- A new insight into the push-pull effect of substituents via the stilbene-like model compounds
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In this paper, authors report on 1-pyridyl-2-arylethenes, 1-furyl-2-arylethylenes, 1,2-diphenylpropylenes and substituted cinnamyl anilines as stilbene-like model compounds to investigate the factors dominating the push-pull effect of substituents via usi
- Cao, Chaotun,Cao, Chenzhong,Zeng, Zhao
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- Determination and application of the excited-state substituent constants of pyridyl and substituted phenyl groups
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Thirty six 1-pyridyl-2-arylethenes XCH=CHArY (abbreviated XAEY) were synthesized, in which, X is 2-pyridyl, 3-pyridyl and 4-pyridyl and Y is OMe, Me, H, Br, Cl, F, CF3, and CN. Their ultraviolet absorption spectra were measured in anhydrous ethanol, and their wavelengths of absorption maximum λmax were recorded. Also, the 234 λmax values of 1-substituted phenyl-2-arylethylene compounds (XAEY, where X is substituted phenyl) were collected. The excited-state substituent constants (Formula presented.) of three pyridyl groups and 23 substituted phenyl groups (total of 26) were obtained by means of curve-fitting method. Taking the λmax values of 358 samples of bi-arylethene derivatives as a data set and 126 samples of bi-aryl Schiff bases (including nine compounds synthesized by this work) as another data set, quantitative correlation analyses were performed by employing the obtained (Formula presented.) as a parameter, and good results were obtained for the two data sets. The reliability of the obtained (Formula presented.) values was verified. The results of this paper can provide excited-state substituent constants for the study and application of optical properties of conjugated organic compounds containing aryl groups.
- Cao, Chao-Tun,Yan, Lu,Cao, Chenzhong
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- Chromium-Salen Complex/Nitroxyl Radical Cooperative Catalysis: A Combination for Aerobic Intramolecular Dearomative Coupling of Phenols
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We describe an aerobic intramolecular dearomative coupling reaction of tethered phenols using a catalytic system consisting of a chromium-salen (Cr-salen) complex combined with a nitroxyl radical. This novel catalytic system enables formation of various spirocyclic dienone products including those unable to be accessed by previously reported methods efficiently under mild reaction conditions.
- Nagasawa, Shota,Fujiki, Shogo,Sasano, Yusuke,Iwabuchi, Yoshiharu
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p. 6952 - 6968
(2021/05/29)
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- Alcohol-based Michaelis-Arbuzov reaction: An efficient and environmentally-benign method for C-P(O) bond formation
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The famous Michaelis-Arbuzov reaction is extensively used both in the laboratory and industry to manufacture tons of widely-used organophosphoryl compounds every year. However, this method and the modified Michaelis-Arbuzov reactions developed recently still have some limitations. We now report a new alcohol-version of the Michaelis-Arbuzov reaction that can provide an efficient and environmentally-benign method to address the problems of the known Michaelis-Arbuzov reactions. That is, a wide range of alcohols can readily react with phosphites, phosphonites, and phosphinites to give all the three kinds of phosphoryl compounds (phosphonates, phosphinates, and phosphine oxides) using an n-Bu4NI-catalyzed efficient C-P(O) bond formation reaction. This general method can also be easily scaled up and used for further synthetic transformations in one pot.
- Ma, Xiantao,Xu, Qing,Li, Huan,Su, Chenliang,Yu, Lei,Zhang, Xu,Cao, Hongen,Han, Li-Biao
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supporting information
p. 3408 - 3413
(2018/08/06)
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- Activation of anti-oxidant Nrf2 signaling by substituted trans stilbenes
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Nrf2, which is a member of the cap'n’ collar family of transcription factors, is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. The importance of inflammation and oxidative stress in many chronic diseases supports the concept that activation of anti-oxidant Nrf2 signaling may have therapeutic potential. A number of Nrf2 activators have entered into clinical trials. Nrf2 exists in the cytosol in complex with its binding partner Keap1, which is a thiol-rich redox-sensing protein. In response to oxidative and electrophilic stress, select cysteine residues of Keap1 are modified, which locks Keap1 in the Nrf2-Keap1 complex and allows newly synthesized Nrf2 to enter the nucleus. Numerous Nrf2-activating chemicals, including a number of natural products, are electrophiles that modify Keap1, often by Michael addition, leading to activation of Nrf2. One concern with the design of Nrf2 activators that are electrophilic covalent modifiers of Keap1 is the issue of selectivity. In the present study, substituted trans stilbenes were identified as activators of Nrf2. These activators of Nrf2 are not highly electrophilic and therefore are unlikely to activate Nrf2 through covalent modification of Keap1. Dose-response studies demonstrated that a range of substituents on either ring of the trans stilbenes, especially fluorine and methoxy substituents, influenced not only the sensitivity to activation, reflected in EC50values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2. The stilbene backbone appears to be a privileged scaffold for development of a new class of Nrf2 activators.
