- Intensely blue-fluorescent 2,5-bis(benzoimidazol-2-yl)pyrazine dyes with improved solubility: Their synthesis, fluorescent properties, and application as microenvironment polarity probes
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In order to improve the solubility of intensively fluorescent 2,5-bis(benzimidazol-2-yl)pyrazine (BBIP), we synthesized new BBIP derivatives (2, 3a,b, and 5a,b) possessing two alkyl chains at the N-1 and N-1′ positions of the two benzimidazole moieties. C
- Saito, Ryota,Matsumura, Yuriko,Suzuki, Saori,Okazaki, Naoki
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- Cell-Based Drug Discovery: Identification and Optimization of Small Molecules that Reduce c-MYC Protein Levels in Cells
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Elevated expression of the c-MYC oncogene is one of the most common abnormalities in human cancers. Unfortunately, efforts to identify pharmacological inhibitors that directly target MYC have not yet yielded a drug-like molecule due to the lack of any known small molecule binding pocket in the protein, which could be exploited to disrupt MYC function. We have recently described a strategy to target MYC indirectly, where a screening effort designed to identify compounds that can rapidly decrease endogenous c-MYC protein levels in a MYC-amplified cell line led to the discovery of a compound series that phenocopies c-MYC knockdown by siRNA. Herein, we describe our medicinal chemistry program that led to the discovery of potent, orally bioavailable c-MYC-reducing compounds. The development of a minimum pharmacophore model based on empirical structure activity relationship as well as the property-based approach used to modulate pharmacokinetics properties will be highlighted.
- Berrodin, Thomas J.,Bhaskar, Aishwarya,Brackley, James,Butticello, Michael,Carpenter, Christopher,Di Marco, Christina,Heerding, Dirk A.,Kallal, Lorena A.,Lafrance, Louis,Li, William H.,Mack, James F.,Mangatt, Biju,Martyr, Cuthbert,McHugh, Charles,Minthorn, Elisabeth,Nartey, Eldridge N.,Rivero, Ralph,Rubin, Jacob,Suarez, Dominic,Tian, Xinrong,Medina, Jesús R.
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p. 16056 - 16087
(2021/11/10)
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- Selenium-Catalyzed Carbonylative Synthesis of 2-Benzimidazolones from 2-Nitroanilines with TFBen as the CO Source
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A selenium-catalyzed carbonylative reaction for the synthesis of 2-benzimidazolones from 2-nitroanilines has been developed. In this strategy, to avoid the usage of toxic CO gas, TFBen (benzene-1,3,5-triyl triformate) was used as a solid and stable CO precursor, and a variety of desired 2-benzimidazolones were produced in moderate to excellent yields.
- Qi, Xinxin,Zhou, Rong,Peng, Jin-Bao,Ying, Jun,Wu, Xiao-Feng
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supporting information
p. 5161 - 5164
(2019/01/25)
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- A new series of N-substituted tetraphenylethene-based benzimidazoles: Aggregation-induced emission, fast-reversible mechanochromism and blue electroluminescence
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Four new N-substituted tetraphenylethene-based benzimidazoles N-R-2-(4-(1,2,2-triphenylvinyl)phenyl)-1H-benzo[d]imidazoles (R = phenyl (3a), R = 4-(tert-butyl)phenyl (3b), R = n-butyl (3c), R = n-hexyl (3d)) were synthesized conveniently by cyclization reaction of 4-tetraphenylenthenealdehyde with N-substituted ortho-nitroaniline. The four compounds exhibit typical aggregation-induced emission (AIE) property with relatively high solid state absolute fluorescence quantum yields (38.1–65.7%) and fast-recoverable mechanochromism property with solid-state fluorescence change between blue and yellow-green. They are thermally stable with decomposition temperatures above 319 °C. Both of multilayer electroluminescence devices fabricated with compounds 3b and 3c as emitters are blue emission. The turn-on voltage of device based on compound 3b is 3.3 V with maximum luminance and current efficiency of 2470 cd/m2 and 1.48 cd/A, respectively.
- Zhang, Tengfei,Zhang, Ran,Zhao, Yun,Ni, Zhonghai
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p. 276 - 285
(2017/09/20)
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- Chemoselective Deprotection of Sulfonamides under Acidic Conditions: Scope, Sulfonyl Group Migration, and Synthetic Applications
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Chemoselective acidic hydrolysis of sulfonamides with trifluoromethanesulfonic acid has been evaluated as a deprotection method and further extended to more complex synthetic applications. In contrast to conventional troublesome sulfonamide hydrolysis, a near-stoichiometric amount of acid was found to be sufficient to bring about efficient deprotection of various neutral or electron-deficient N-arylsulfonamides, whereas electron-rich substrates provided sulfonyl group migration products. The deprotection method developed is fully selective for N-arylsulfonamides, and the possibility to discriminate among various different sulfonamides is demonstrated.
