- The influence of key residues in the tunnel entrance and the active site on activity and selectivity of toluene-4-monooxygenase
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Site-directed saturation mutagenesis is a convenient method to fine tune enzyme activity and selectivity at known "hot spots". The objective of this work was to investigate the influence of mutations in the tunnel entrance of toluene 4-monooxygenase (T4MO
- Brouk, Moran,Derry, Netta-Lee,Shainsky, Janna,Zelas, Zohar Ben-Barak,Boyko, Yulia,Dabush, Keren,Fishman, Ayelet
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- BIFUNCTIONAL COMPOUNDS
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The invention provides a bifunctional compound of formula (I), or a pharmaceutically acceptable salt thereof, wherein said Targeting Ligand, Linker and Degron are as described herein.
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Page/Page column 51; 85
(2021/05/07)
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- Synthesis of high added value compounds through catalytic oxidation of 2-phenylethanol: A Kinetic study
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An effective procedure was developed to produce high-value added phenolic compounds through the conversion of 2-phenylethanol (2-PhEt) by using acid-activated clays KSF for the hydrogen peroxide. Owing to KSF's ability to catalyze a variety of complex oxi
- Ben Hmida, Rania,Frikha, Nourzed,Bouguerra Neji, Soumaya,Kit, Geoffrey,Medina, Francisco,Bouaziz, Mohamed
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p. 124 - 133
(2019/12/03)
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- 1-(1-Arylethylpiperidin-4-yl)thymine analogs as antimycobacterial TMPK inhibitors
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A series of Mycobacterium tuberculosis TMPK (MtbTMPK) inhibitors based on a reported compound 3 were synthesized and evaluated for their capacity to inhibit MtbTMPK catalytic activity and the growth of a virulent M. tuberculosis strain (H37Rv). Modifications of the scaffold of 3 failed to afford substantial improvements in MtbTMPK inhibitory activity and antimycobacterial activity. Optimization of the substitution pattern of the D ring of 3 resulted in compound 21j with improved MtbTMPK inhibitory potency (three-fold) and H37Rv growth inhibitory activity (two-fold). Moving the 3-chloro substituent of 21j to the para-position afforded isomer 21h, which, despite a 10-fold increase in IC50-value, displayed promising whole cell activity (minimum inhibitory concentration (MIC) = 12.5 μM).
- Boshoff, Helena I. M.,Caljon, Guy,Forbes, He Eun,Hulpia, Fabian,Jian, Yanlin,Munier-Lehmann, Hélène,Risseeuw, Martijn D. P.,van Calenbergh, Serge
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- Improving process conditions of hydroxytyrosol synthesis by toluene-4-monooxygenase
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Toluene-4-monooxygenase from Pseudomonas mendocina KR1 was recently engineered for the synthesis of hydroxytyrosol, a potent antioxidant. Following a 190-fold improvement in the enzyme activity by protein engineering means, improving the process conditions of this biocatalytic route was under taken for developing a liter-scale bioprocess. The growth stage was improved by selection of a rich media and harvesting the cells at the end of the logarithmic stage. The biotransformation stage was optimized by evaluating substrate concentration, cell density, and different operational modes. It was found that although reusing the cells in successive batch modes is feasible, their activity is dramatically decreased after the first use. In comparison, the activity of the cells following subsequent substrate addition in a fed batch mode was only slightly decreased. Furthermore, a better yield was obtained by extending the duration of the biotransformation stage, rather than adding more substrate. An overall concentration of 133 mg/L HTyr, corresponding to a volumetric productivity of 54 mg/L/h and a yield of 48% was achieved by a batch mode using 2 mM substrate. This is an order of magnitude improvement compared with the enzyme productivity before the process optimization. The use of beads conjugated with phenylboronic acid residues for adsorbing the product from the biotransformation bulk was evaluated. Though the recovery yield and purity were shown to be oppositely dependent, an average recovery procedure led to 2-fold purification of HTyr resulting in 84% purity with 70% recovery yield.
- Brouk, Moran,Fishman, Ayelet
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p. 121 - 127
(2012/11/07)
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- 1,2,4-Triazine Derivatives, Preparation and Use Thereof in Human Therapy
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The invention concerns 3,5-dioxo-(2H,4H)-1,2,4-triazine derivatives of general formula (I), wherein: R1 and R2, identical or different, represent a branched or linear C1-C7 alkyl or alkenyl radical, a C1/s
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Page/Page column 15
(2008/12/06)
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- FURAN-2-CARBOXYLIC ACID DERIVATIVES AND PROCESS FOR THE PREPARATION THEREOF
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This invention relates to a furan-2-carboxylic acid derivative capable of activating AMP-activated protein kinase (AMPK), which is useful for the prevention and treatment of metabolic syndromes including diabete, obesity, hyperlipidemia, hypercholesterole
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Page/Page column 10
(2010/11/30)
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- Selective ortho-cleavage of methoxymethyl- and 4-methoxybenzyl ethers
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Iodine in methanol has been found to be an effective catalyst system for the cleavage of alkoxymethyl ethers. This catalyst system is particularly useful for the selective removal of ortho-methoxymethyl- and ortho-(4-methoxybenzyl) ethers in the presence
- Keith, John M.