- Deck, Lorraine M.,Whalen, Lisa J.,Hunsaker, Lucy A.,Royer, Robert E.,Vander Jagt, David L.
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p. 1423 - 1430
(2017/02/18)
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- Synthetic method for alkyl group phosphorous acid diester compounds or alkyl group phosphinic acid ester compounds
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The invention discloses a synthetic method for alkyl group phosphorous acid diester compounds or alkyl group phosphinic acid ester compounds. According to the synthetic method, alcohols which are cheap, easy to get, wide in source, stable and low in toxicity serve as alkylating reagents, iodine salt which is cheap and easy to get serves as catalysts, no solvent is needed, and the alkyl group phosphorous acid diester compounds can be selectively directly obtained after a reaction. The reaction method is simple, the condition is mild, no organic solvent is needed and operation is simple. According to the method, the requirements for reaction conditions are low, various types of alcohols such as a benzyl group type, an allyl type and a fat type can be utilized as the alkylate reagents to implement the synthesis of different types of substituted alkyl group phosphorous acid diester, and the method can be further expanded to the synthesis of the alkyl group phosphinic acid ester compounds through the reaction between the substituted phosphonous acid diester and the alcohols.
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Paragraph 0046; 0047; 0048; 0049
(2017/04/26)
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- Difluorocyclobutylacetylenes as positive allosteric modulators of mGluR5 with reduced bioactivation potential
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Schizophrenia is a serious illness that affects millions of patients and has been associated with N-methyl-D-aspartate receptor (NMDAR) hypofunction. It has been demonstrated that activation of metabotropic glutamate receptor 5 (mGluR5) enhances NMDA receptor function, suggesting the potential utility of mGluR5 positive allosteric modulators (PAMs) in the treatment of schizophrenia. Herein we describe the optimization of an mGluR5 PAM by replacement of a phenyl with aliphatic heterocycles and carbocycles as a strategy to reduce bioactivation in a biaryl acetylene chemotype. Replacement with a difluorocyclobutane followed by further optimization culminated in the identification of compound 32, a low fold shift PAM with reduced bioactivation potential. Compound 32 demonstrated favorable brain uptake and robust efficacy in mouse novel object recognition (NOR) at low doses.
- Degnan, Andrew P.,Maxwell, Darrell,Balakrishnan, Anand,Brown, Jeffrey M.,Easton, Amy,Gulianello, Michael,Hanumegowda, Umesh,Hill-Drzewi, Melissa,Miller, Regina,Santone, Kenneth S.,Senapati, Arun,Shields, Eric E.,Sivarao, Digavalli V.,Westphal, Ryan,Whiterock, Valerie J.,Zhuo, Xiaoliang,Bronson, Joanne J.,Macor, John E.
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supporting information
p. 5871 - 5876
(2016/12/06)
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- A 2 - [2 - (3-methoxy-phenyl)-ethyl]-phenol synthesis method
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The invention discloses a synthetic method for 2-[2-(3-methoxyphenyl)ethyl]phenol. The method comprises: firstly synthesizing diethyl 3-methoxybenzylphosphonate and 2,2-dimethoxybenzaldehyde, then successively synthesizing 1-(2,2-dimethoxyphenyl)-2-(3-methoxyphenyl)ethylene, 1-(2-phenoxy)-2-(3-methoxyphenyl)ethylene, 1-(2-acetoxphenyl)-2-(3-methoxyphenyl)ethylene and 1-(2-acetoxphenyl)-2-(3-methoxyphenyl)ethane, and finally synthesizing the product 2-[2-(3-methoxyphenyl)ethyl]phenol. The prepared 2-[2-(3-methoxyphenyl)ethyl]phenol product is good in quality and high in yield.
