- Aryl phenol compound as well as synthesis method and application thereof
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The invention discloses a synthesis method of an aryl phenol compound shown as a formula (3). All systems are carried out in an air or nitrogen atmosphere, and visible light is utilized to excite a photosensitizer for catalyzation. In a reaction solvent, ArNR1R2 as shown in a formula (1) and water as shown in a formula (2) are used as reaction raw materials and react under the auxiliary action of acid to obtain the aryl phenol compound as shown in a formula (3). The ArNR1R2 in the formula (1) can be primary amine and tertiary amine, can also be steroid and amino acid derivatives, and can also be drugs or derivatives of propofol, paracetamol, ibuprofen, oxaprozin, indomethacin and the like. The synthesis method has the advantages of cheap and easily available raw materials, simple reaction operation, mild reaction conditions, high reaction yield and good compatibility of substrate functional groups. The fluid reaction not only can realize amplification of basic chemicals, but also can realize amplification of fine chemicals, such as synthesis of drugs propofol and paracetamol. The invention has wide application prospect and use value.
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Paragraph 0133-0136
(2021/05/12)
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- DDX3X inhibitors, an effective way to overcome HIV-1 resistance targeting host proteins
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The huge resources that had gone into Human Immunodeficiency virus (HIV) research led to the development of potent antivirals able to suppress viral load in the majority of treated patients, thus dramatically increasing the life expectancy of people living with HIV. However, life-long treatments could result in the emergence of drug-resistant viruses that can progressively reduce the number of therapeutic options, facilitating the progression of the disease. In this scenario, we previously demonstrated that inhibitors of the human DDX3X helicase can represent an innovative approach for the simultaneous treatment of HIV and other viral infections such as Hepatitis c virus (HCV). We reported herein 6b, a novel DDX3X inhibitor that thanks to its distinct target of action is effective against HIV-1 strains resistant to currently approved drugs. Its improved in vitro ADME properties allowed us to perform preliminary in vivo studies in mice, which highlighted optimal biocompatibility and an improved bioavailability. These results represent a significant advancement in the development of DDX3X inhibitors as a novel class of broad spectrum and safe anti-HIV-1 drugs.
- Boccuto, Adele,Botta, Maurizio,Brai, Annalaura,Bugli, Francesca,Dreassi, Elena,Garbelli, Anna,Giannini, Alessia,Maga, Giovanni,Martini, Maurizio,Pennisi, Carla,Riva, Valentina,Saladini, Francesco,Sanguinetti, Maurizio,Trivisani, Claudia Immacolata,Zamperini, Claudio,Zazzi, Maurizio
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supporting information
(2020/05/22)
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- The highly efficient air oxidation of aryl and alkyl boronic acids by a microwave-assisted protocol under transition metal-free conditions
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Molecular oxygen is the most important green-oxidant due to its excellent properties. However, the effective utilization of molecular oxygen remains a major challenge in modern chemistry. Herein, we report the development a rapid, green and efficient microwave-assisted protocol for the air oxidation of boronic acids to phenols and alcohols under transition metal-free conditions. In the presence of KOH and DMSO, high yields of the expected phenols and alcohol were obtained with microwave-assistance, and a variety of functional groups were tolerated in this procedure. Notably, this transition metal-free method represents a breakthrough in both organic synthesis and green chemistry for the oxidative hydroxylation of boronic acids to phenols and alcohols.
- Yin, Weiyan,Pan, Xizhi,Leng, Wenxi,Chen, Jian,He, Haifeng
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supporting information
p. 4614 - 4618
(2019/09/09)
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- Cell-Based Optimization of Covalent Reversible Ketoamide Inhibitors Bridging the Unprimed to the Primed Site of the Proteasome β5 Subunit
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The ubiquitin-proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly-reversibly binding boronates, optimization of novel covalent-reversibly binding warheads remains largely unattended. We previously reported α-ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy-substituted α-ketoamides combining the structure-activity relationships from the primed and the non-primed site of the proteasome β5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1′ by a 3-phenoxy group to increase β5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time-dependent inhibition of cellular substrate conversion. Furthermore, the α-ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity.
