6388-47-2Relevant academic research and scientific papers
POLY-ADP RIBOSE POLYMERASE (PARP) INHIBITORS
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Page/Page column 27, (2018/07/29)
The present invention is related to a pharmaceutical composition comprising a pharmaceutically acceptable carrier or diluent and a compound represented by the following structural formula: The present invention is also related a method of treating a subject with a disease which can be ameliorated by inhibition of poly(ADP-ribose)polymerase (PARP). The definitions of the variables are provided herein.
Aromatic Halogenation by Using Bifunctional Flavin Reductase–Halogenase Fusion Enzymes
Andorfer, Mary C.,Belsare, Ketaki D.,Girlich, Anna M.,Lewis, Jared C.
, p. 2099 - 2103 (2017/10/07)
The remarkable site selectivity and broad substrate scope of flavin-dependent halogenases (FDHs) has led to much interest in their potential as biocatalysts. Multiple engineering efforts have demonstrated that FDHs can be tuned for non-native substrate scope and site selectivity. FDHs have also proven useful as in vivo biocatalysts and have been successfully incorporated into biosynthetic pathways to build new chlorinated aromatic compounds in several heterologous organisms. In both cases, reduced flavin cofactor, usually supplied by a separate flavin reductase (FR), is required. Herein, we report functional synthetic, fused FDH-FR proteins containing various FDHs and FRs joined by different linkers. We show that FDH-FR fusion proteins can increase product titers compared to the individual components for in vivo biocatalysis in Escherichia coli.
Extending the biocatalytic scope of regiocomplementary flavin-dependent halogenase enzymes
Shepherd, Sarah A.,Karthikeyan, Chinnan,Latham, Jonathan,Struck, Anna-Winona,Thompson, Mark L.,Menon, Binuraj R. K.,Styles, Matthew Q.,Levy, Colin,Leys, David,Micklefield, Jason
, p. 3454 - 3460 (2015/05/27)
Flavin-dependent halogenases are potentially valuable biocatalysts for the regioselective halogenation of aromatic compounds. These enzymes, utilising benign inorganic halides, offer potential advantages over traditional non-enzymatic halogenation chemistry that often lacks regiocontrol and requires deleterious reagents. Here we extend the biocatalytic repertoire of the tryptophan halogenases, demonstrating how these enzymes can halogenate a range of alternative aryl substrates. Using structure guided mutagenesis we also show that it is possible to alter the regioselectivity as well as increase the activity of the halogenases with non-native substrates including anthranilic acid; an important intermediate in the synthesis and biosynthesis of pharmaceuticals and other valuable products. This journal is
A High-Throughput Assay for Arylamine Halogenation Based on a Peroxidase-Mediated Quinone-Amine Coupling with Applications in the Screening of Enzymatic Halogenations
Hosford, Joseph,Shepherd, Sarah A.,Micklefield, Jason,Wong, Lu Shin
supporting information, p. 16759 - 16763 (2016/02/12)
Arylhalides are important building blocks in many fine chemicals, pharmaceuticals and agrochemicals, and there has been increasing interest in the development of more "green" halogenation methods based on enzyme catalysis. However, the screening and development of new enzymes for biohalogenation has been hampered by a lack of high-throughput screening methods. Described herein is the development of a colorimetric assay for detecting both chemical and enzymatic arylamine halogenation reactions in an aqueous environment. The assay is based on the unique UV/Vis spectrum created by the formation of an ortho-benzoquinone-amine adduct, which is produced by the peroxidase-catalysed benzoquinone generation, followed by Michael addition of either a halogenated or non-halogenated arylamine. This assay is sensitive, rapid and amenable to high-throughput screening platforms. We have also shown this assay to be easily coupled to a flavin-dependent halogenase, which currently lacks any convenient colorimetric assay, in a "one-pot" workflow.
METHOD FOR PRODUCING NITROBENZENE COMPOUND
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Paragraph 0180, (2014/06/24)
A method for producing a nitrobenzene compound represented by general formula (2), wherein R1 and R5 are the same or different, and each is a halogen atom or another functional group, and R2, R3, and R4 are the same or different, and each is a hydrogen atom or another functional group, comprises oxidizing an aniline compound represented by general formula (1), wherein R1, R2, R3, R4, and R5 are the same as described above, with hydrogen peroxide in the presence of a tungsten compound under an acidic condition, followed by oxidation with hydrogen peroxide under a neutral to alkaline condition.