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Paragraph 0017-0018
(2017/01/12)
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- NITROGENOUS HETEROCYCLIC DERIVATIVES AND THEIR APPLICATION IN DRUGS
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The present invention relates to the field of medicine, provided herein are novel nitrogenous heterocyclic compounds, their preparation methods and their uses as drugs, especially for treatment and prevention of tissue fibrosis. Also provided herein are pharmaceutically acceptable compositions comprising the nitrogenous heterocyclic compounds and the uses of the compositions in the treatment of human or animal tissue fibrosis, especially for human or animal renal interstitial fibrosis, glomerular sclerosis, liver fibrosis, pulmonary fibrosis, IPF, peritoneal fibrosis, myocardial fibrosis, dermatofibrosis, postsurgical adhesion, benign prostatic hyperplasia, skeletal muscle fibrosis, scleroderma, multiple sclerosis, pancreatic fibrosis, cirrhosis, myosarcoma, neurofibroma, pulmonary interstitial fibrosis, diabetic nephropathy, alzheimer disease or vascular fibrosis.
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Paragraph 00246
(2015/07/07)
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- Combined coinage metal catalysis in natural product synthesis: Total synthesis of (+)-varitriol and seven analogs
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A modular total synthesis of the natural product (+)-varitriol (1) and seven analogs was achieved by using combined coinage metal catalysis. Starting from enynol 13, reagent-controlled introduction of stereogenic centers and efficient center-to-axis-to-ce
- Sun, Tao,Deutsch, Carl,Krause, Norbert
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supporting information; experimental part
p. 5965 - 5970
(2012/08/27)
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- Riccardin C derivatives as anti-MRSA agents: Structure-activity relationship of a series of hydroxylated bis(bibenzyl)s
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Members of a series of macrocyclic bis(bibenzyl) riccardin-class derivatives were found to exhibit antibacterial activity towards methicillin-resistant Staphylococcus aureus (anti-MRSA activity). Structure-activity relationship (SAR) studies were conducted, focusing on the number and position of the hydroxyl groups. The minimum essential structure for anti-MRSA activity was also investigated.
- Sawada, Hiromi,Okazaki, Miki,Morita, Daichi,Kuroda, Teruo,Matsuno, Kenji,Hashimoto, Yuichi,Miyachi, Hiroyuki
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p. 7444 - 7447
(2013/02/21)
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- Synthesis of 3,5-diaryl substituted indole derivatives and its selective iodide ion chemosensing
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In this contribution, we have synthesized series of 1-ethyl-3,5-bis[2- (aryl)ethenyl]-1H-indole based derivatives with different functional groups using Wadsworth-Emmons coupling. The sensing ability of the receptors has been studied for halides like tetrabutylammonium fluoride, chloride, bromide, iodide and bisulphate by UV-vis spectroscopy methods. In THF solution, compound A-E exhibits excellent selectivity with iodide ions over the other ions like tetrabutylammonium bromide (TBABr), tetrabutylammonium chloride (TBACl), tetrabutylammonium fluoride (TBAF) and tetrabutylammonium bisulphate (TBAHSO4). The indole cores were observed effectively and selectively recognized biologically important iodide was reported. Significant absorption change was observed only for tetrabutylammonium iodide and no change with other anions. The absorption spectra indicated the formation of complex between host and guest is in 1:1 stoichiometric ratio. The association constants of A-E for iodide ions were found to be 3.2 × 104 M-1, 3.9 × 104 M-1, 4.2 × 103 M -1, 2.9 × 103 M-1 and 2.14 × 103 M-1, respectively.
- Rathikrishnan, Krishnaswamy R.,Indirapriyadharshini, Vellore K.,Ramakrishna, Seeram,Murugan, Rajendiran
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scheme or table
p. 640 - 644
(2012/02/05)
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- A practical synthesis of sarpogrelate hydrochloride and in vitro platelet aggregation inhibitory activities of its analogues
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A convenient approach for the preparation of sarpogrelate hydrochloride was developed. Two series of sarpogrelate hydrochloride analogues were designed and synthesized in order to improve their platelet aggregation inhibitory activities, biological tests suggested that these compounds have platelet aggregation inhibitory activities to some extent.
- Chen, Guo Hua,Wang, Sheng,Wu, Fei Hua
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scheme or table
p. 287 - 289
(2010/12/20)
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- Synthesis and evaluation of stilbene derivatives as a potential imaging agent of amyloid plaques
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Fluorescence probes that can detect Aβ (β-amyloid peptide) plaque are important tools for diagnosis of Alzheimer's disease (AD), and 4-N-methylamino-4′-hydroxystilbene (SB-13) is one of the promising candidate molecules. We report here the synthesis of SB-13 derivatives that consist of various electron donating/withdrawing moieties and distinct size of N-substituents. The synthesized compounds were screened for detection of Aβ40 fibrils in vitro. Four compounds exhibited more than sixfold intensity increase, and they were further analyzed for detail bindings and Aβ plaque imaging. Among these molecules, compound 42 meets two critical requirements for imaging agent; high fluorescence responsiveness and strong binding affinity. This compound showed more than 25-fold increase with the dissociation constant of 1.13 ± 0.37 μM. In AD mouse brain tissue, 42 selectively stained Aβ plaque, more specifically peripheral regions of Aβ plaque. This finding demonstrated its potential use as brain-imaging agents for AD studies.
