 5248
(2012/09/07)
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- CuCl-catalyzed radical cyclisation of N-α-perchloroacyl-ketene-N,S- acetals: A new way to prepare disubstituted maleic anhydrides
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The copper-catalyzed radical cyclization (RC) of N-α-perchloroacyl cyclic ketene-N,X(X=O, NR, S)-acetals was studied. While the RC of N-acyl ketene-N,O-acetals was unsuccessful, the 5-endo cyclization of the other ketene acetals provided much better results, with the following order of cyclization efficiency: hexa-atomic cyclic ketene-N,NR-acetalspenta-atomic cyclic ketene-N,S-acetalshexa-atomic cyclic ketene-N,S-acetals. Invariably the catalytic cycle begins with the formation of a carbamoyl methyl radical. This leads to a cascade of reactions, including a radical polar crossover step, which ends with the formation of the maleimide nucleus, or precursors of this. Products from the RC of the hexa-atomic cyclic ketene-N,S-acetals, were efficiently transformed into disubstituted maleic anhydrides.
- Cornia, Andrea,Felluga, Fulvia,Frenna, Vincenzo,Ghelfi, Franco,Parsons, Andrew F.,Pattarozzi, Mariella,Roncaglia, Fabrizio,Spinelli, Domenico
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experimental part
p. 5863 - 5881
(2012/09/22)
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- THERAPY FOR COMPLICATIONS OF DIABETES
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A method for enhancing glycemic control and/or insulin sensitivity in a human subject having diabetic nephropathy and/or metabolic syndrome comprises administering to the subject a selective endothelin A (ETA) receptor antagonist in a glycemic control and/or insulin sensitivity enhancing effective amount. A method for treating a complex of comorbidities in an elderly diabetic human subject comprises administering to the subject a selective ETA receptor antagonist in combination or as adjunctive therapy with at least one additional agent that is (i) other than a selective ETA receptor antagonist and (ii) effective in treatment of diabetes and/or at least one of said comorbidities other than hypertension. A therapeutic combination useful in such a method comprises a selective ETA receptor antagonist and at least one antidiabetic, anti-obesity or antidyslipidemic agent other than a selective ETA receptor antagonist.
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- ANTIHYPERTENSIVE THERAPY
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A new use of darusentan is provided in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy with one or more drugs. The composition comprises darusentan in an amount providing a therapeutically effective daily dose; wherein (a) the composition is orally deliverable and/or (b) the daily dose of darusentan is effective to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures. Further provided is a new use of darusentan in preparation of a pharmaceutical composition for lowering blood pressure in a patient exhibiting resistance to a baseline antihypertensive therapy, wherein the composition is administered adjunctively with at least one diuretic and at least one antihypertensive drug selected from ACE inhibitors, angiotensin II receptor blockers, beta-adrenergic receptor blockers and calcium channel blockers.
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- N-nitrosotolazoline: Decomposition studies of a typical N-nitrosoimidazoline
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N-Nitrosotolazoline (N-nitroso-2-benzylimidazoline), a N-nitrosated drug typical of N-nitrosoimidazolines, reacts readily with aqueous acid, nitrous acid, or N-acetylcysteine to produce highly electrophilic diazonium ions capable of alkylating cellular nucleophiles. The kinetics and mechanism of the acidic hydrolytic decomposition of N-nitrosotolazoline have been determined in mineral acids and buffers. The mechanism of decomposition in acidic buffer is proposed to involve the rapid reversible protonation of the imino nitrogen atom followed by slow general base-catalyzed addition of H2O to the 2-carbon of the imidazoline ring to give a tetrahedral intermediate, which is also a α-hydroxynitrosamine. Rapid decomposition of this species gives rise to the diazonium from which the products are derived by nucleophilic attack, elimination, and rearrangement. The proposed mechanism is supported by the observations of general acid catalysis, a negligible deuterium solvent kinetic isotope effect (kH/kD - 1.15) and ΔS≠ = -34 eu. In phosphate buffer at 30°C, the half-lives of N-nitrosotolazoline range from 5 min at pH 3.5 to 4 h at pH 6. The main reaction product of the hydrolytic decomposition is N-(2-hydroxyethyl)phenylacetamide. This and other products are consistent with the formation of a reactive diazonium ion intermediate. N-Nitrosotolazoline nitrosates 50 times more rapidly than tolazoline and results in a set of products derived from reactive diazonium ions but different from those produced from the hydrolytic decomposition of the substrate. N-Acetylcysteine increases the decomposition rate of N-nitrosotolazoline by 25 times at pH 7 and results in both N-denitrosation and induced decomposition to produce electrophiles. These data suggest that N-nitrosotolazoline shares the chemical properties of many known direct-acting mutagens and carcinogens.