Synthesis of novel quinazolinone derivatives with methyl (E)-2-(3-methoxy)acrylate moiety
Dong, Kui-Kui,Zhou, Hua-Hong,Guo, A-Rong,Chen, Tian,Wang, Yu-Liang
, p. 1039 - 1042 (2013/05/08)
A new series of quinazolinone derivatives with methyl (E)-2-(3-methoxy) acrylate moiety have been designed and synthesized. All target compounds had been identified by 1H NMR spectrum, IR spectrum and HR-MS (high resolution mass spectrum). Three target compounds (10a, 10e, 10h) were chosen to preliminarily test the antibacterial activities, the results showed that all three target compounds exhibited antibacterial activities against three bacterial strains (Proteobacteria, Salmonella, Colibacillus).
Substituents effects on activity of kynureninase from Homo sapiens and Pseudomonas fluorescens
Maitrani, Chandan,Phillips, Robert S.
, p. 4670 - 4677 (2013/07/26)
A series of substituted kynurenines (3-bromo-dl, 3-chloro-dl, 3-fluoro-dl, 3-methyl-dl, 5-bromo-l, 5-chloro-l, 3,5-dibromo-l and 5-bromo-3-chloro-dl) have been synthesized and tested for their substrate activity with human and Pseudomonas fluorescens kynureninase. All of the substituted kynurenines examined have substrate activity with both human as well as P. fluorescens kynureninase. For the human enzyme, 3- and 5-substituted kynurenines have k cat and kcat/Km values higher than l-kynurenine, but less than that of the physiological substrate, 3-hydroxykynurenine. However, 3,5-dibromo- and 5-bromo-3-chlorokynurenine have kcat and kcat/Km values close to that of 3-hydroxykynurenine with human kynureninase. The effects of the 3-halo substituents on the reactivity with human kynureninase may be due to electronic effects and/or halogen bonding. In contrast, for the bacterial enzyme, 3-methyl, 3-halo and 3,5-dihalokynurenines are much poorer substrates, while 3-fluoro, 5-bromo, and 5-chlorokynurenine have kcat and kcat/K m values comparable to that of its physiological substrate, l-kynurenine. Thus, 5-bromo and 5-chloro-l-kynurenine are good substrates for both human as well as bacterial enzyme, indicating that both enzymes have space for substituents in the active site near C-5. The increased activity of the 5-halokynurenines may be due to van der Waals contacts or hydrophobic effects. These results may be useful in the design of potent and/or selective inhibitors of human and bacterial kynureninase.
COMPOUNDS FOR THE PREVENTION AND TREATMENT OF CARDIOVASCULAR DISEASE
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Page/Page column 71-73, (2010/08/04)
Disclosed are novel compounds that are useful for regulating the expression of apolipoprotein A-I (ApoA-l), and their use for the treatment and prevention of cardiovascular disease and related disease states, including cholesterol- or lipid-related disorders, such as, for example, atherosclerosis. Also disclosed are pharmaceutical compositions comprising the novel compounds.
FUSED-RING PYRIMIDIN-4(3H)-ONE DERIVATIVES, PROCESSES FOR THE PREPARATION AND USES THEREOF
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Page 292; 293, (2010/02/06)
AbstractNovel compounds of the following formula (I) and pharmacologically acceptable salt and esters thereof can modulate LXR function and as a result show excellent anti-arteriosclerotic and anti-inflammatory activity:wherein:A represents aryl or heteroaryl;R1, R2 and R3 are the same or different and each represents hydrogen, hydroxyl, nitro, cyano, amino, halogen, carboxy, carbamoyl, mercapto, alkyl, haloalkyl, alkylcarbonyloxy, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, dialkylamino, alkylcarbonylamino, N-(alkylcarbonyl)-N-(alkyl)amino, alkoxycarbonylamino, N-(alkoxycarbonyl)-N-(alkyl)amino, alkylsulfonylamino, N-(alkylsulfonyl)-N-(alkyl)amino, haloalkylsulfonylamino, N-(haloalkylsulfonyl)-N-(alkyl)amino, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl group, or R1 and R2 together are alkylenedioxy;R4 and R5 are the same or different and each represents hydrogen, hydroxyl, amino, halogen, mercapto, alkyl, haloalkyl, alkoxy, alkoxycarbonyl or alkylthio;X represents hydrogen, hydroxyl, halogen, alkoxy or haloalkoxy; andY represents an optionally substituted alkyl, cycloalkyl, heterocyclyl, aryl, cycloalkylalkyl, heterocyclylalkyl or aralkyl group.
QUINAZOLINE DERIVATIVES AS ACETYLCHOLINESTERASE INHIBITORS
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, (2008/06/13)
A method of treating cognitive deficiencies is described by administering a quinazoline derivative of the general formula wherein A represents in which n is 1-10, P is a bond or (CH2)m in which m is 0-10, and M is =0 , =S , =NR, =CRR, novel compounds of the above are also described as well as methods of manufacture and pharmaceutical compositions.