- Hong, Myeng Chan,Kim, Yun Kyung,Choi, Jae Yong,Yang, Si Qiang,Rhee, Hakjune,Ryu, Young Hoon,Choi, Tae Hyun,Cheon, Gi Jeong,An, Gwang Il,Kim, Hye Yun,Kim, Youngsoo,Kim, Dong Jin,Lee, Jun-Seok,Chang, Young-Tae,Lee, Kyo Chul
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experimental part
p. 7724 - 7730
(2011/01/13)
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- Antimicrobial lexitropsins containing amide, amidine, and alkene linking groups
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The synthesis and properties of 80 short minor groove binders related to distamycin and the thiazotropsins are described. The design of the compounds was principally predicated upon increased affinity arising from hydrophobic interactions between minor groove binders and DNA. The introduction of hydrophobic aromatic head groups, including quinolyl and benzoyl derivatives, and of alkenes as linkers led to several strongly active antibacterial compounds with MIC for Staphylococcus aureus, both methicillin-sensitive and -resistant strains, in the range of 0.1-5 μg mL-1, which is comparable to many established antibacterial agents. Antifungal activity was also found in the range of 20-50 μg mL-1 MIC against Aspergillus niger and Candida albicans, again comparable with established antifungal drugs. A quinoline derivative was found to protect mice against S. aureus infection for a period of up to six days after a single intraperitoneal dose of 40 mg kg-1.
- Anthony, Nahoum G.,Breen, David,Clarke, Joanna,Donoghue, Gavin,Drummond, Allan J.,Ellis, Elizabeth M.,Gemmell, Curtis G.,Helesbeux, Jean-Jacques,Hunter, Iain S.,Khalaf, Abedawn I.,Mackay, Simon P.,Parkinson, John A.,Suckling, Colin J.,Waigh, Roger D.
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p. 6116 - 6125
(2008/09/16)
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- Synthesis, antitumor evaluation, and apoptosis-inducing activity of hydroxylated (E)-stilbenes
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The parallel solution-phase synthesis of a series of 30 monohydroxylated (E)-stilbene analogues is described. In vitro screening revealed low micromolar activity (GI50) against the MDA MB 468 breast cancer cell line. Activity in MDA MB 468 cells correlated with the ability to induce apoptosis following drug treatment by the most potent agents in the series, e.g., 5dy and 5jy, an observation further reinforced by Annexin V-FITC analysis and fluorescence microscopy.
- Lion, Cedric J.,Matthews, Charles S.,Stevens, Malcolm F. G.,Westwell, Andrew D.
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p. 1292 - 1295
(2007/10/03)
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- Reaction of phosphorus-stabilized carbanions with cyclic enones. Aromatization of the substitution and addition products
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α-Lithiated alkylphosphonic esters react with substituted cyclohex-2-enones either at the carbonyl group (addition yielding 2-hydroxyalkylphosphonic products) or at the β-carbon (addition-elimination yielding δ-keto phosphonates). Both types of products undergo smooth aromatization when treated with I2 in MeOH or with pyridinium perbromide in AcOH leading to a variety of benzylphosphonic esters substituted in the aromatic ring with the methoxy or hydroxy groups. Mechanisms of the aromatization reactions are discussed.
- Mphahlele, Malose J.,Pienaar, Andre,Modro, Tomasz A.
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p. 1455 - 1460
(2007/10/03)
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- α-FUNCTIONAL CYCLOALKYLPHOSPHONATES. I. SYNTHESIS
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Cycloalkylphosphonates 2 of different sizes (from cyclopropyl to cycloheptyl) bearing various functional groups Z in α-position were synthesized by bis-alkylation of α-functional methylphosphonates 1 and ω-dibromoalkanes in presence of base.The choice of the basic system is determined by the nature of Z.With powerful electron-withdrawing groups, NaH-THF/DMSO (Method A, for Z = CN, SO2R) or liquid-solid phase transfer process proved to be the more suitable systems.For Z = aryl or SR, lithium diisopropylamide is required to achieve the deprotonation.A wide range of new phoshonates were obtained in high yields on preparative scale.
- Nasser, Jamal,About-Jaudet, Elie,Collignon, Noel
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p. 171 - 179
(2007/10/02)
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