- Stubba, Daniel,Bensinger, Dennis,Steinbacher, Janika,Proskurjakov, Lilia,Salcedo Gómez, álvaro,Schmidt, Uwe,Roth, Stefan,Schmitz, Katja,Schmidt, Boris
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supporting information
p. 2005 - 2022
(2019/11/22)
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- USE OF DDX3 INHIBITORS AS ANTIPROLIFERATIVE AGENTS
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The present invention refers to compounds of formula I or II endowed with DDX3 inhibitory activity, relative pharmaceutical compositions and their use as antihyperproliferative agents. (I) or (II)
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Page/Page column 85
(2017/10/30)
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- Tertiary Butyl Nitrite Triggered Nitration of Phenols: Solvent- and Structure-Dependent Kinetic Study
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Nitration of phenols with tertiary butyl nitrite (TBN) obeyed second-order kinetics with a first-order dependence on [TBN] and [phenol] under acid-free conditions. Reaction rates were significantly altered by a change in the dielectric constant and other physical properties of solvent. The rate of nitration increased with an increase in temperature (303-323 K) in different solvent media (acetonitrile, dichloroethane, CCl4, dimethyl formamide (DMF), and toluene). The rates of nitration (log k) could not fit into either Amis or Kirkwood plots [log k' vs. (1/D) or [(D - 1)/(2D + 1)], but the trends were better explained by the basic form of multivariate linear solvent energy relationships (MLSER) suggested by the Koppel and Palm approach on the one hand and the Kamlet and Taft approach on the other hand. These observations probably substantiate that cumulative contributions of basic solvent parameters (equilibrium as well as frictional solvent effects) and solvent-solute interactions for solvation of transition state during nitration of phenols. Reaction rates accelerated with the introduction of electron-donating groups and retarded with electron-withdrawing groups. Accordingly, the reactivity of structurally different phenols was found to follow the following sequence: p-OH > p-MeO > p-Me > H > m-Me > p-Cl > p-Br > m-Cl > p-NO2 > m-OH. The results are interpreted by Hammett's theory of linear free energy relationship. The reaction constant (Hammett's ρ) is a measure of the sensitivity of the reaction toward the electronic effects of the substituent. The rho (ρ) values obtained from the present experiments are fairly large negative values (ρ CH3) versus σ? or, Es or combined Taft's relationship. However, Charton's MLRA of the log k with polar, resonance, steric, hydrophobicity, and molar refractivity showing a very good linear relationship was obtained. It is of interest to note that when log kexp values are correlated with log kcal a perfect linearity is obtained with a correlation coefficient of unity, indicating the consonance between experimental and calculated rate constants in the present work.
- Kumar, M. Satish,Rajanna,Venkateswarlu,Rao, K. Lakshman
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supporting information
p. 171 - 196
(2016/04/09)
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- HUMAN HELICASE DDX3 INHIBITORS AS THERAPEUTIC AGENTS
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The present invention refers to compounds endowed with RNA helicase DDX3 inhibitory activity of formula I and II and their therapeutic use, in particular for the treatment of viral diseases.
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Page/Page column 92; 93
(2016/09/22)
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- Ultrasonic and microwave-assisted synthesis of β-nitro styrenes and nitro phenols with tertiary butyl nitrite under acid-free conditions
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Tertiary butyl nitrite (TBN) is an acid-free and safe nitrating agent that provides preferentially β-nitrostyrenes with cinnamic acids and corresponding nitro derivatives with phenols in good yields under classical conditions. However, ultrasonic and microwave-assisted reactions reduced the reaction times substantially and enhanced the yields from good to excellent. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications to view the free supplemental file.
- Kumar, M. Satish,Rajanna,Reddy, K. Rajendar,Venkateswarlu,Venkanna
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supporting information
p. 2672 - 2677
(2013/07/26)
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- Fast and efficient nitration of salicylic acid and some other aromatic compounds over H3PO4/TiO2-ZrO2 using nitric acid
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TiO2-ZrO2 (1/1)-surf with Ti and Zr molar ratio of 1/1 was prepared with surfactant through a sol-gel method. The optimum experimental condition was investigated for nitration of salicylic acid. Then, a number of nitration reactions were carried out with a variety of aromatic compounds in the optimum condition. The 25 wt% H3PO4/TiO2-ZrO2 (1/1)-surf catalyst showed good selectivity and yield in a short time for the nitration of salicylic acid and some other aromatic compounds.