- Javorskis, Tomas,Orentas, Edvinas
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p. 13423 - 13439
(2017/12/26)
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- Tetraphenylethylene-based blue light material containing benzimidazole unit as well as preparation method and application
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The invention discloses a tetraphenylethylene-based blue light material containing a benzimidazole unit. The tetraphenylethylene-based blue light material is shown as a structural formula I or II, wherein R1 is H, tert-butyl, n-butyl or hydroxyl, and R2 is alkyl. A 2-nitro-N-tert-butylphenyl amine or 2-nitro-N-n-butylphenyl amine precursor and a 4-formyl tetraphenylethylene precursor is firstly prepared, and then cyclization reaction is carried out to prepare a compound shown as the formula I or II. A preparation method of the compound is easy to operate, the reaction is moderate and the yield is high; the compound has relatively high decomposition temperature and glass-transition temperature, and shows blue fluorescence; the compound has a relatively good single-color property, so that an OLED (Organic Light Emitting Diode) device prepared by taking the compound as a luminescent material emits blue light; the starting voltage is 3.3V and the maximum brightness efficiency is 1.48cd/A. (The formula I and the formula II are shown in the description).
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Paragraph 0027; 0028; 0029; 0108; 0109
(2017/10/10)
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- Imidoyl dichlorides as new reagents for the rapid formation of 2-aminobenzimidazoles and related azoles
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The development of a reagent for the efficient synthesis of five- and six-membered azoles at room temperature is proposed. A variety of substituted 2-aminobenzimidazoles are synthesized in good to excellent yields. The ability to incorporate various protecting groups makes the imidoyl dichloride reagent amenable to a large number of syntheses. The reagent is applied to the total synthesis of the 2-aminobenzimidazole containing carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), from 2-chloro-3-nitropyridine in >60% yield in 6 steps.
- Pollock, Julie A.,Kim, Sung Hoon,Katzenellenbogen, John A.
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p. 6097 - 6099
(2015/10/28)
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- Discovery of isoalloxazine derivatives as a new class of potential anti-Alzheimer agents and their synthesis
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This article describes discovery of a novel and new class of cholinesterase inhibitors as potential therapeutics for Alzheimer's disease. A series of novel isoalloxazine derivatives were synthesized and biologically evaluated for their potential inhibitory outcome for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds exhibited high activity against both the enzymes AChE as well as BuChE. Of the synthesized compounds, the most potent isoalloxazine derivatives (7m and 7q) showed IC50 values of 4.72 μM and 5.22 μM respectively against AChE; and, 6.98 μM and 5.29 μM respectively against BuChE. These two compounds were further evaluated for their anti-aggregatory activity for β-amyloid (Aβ) in presence and absence of AChE by performing Thioflavin-T (ThT) assay and Congo red (CR) binding assay. In order to evaluate cytotoxic profile of these two potential compounds, cell viability assay of SH-SY5Y human neuroblastoma cells was performed. Further, to understand the binding behavior of these two compounds with AChE and BuChE enzymes, docking studies have been reported.
- Kanhed, Ashish M.,Sinha, Anshuman,Machhi, Jatin,Tripathi, Ashutosh,Parikh, Zalak S.,Pillai, Prakash P.,Giridhar, Rajani,Yadav, Mange Ram
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- Copper-mediated aryl amination: In situ generation of an active copper(I) species
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We have developed novel conditions for copper-mediated aryl amination by using a combination of easy-to-handle and inexpensive Cu(OAc) 2·H2O and phenylhydrazine. Georg Thieme Verlag Stuttgart . New York.
- Komori, Takashi,Satoh, Nobuhiro,Yokoshima, Satoshi,Fukuyama, Tohru
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experimental part
p. 1859 - 1862
(2011/09/15)
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- Synthesis of (alkylamino)nitroarenes by oxidative alkylamination of nitroarenes
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The viability of the oxidative alkylamination process for the derivatization of electron-deficient carboaromatics has been investigated. 1,3-Dinitrobenzene, 1-nitronaphthalene, and 1,5- and 1,8-dinitronaphthalenes have shown to react with a wide range of alkylamines in the presence of an oxidant (KMnO4, AgMnO4, AgPy2MnO4) to give access to the corre sponding N-alkyl-nitroarenamines in moderate to good yields. Nitroarenes are more reactive than azines towards alkylamines.
- Gulevskaya, Anna V.,Verbeeck, Stefan,Burov, Oleg N.,Meyers, Caroline,Korbukova, Inna N.,Herrebout, Wouter,Maes, Bert U. W.