- Loeppky, Richard N.,Shi, Jianzheng
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p. 308 - 318
(2008/12/22)
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- Method for treating resistant hypertension
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A method is provided for lowering blood pressure in a patient having clinically diagnosed resistant hypertension. The method comprises administering darusentan to the patient adjunctively with a baseline antihypertensive regimen that comprises administration of at least one diuretic and at least two antihypertensive drugs selected from at least two of (a) ACE inhibitors and angiotensin II receptor blockers, (b) beta-adrenergic receptor blockers and (c) calcium channel blockers. The darusentan is orally administered at a dose and frequency effective, in combination with the baseline regimen, to provide a reduction of at least about 3 mmHg in one or more blood pressure parameters selected from trough sitting systolic, trough sitting diastolic, 24-hour ambulatory systolic, 24-hour ambulatory diastolic, maximum diurnal systolic and maximum diurnal diastolic blood pressures.
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- An efficient preparation of 2-imidazolines and imidazoles from aldehydes with molecular iodine and (diacetoxyiodo)benzene
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2-Imidazolines were easily prepared in quite good yields from the reaction of aldehydes and ethylenediamine with molecular iodine in the presence of potassium carbonate. Moreover, 2-imidazolines obtained were smoothly oxidized to the corresponding imidazoles in good yields using (diacetoxyiodo)benzene at room temperature. Georg Thieme Verlag Stuttgart.
- Ishihara, Midori,Togo, Hideo
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p. 227 - 230
(2007/10/03)
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- An efficient and one-pot synthesis of imidazolines and benzimidazoles via anaerobic oxidation of carbon-nitrogen bonds in water
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The system, I2/KI/K2CO3/H2O, oxidizes carbon-nitrogen bonds for the synthesis of imidazolines and benzimidazoles from aldehydes and diamines under anaerobic conditions in water at 90°C with excellent yields. The process is green, mild and inexpensive.
- Gogoi, Pranjal,Konwar, Dilip
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- Zeolite-catalyzed simple synthesis of different heterocyclic rings, part 2
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A simple and environmentally friendly synthesis was developed for the preparation of 2-arylimidazoline derivatives and 2-arylbenzoxazole derivatives using a small pore size zeolite. The similar reaction was not applicable to the preparation of the sulfur-containing analogs cysteamine or 2-aminothiophenol, probably because of a disadvantageous reaction between the zeolite and the thio compound.
- Hegedues, Adrienn,Vigh, Ilona,Hell, Zoltan
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p. 428 - 431
(2007/10/03)
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- A novel synthetic method for 2-arylmethyl substituted imidazolines and imidazoles from 2-aryl-1,1-dibromoethenes
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Various 2-arylmethylimidazolines were prepared by treating readily available 2-aryl-1,1-dibromoethenes with ethylenediamine under mild conditions and further converted into the corresponding imidazoles smoothly with Swern oxidation. Graphical Abstract
- Huh, Dal Ho,Ryu, Hoejin,Kim, Young Gyu
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p. 9857 - 9862
(2007/10/03)
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- New one-step synthesis of 2-aryl-1H-imidazoles: Dehydrogenation of 2-aryl-δ2-imidazolines with dimethylsulfoxide
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A new one-step method for the preparation of 2-aryl-1Himidazoles 3, based on the DMSO dehydrogenation of 2-aryl-Δ2-imidazolines, is described. A comparative study between DMSO and 10% Pd/C, the best known catalyst employed in this transformation, has also been developed. Both protocols were carried out at 120 °C for 48 hours.
- Anastassiadou,Baziard-Mouysset,Payard
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p. 1814 - 1816
(2007/10/03)
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- Synthesis of aldehydes from carboxylic acids via 2-imidazolines
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The use of readily available 2-substituted-2-imidazolines as precursors to 2-hydroxy aldehyde, unsaturated aldehyde and a variety of functionalized aldehydes is reported. It provides a novel method for the preparation of aldehydes from carboxylic acids via 2-substituted-2-imidazolines.
- Shi, Zhen,Gu, Huan
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p. 2701 - 2707
(2007/10/03)
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- 1-(Phenylethynyl)aziridine in reactions with amines
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The reaction of 1-(phenylethynyl)aziridine with a primary or secondary amine gave 2-benzylimidazoline-2 or N-aminoethyl substituted phenylacetamidine via nucleophilic attack on the aziridine ring. The mechanism of aziridine ring opening by an amine was studied.
- Tikhomirov,Porchinskaya,Eremeev
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p. 498 - 501
(2007/10/02)
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