- Kalbasi, Roozbeh Javad,Massah, Ahmad Reza,Zamani, Farzad,Hamid, Javaherian Naghash
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experimental part
p. 397 - 403
(2010/10/20)
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- Catalytic asymmetric intramolecular hydroarylations of ω-aryloxy- and arylamino-tethered α,β-unsaturated aldehydes
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The first enantioselective organocatalytic intramolecular hydroarylations of phenol and aniline-derived enals were investigated. The proposed method provided an atom economic and straightforward approach to optically active chromans and tetrahydroquinolines in high enantioselectivities and in good yields. The study demonstrated the efficiency of organocatalysis to achieve the first asymmetric intramolecular arylation of ω aryloxy- arylamino-tethered α, and β-unsaturated aldehydes using a chiral secondary amine catalyst. Proposed transformation method resulted in the production of functionalized chromans and tetrahydroquinoline in high enantiopurity. The study also examined the scope of substrates in this organocatalytic reaction using a catalyst 4/p-TsOH.H2O in diethyl ether. The catalyst screening observed a higher yield up to 83% and comparable enantiometric excess up to 88% that can be obtained in a chiral secondary amine employed as the reaction catalyst.
- Lu, Hai-Hua,Liu, Hui,Wu, Wei,Wang, Xu-Fan,Lu, Liang-Qiu,Xiao, Wen-Jing
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supporting information; scheme or table
p. 2742 - 2746
(2009/12/03)
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- Zeolite H-Y-supported copper(II) nitrate: A simple and effective solid-supported reagent for nitration of phenols and their derivatives
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Highly regiospecific mononitration of phenols and substituted phenols is accomplished by employing copper(II) nitrate supported on a catalytic amount of zeolite H-Y in a solid state. Copyright Taylor & Francis Group, LLC.
- Lalitha,Sivakumar
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p. 1745 - 1752
(2008/09/20)
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- Regioselectivity of the nitration of phenol by acetyl nitrate adsorbed on silica gel
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The reaction of phenol with acetyl nitrate in chloroform gives nitrophenol with an ortho/para ratio of 1.8. This ratio increase to 13.3 when the reaction was carried out with acetyl nitrate pre-adsorbed on dry silica gel. Silica may be acting as a template to bring phenol close to acetyl nitrate by hydrogen bonds forming a ternary complex, which undergoes a six- center rearrangement to o-nitrophenol. The formation of this ternary complex is evaluated by ab initio molecular orbital calculation.
- Augusto,Rodrigues,De Oliveira Filho, Antonio Pedro,Moran, Paulo J. S.,Custodio, Rogerio
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p. 6733 - 6738
(2007/10/03)
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- Synthesis of camalexin and related phytoalexins
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A number of 3-(2′-thiazoyl)indoles, including two recently reported phytoalexins, have been prepared from the Grignard reaction of the corresponding substituted indole and 2-bromothiazole. The antifungal activity of these 3-(2′-thiazoyl)indoles and 3-(2′-oxazolyl)indole have been examined.
- Ayer, William A.,Craw, Peter A.,Ma, Yu-Ting,Miao, Shichang
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p. 2919 - 2924
(2007/10/02)
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- Convenient Synthesis of 6-Methoxyindole and 6-Methoxytryptophyl Bromide
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A preparatively convenient synthesis of 6-methoxyindole (7) and 6-methoxytryptophylbromide (11) is presented starting with p-cresol (1).Regioselective nitration of p-cresol carbonate (2) followed by hydrolysis of the carbonate and methylation gives 4-methoxy-2-nitrotoluene (5) which is converted to 7 by esterification, reduction and bromination yields 6-methoxytryptophyl bromide (11).The overall yield of 7 and 11 from p-cresol is 43percent and 25percent respectively.
- Feldman, Paul L.,Rapoport, Henry
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p. 735 - 737
(2007/10/02)
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- SELECTIVE NITRATION OF PHENOLS CATALYZED BY LANTHANUM (III) NITRATE
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Phenols are easily mononitrated at room temperature by NaNO3 in a two-phase system (water - ether) in presence of HCl and a catalytic amount of La(NO3)3.The experimental conditions leave completely unaltered many other aromatic systems.
- Ouertani, M.,Girard, P.,Kagan, H.B.
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p. 4315 - 4318
(2007/10/02)
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- (3-Nitro-4-methyl)-phenyl chloroformate and its preparation
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The novel compound (3-nitro-4-methyl)-phenyl chloroformate is prepared by reacting (4-methyl)-phenyl chloroformate with nitric acid in the presence of sulfuric acid. The novel compound (3-nitro-4-methyl)-phenyl chloroformate is a valuable starting material for the preparation of dyes and crop protection agents and in particular is an intermediate for the preparation of 3-nitro-4-methylphenol, which is reduced to 3-amino-4-methylphenol.
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- 2-Amino-4-hydroxy-5-chloro toluene and the hydrochloride thereof
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2-Amino-4-hydroxy-5-chloro toluene and the hydrochloride thereof are couplers usefully employed in the production of a hair dye by reaction with an aromatic paradiamine.
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