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experimental part
p. 564 - 574
(2009/09/06)
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- QUINOXALINONE DERIVATIVES AS INSULIN SECRETION STIMULATORS, METHODS FOR OBTAINING THEM AND USE THEREOF FOR THE TREATMENT OF DIABETES
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The present invention relates to quinoxalinone derivatives of formula (I), wherein R1, R2, R3, R4, R5 and R6 are as defined in claim 1, as insulin secretion stimulators. The invention also relates to the preparation and use of these quinoxalinone derivatives for the prophylaxis and/or treatment of diabetes and pathologies associated. Other preferred compounds are compounds of general formula (I), wherein R1, R2, R3, R4, R5 and R6 can be optionally substituted by one or more groups selected from Z.
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Page/Page column 25
(2009/10/22)
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- Reactions of arenediazonium o-benzenedisulfonimides with aliphatic triorganoindium compounds
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The reaction of various arenediazonium o-benzenedisulfonimides with aliphatic triorganoindium compounds is described. Surprisingly, with triethyl- or tributylindium we obtained N-ethyl- or N-butylanilines, respectively. This is the first case in which, at least formally, the reactive site of a diazonium salt is the nitrogen atom directly bonded to the aromatic ring. In contrast, with trimethylindium we obtained only formaldehyde (aryl)hydrazones. In order to explain the difference between trimethyl- and triethylindium we have proposed some reaction mechanisms, supported by detailed density functional (DFT) calculations. The possible role of diazene/hydrazone tautomerism initially assumed was discarded and therefore three mechanisms for the key step (nucleophilic addition of the trialkylindium to the N=N double bond of diazene) were studied. For the favoured mechanism there is a difference in the energy barriers of 2 kcalmol-1 between the reactions with trimethyl- and triethylindium. This difference is explained on the basis of the different C-In bond energies in the two organometallics and it is assumed to be enough to explain their different behaviour under the experimental conditions. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Barbero, Margherita,Cadamuro, Silvano,Dughera, Stefano,Ghigo, Giovanni
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scheme or table
p. 862 - 868
(2009/04/11)
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- A mild inter- and intramolecular amination of aryl halides with a combination of CuI and CsOAc
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A unique combination of CuI and CsOAc was found to catalyze aryl amination under mild conditions. The reaction takes place at room temperature or at 90 °C with broad functional group compatibility. The intramolecular reaction was able to form five-, six-, and seven-membered rings with various protecting groups on the nitrogen atom. The scope of the intermolecular amination, as well as its applications to unsymmetrical N,N′-dialkylated phenylenediamines, was investigated.
- Kubo, Tetsuji,Katoh, Chiharu,Yamada, Ken,Okano, Kentaro,Tokuyama, Hidetoshi,Fukuyama, Tohru
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experimental part
p. 11230 - 11236
(2009/04/11)
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- Synthesis and structure of bifunctional N-alkylbenzimidazole phenylboronate derivatives
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N-Methyl and N-n-butyl-2-(2-boronophenyl)benzimidazoles are accessed from the corresponding mono-N-alkyl-ortho-phenylenediamines, either using a polyphosphoric acid-mediated cyclisation with ortho-bromobenzoic acid, or preferably using an Oxone-mediated c
- Blatch, Alexandrea J.,Chetina, Olga V.,Howard, Judith A.K.,Patrick, Leonard G.F.,Smethurst, Christian A.,Whiting, Andrew
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p. 3297 - 3302
(2008/09/17)
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- BIFUNCTIONAL CATALYSTS
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Bifunctional Lewis acid - Lewis base catalyst of Formula (I): wherein O is a C2-60 optionally heteroatom containing substituted or unsubstituted hydrocarbon scaffold comprising pendant or integral bifunctional groups LA and LB wherein LA is a pendant or integral boron or silicon Lewis acid group and LB is a pendant or integral phosphorus or nitrogen Lewis base group and its salts, N-fanctionalised derivatives, dimer or oligomer thereof; processes for the preparation thereof; novel compounds and novel intermediates; a composition comprising a catalyst or compound of the invention; a kit comprising one or more catalysts; the use thereof as catalysts in selective transformations, kits therefor and processes for selective transformation reactions catalysed thereby; screening methods to identify catalysts for specific transformations; and kits therefor.
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- Synthesis of Secondary Arylamines through Copper-Mediated Intermolecular Aryl Amination
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(Equation presented) A mild intermolecular copper-mediated amination of aryl iodides has been developed. The reaction takes place at room temperature or heating at 90°C and tolerates halogens attached to the aromatic ring. Its synthetic applications include a synthetic protocol for unsymmetrical N,N′-dialkylated phenylenediamines and both a stepwise and a general synthetic method for N-aryl secondary amines via Ns-anilides (readily obtained by reaction of the Ns-amide).
