28286-79-5Relevant academic research and scientific papers
Investigation of the requirements for efficient and selective cytochrome P450 monooxygenase catalysis across different reactions
Podgorski, Matthew N.,Coleman, Tom,Chao, Rebecca R.,De Voss, James J.,Bruning, John B.,Bell, Stephen G.
, (2019/11/22)
The cytochrome P450 metalloenzyme (CYP) CYP199A4 from Rhodopseudomonas palustris HaA2 catalyzes the highly efficient oxidation of para-substituted benzoic acids. Here we determined crystal structures of CYP199A4, and the binding and turnover parameters, with different meta-substituted benzoic acids in order to establish which criteria are important for efficient catalysis. When compared to the para isomers, the meta-substituted benzoic acids were less efficiently oxidized. For example, 3-formylbenzoic acid was oxidized with lower activity than the equivalent para isomer and 3-methoxybenzoic acid did not undergo O-demethylation by CYP199A4. The structural data highlighted that the meta-substituted benzoic acids bound in the enzyme active site in a modified position with incomplete loss of the distal water ligand of the heme moiety. However, for both sets of isomers the meta- or para-substituent pointed towards, and was in close proximity, to the heme iron. The absence of oxidation activity with 3-methoxybenzoic acid was assigned to the observation that the C[sbnd]H bonds of this molecule point away from the heme iron. In contrast, in the para isomer they are in an ideal location for abstraction. These findings were confirmed by using the bulkier 3-ethoxybenzoic acid as a substrate which removed the water ligand and reoriented the meta-substituent so that the methylene hydrogens pointed towards the heme, enabling more efficient oxidation. Overall we show relatively small changes in substrate structure and position in the active site can have a dramatic effect on the activity.
Diphenyl urea anti-tumor micromolecule inhibitor and preparation method thereof (by machine translation)
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Paragraph 0108-0111, (2019/10/01)
The invention discloses a diphenyl urea anti-tumor small molecule inhibitor. The small molecule inhibitor may be represented formula I, Formula II, or Formula III. The small-molecule inhibitor specifically targets UBABA3, has good anti-tumor activity, and can be used as a good anti-tumor treatment small molecule inhibitor in the half inhibition concentration (IC50 5 μm) of various human non-small cell lung cancer cells. The small molecule inhibitor effect target is clear, and is different from MLNNNNN4924, and NAE enzyme activity inhibition mechanisms, respectively, are inhibited. Neddddylation modification cullin in the framework structure of the ubiquitin-modified key enzyme CRL ligase can be effectively inhibited, so that activation, CRL ligase activation is inhibited, and tumor growth inhibition effect is achieved. (by machine translation)
Polypyridyl iridium(III) based catalysts for highly chemoselective hydrogenation of aldehydes
Pandrala, Mallesh,Resendez, Angel,Malhotra, Sanjay V.
, p. 283 - 288 (2019/09/30)
Iridium-catalyzed transfer hydrogenation (TH) of carbonyl compounds using HCOOR (R = H, Na, NH4) as a hydrogen source is a pivotal process as it provides the clean process and is easy to execute. However, the existing highly efficient iridium catalysts work at a narrow pH; thus, does not apply to a wide variety of substrates. Therefore, the development of a new catalyst which works at a broad pH range is essential as it can gain a broader scope of utilization. Here we report highly efficient polypyridyl iridium(III) catalysts, [Ir(tpy)(L)Cl](PF6)2 {where tpy = 2,2′:6′,2′'-Terpyridine, L = phen (1,10-Phenanthroline), Me2phen (4,7-Dimethyl-1,10-phenanthroline), Me4phen (3,4,7,8-Tetramethyl-1,10-phenanthroline), Me2bpy (4,4′-Dimethyl-2–2′-dipyridyl)} for the chemoselective reduction of aldehydes to alcohols in aqueous ethanol and sodium formate as the hydride source. The reaction can be carried out efficiently in broad pH ranges, from pH 6 to 11. These catalysts are air stable, easy to prepare using commercially available starting materials, and are highly applicable for a wide range of substrates, such as electron-rich or deficient (hetero)arenes, halogens, phenols, alkoxy, ketones, esters, carboxylic acids, cyano, and nitro groups. Particularly, acid and hydroxy groups containing aldehydes were reduced successfully in basic and acidic reaction conditions, demonstrating the efficiency of the catalyst in a broad pH range with high conversion rates under microwave irradiation.
Iridium-catalyzed highly efficient chemoselective reduction of aldehydes in water using formic acid as the hydrogen source
Yang, Zhanhui,Zhu, Zhongpeng,Luo, Renshi,Qiu, Xiang,Liu, Ji-Tian,Yang, Jing-Kui,Tang, Weiping
supporting information, p. 3296 - 3301 (2017/07/28)
A water-soluble highly efficient iridium catalyst is developed for the chemoselective reduction of aldehydes to alcohols in water. The reduction uses formic acid as the traceless reducing agent and water as a solvent. It can be carried out in air without the need for inert atmosphere protection. The products can be purified by simple extraction without any column chromatography. The catalyst loading can be as low as 0.005 mol% and the turn-over frequency (TOF) is as high as 73 800 mol mol-1 h-1. A wide variety of functional groups, such as electron-rich or deficient (hetero)arenes and alkenes, alkyloxy groups, halogens, phenols, ketones, esters, carboxylic acids, cyano, and nitro groups, are all well tolerated, indicating excellent chemoselectivity.