- Okano, Kentaro,Tokuyama, Hidetoshi,Fukuyama, Tohru
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p. 4987 - 4990
(2007/10/03)
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- Kinetics of the Reactions between 1,2-Dinitrobenzene and Aliphatic Primary Amines in Benzene. A Probable Mechanism for the Observed Mild Acceleration
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The kinetics of the aromatic nucleophilic substitution (SNAr) between 1,2-dinitrobenzene (1,2-DNB) and n- (BunNH2) and s-butylamine (BusNH2) have been investigated in benzene and hexane-benzene.The second-order rate coefficient for these reactions varies linearly with the amine concentration.However, the ratio of the slope and intercept of the straight lines (k''/k') are in the range for Bunnett's mild acceleration of unclear origin.This is in contrast to the genuine catalysis previously observed for the same reactions in n-hexane.The effect of additives such as pyridine, triethylamine, α-pyridone, and dimethyl sulphoxide was examined.It was found that the catalytic power of the additives qualitatively correlates with Kamlet-Taft's ?* and β parameters rather than with basicity constants of the additives in benzene.On other hand, when the steric requirements for the reactions of BusNH2 are compared with those for BunNH2, for the reaction with 1,2-DNB in benzene it seems that mild acceleration in benzene takes place for the decomposition of the SNAr intermediate.Studies of the reaction of 1,2-DNB with BunNH2 in hexane-benzene give good evidence that benzene forms an electron-donor-acceptor (EDA) complex with 1,2-DNB.It is concluded that, in pure benzene, 1,2-DNB is preferentially solvated by EDA complex formation and consequently the proximity effects either of the nucleophile or any additive will be quite different than in n-hexane.Hence benzene cannot be considered a typical non-polar inert solvent for SNAr reactions.
- Chiacchiera, Stella M.,Singh, Joaquin O.,Anunziata, Jorge D.,Silber, Juana J.
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p. 1585 - 1590
(2007/10/02)
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- Aromatic Nucleophilic Substitution Reactions of 1,2-Dinitrobenzene with Aliphatic Primary Amines in n-Hexane; Catalysis by Non-nucleophilic Bases
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The kinetics of the reactions of 1,2-dinitrobenzene with n-butyl-, s-butyl-, isobutyl-, n-propyl-, and isopropyl-amine in n-hexane at various temperatures have been investigated.The second-order rate coefficients for these reactions increase linearly with the amine concentrations.The values of the ratio of the rate constant for the catalysed process to the rate constant of the uncatalysed step 3RNH2/k2> are dependent on temperature, so that it is possible to minimize the catalysed or uncatalysed processes simply by temperature variation.Kinetic studies in the presence of non-nucleophilic bases confirmed the proposal that all these reactions are base-catalysed even for the cases where k3RNH2/k2 is less than 50.The role that electron donor-acceptor complex formation between reactants may play in the mechanism of these reactions is discussed.The influence of electronic and steric effects in the amine structure on the catalytic rate constant has been analysed.It has been shown that the catalysed step is disfavoured by electron-donating substituents and that it is inhibited by steric hindrance.The studies with the addition of the bulky bases TEA and TBA confirmed these conclusions.
- Chiacchiera, Stella M.,Singh, Joaquin O.,Anunziata, Jorge D.,Silber, Juana J.
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p. 987 - 994
(2007/10/02)
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- O- and N-Alkylsubstituted 2-(2'-Hydroxyphenyl)-benzimidazoles and -1,3,4-Oxadiazoles as Complexing and Extracting Agents for Copper-II-Ions
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2-(2'-Alkoxyphenyl)-benzimidazoles 1, 1-alkyl-2-(2'-hydroxyphenyl)-benzimidazoles 2, 2-(2'-hydroxy-4'-alkoxyphenyl)-benzimidazoles 3, 2-(2',4'-dialkoxyphenyl)-benzimidazoles 4 and 1-alkyl-2-(2'-hydroxy-5'-nitrophenyl)-benzimidazoles 7 are synthesized by condensation of 2-hydroxybenzoic acid derivatives and o-phenylendiamine or its derivatives.Alkyl chains (C4, C8 or C12) are introduced by alkylation before or after the ring closure in order to increase the solubility of the reagent in toluene or n-octane.Furthermore the extraction properties of the benzimidazoles are investigated.Also some new analogous compounds of the benzothiazole and the 1,3,4-oxadiazole series were synthesized.
- Beger, J.,Wagner, G.,Uhlig, E.,Dinjus, U.
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p. 708 - 718
(2007/10/02)
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