Ru(II) complexes bearing 2,6-bis(benzimidazole-2-yl)pyridine ligands: A new class of catalysts for efficient dehydrogenation of primary alcohols to carboxylic acids and H2in the alcohol/CsOH system
Dai, Zengjin,Luo, Qi,Meng, Xianggao,Li, Renjie,Zhang, Jing,Peng, Tianyou
, p. 11 - 18 (2016/12/16)
Mono-cationic Ru(II)-complexes [Ru(L)X(CH3CN)2]?X 1～4 (1, L = 2,6-bis(benzimidazol-2-yl) pyridine (L1), X = Cl; 2, L = L1, X = OTf; 3, L = 2-(N-benzyl-benzimidazole-2-yl)-6-(benzimidazole-2-yl)pyridine (L2), X = Cl; 4, L = 2,6-bis(N-benzyl-benzimidazole-2-yl)pyridine (L3), X = Cl) were prepared and fully characterized. The two acetonitrile ligands of each complex are coordinated to the metal center cis to each other. Complex 2 was also structurally characterized by X-ray crystallography. It was found that complexes 1～4 can catalyze the acceptorless dehydrogenation of primary alcohols to corresponding carboxylic acids and H2in the basic aqueous solution, and the reactivity follows the order 1 = 2 > 4 > 3. Furthermore, complexes 1 or 2 can efficiently catalyze the conversion of various primary alcohols to carboxylic acid in good yields (72%–98%) and high selectivity in an alcohol/CsOH system (1/1, mol/mol). Using an excess amount of alcohol to CsOH results in the formation of the carboxylic acid in higher yield (up to 100%, based on CsOH) and higher turnover numbers (TON ～ 10000) accompanied by the H2evolution. Complexes 1 and 2 can act as a new class of phosphine- and N-heterocycle carbene free Ru(II) complexes for efficient conversion of primary alcohols to carboxylic acids and H2in a homogeneous system.
Electrophilicity and nucleophilicity of commonly used aldehydes
Pratihar, Sanjay
, p. 5781 - 5788 (2014/07/22)
The present approach for determining the electrophilicity (E) and nucleophilicity (N) of aldehydes includes a kinetic study of KMNO4 oxidation and NaBH4 reduction of aldehydes. A transition state analysis of the KMNO4 promoted aldehyde oxidation reaction has been performed, which shows a very good correlation with experimental results. The validity of the experimental method has been tested using the experimental activation parameters of the two reactions. The utility of the present approach is further demonstrated by the theoretical versus experimental relationship, which provides easy access to E and N values for various aldehydes and offers an at-a-glance assessment of the chemical reactivity of aldehydes in various reactions. the Partner Organisations 2014.
NHC-catalysed highly selective aerobic oxidation of nonactivated aldehydes
Moehlmann, Lennart,Ludwig, Stefan,Blechert, Siegfried
, p. 602 - 607 (2013/04/24)
This publication describes a highly selective oxidation of aldehydes to the corresponding acids or esters. The reaction proceeds under metal-free conditions by using N-heterocyclic carbenes as organocatalysts in combination with environmentally friendly oxygen as the terminal oxidation agent.
Application of complementary mass spectrometric techniques to the identification of ketoprofen phototransformation products
Kosjek, Tina,Perko, Silva,Heath, Ester,Kralj, Bogdan,Zigon, Dusan
experimental part, p. 391 - 401 (2011/11/12)
Ketoprofen (KP) is a nonsteroidal anti-inflammatory drug, which during UV irradiation rapidly transforms into benzophenone derivatives. Such transformation products may occur after topical application of KP, which is then exposed to sunlight resulting in a photo-allergic reaction. These reactions are mediated by the benzophenone moiety independently of the amount of allergen. The same reactions will also occur during wastewater or drinking water treatment albeit their effect in the aqueous environment is yet to be ascertained. In addition, only a few such transformation products have been recognised. To enable the detection and structural elucidation of the widest range of KP transformation products, this study applies complementary chromatographic and mass spectrometric techniques including gas chromatography coupled to single quadrupole or ion trap mass spectrometry and liquid chromatography hyphenated with quadrupole-time-of-flight mass spectrometry. Based on structural information gained in tandem and multiple MS experiments, and on highly accurate molecular mass measurements, chemical structures of 22 transformation products are proposed and used to construct an overall breakdown pathway. Among the identified transformation products all but two compounds retained the benzophenone moietya€"a result, which raises important issues concerning the possible toxic synergistic effects of KP and its transformation products. These findings trigger further research into water treatment technologies that would limit their entrance into environmental or drinking waters. Copyright
PIPERIDINE DERIVATIVES AS MODULATORS OF CHEMOKINE RECEPTOR ACTIVITY
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Page/Page column 103, (2009/03/07)
The present application describes modulators of MIP-1 of formula (I) : or stereoisomers or pharmaceutically acceptable salts thereof, wherein m, Q, T, W, Z, R1, R3, R4, R5, R5a and R5b, are as set forth above. In addition, methods of treating and preventing inflammatory diseases such as asthma and allergic diseases, as well as autoimmune pathologies such as rheumatoid arthritis and atherosclerosis using the modulators are disclosed.
Dual Pharmacophores - PDE4-Muscarinic Antagonistics
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Page/Page column 84, (2009/08/16)
The present invention is directed to novel compounds of Formula (I), pharmaceutical compositions and their use in therapy, for example as inhibitors of phosphodiesterase type IV (PDE4) and as antagonists of muscarinic acetylcholine receptors (mAChRs), in the treatment of/and or prophylaxis of respiratory diseases, including antiinflammatory and/or allergic diseases such as chronic obstructive pulmonary disease (COPD), asthma, rhinitis (e.g. allergic rhinitis), atopic dermatitis or psoriasis.