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p. 2739 - 2742
(2007/10/03)
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- PYRROLE DERIVATIVE
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A novel pyrrole derivative represented by the following formula (1) and a salt thereof: wherein R1 means substituted alkenyl, etc.; R2 means substituted benzoyl, etc.; and R3 to R5 each means hydrogen, alkyl, halogeno, etc. The derivative and salt have antidiabetic activity.
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- One-pot synthesis of 6-hydroxyisochromans: The example of demethyl-oxa-coclaurine
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Using a modified oxa-Pictet Spengler reaction that we recently described, we synthesized 6-hydroxy-isochromans and their 7-hydroxy derivatives. The successful one step synthesis did not require protecting groups and provided high yields. The obtainment of 1-(4′ -hydroxybenzyl)-6,7-dihydroxyisochroman (1) indicates that this protocol can be used to synthesize oxygenated analogues of benzyl-tetrahydroisoquinoline alkaloids, such as demethyl-coclaurine (2). This methodology could provide a general procedure for the synthesis of hydroxyisochromans. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Guiso, Marcella,Bianco, Armandodoriano,Marra, Carolina,Cavarischia, Claudia
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p. 3407 - 3411
(2007/10/03)
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- Pulsed Ultraviolet Laser Photolysis of Substituted Phenyl Diazosulphonates at 248 nm
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The photochemical decomposition of aqueous phenyl diazosulphonate solutions by KrF excimer laser pulses at 248 nm is investigated.The present study complements earlier investigations (Franzke et al. 1991, 1992) of the photochemistry of this class of compounds induced by irradiation at 308 nm (XeCl excimer laser), and in the 370-390 nm wavelength range (dye laser pulses).From the comparison, conclusions with regard to the wavelength dependent photolysis pathway are drawn.Phenyl diazosulphonates carrying methoxy- or ester-type substituents at the aromatic ring are observed to decompose in a two-step-reaction in aqueous solution: Photolysis proceeds via the phenyl diazonium ion as an intermediate, to yield the corresponding phenol as product.In contrast, the photolysis of 3-vinyl-phenyl diazosulphonate in aqueous solution at 248 nm results in a complex reaction involving via more than one intermediate.UV spectra recorded during photolysis show that products characterized by an absorption maximum at 272 nm are formed; these spectra are identical with those of final products from 308 nm photolysis, which are identified as 3-hydroxyethyl-phenols. - The photolysis pathway of 4-hydroxy-phenyl-diazosulphonate is found to proceed via the diazoquinone, instead of a diazonium ion.As a consequence of the high energy of 248 nm photons, the mentioned substituted phenols are not the final products of the photochemical reaction.These molecules are further decomposed by absorbing 248 nm photons; the quantum efficiency of these secondary photochemical reactions is lower by one to two orders of magnitude, as compared to the primary photolysis of the parent compounds. - Keywords: Light, Absorption / Materials Properties, Diazo Sulphonates / Photochemistry / Radicals / Spectroscopy, Ultraviolet
- Nomayo, M.,Wokaun, A.
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p. 1495 - 1503
(2007/10/02)
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- Nonprostanoid prostacyclin mimetics. 3. Structural variations of the diphenyl heterocycle moiety
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4,5-Diphenyl-2-oxazolenonanoic acid (2) and 2-[3-[2-(4,5-diphenyl-2- oxazolyl)ethyl]phenoxy]acetic acid (3) were previously identified as nonprostanoid prostacyclin (PGI2) mimetics that inhibit ADP-induced aggregation of human platelets in vitro. The effects on biological activity of substitution and structural modification of the 4- and 5-phenyl rings of 3 was examined. Potency showed a marked sensitivity to the introduction of substituents to these aromatic rings and only the bis-4-methyl derivative 9j, IC50 = 0.34 μM, demonstrated enhanced potency compared to the parent structure 3, IC50 = 1.2 μM. Substitution at the ortho or meta positions of the phenyl rings, replacement by thiopheneyl or cyclohexyl moieties, or constraining in a planar phenanthrene system resulted in compounds that were less effective inhibitors of ADP-induced platelet aggregation. In contrast, variation of the heterocycle moiety revealed a much less stringent SAR and many 5- and 6-membered heterocycles were found to effectively substitute for the oxazole ring of 2 and 3. The diphenylmethyl moiety functioned as an effective isostere for 4,5-diphenylated heterocycles since 13aad showed similar platelet inhibitory activity to 3. With the exception of the 3,4,5- triphenylpyrazole derivative 13g, compounds presenting the (m- ethylphenoxy)acetic acid side chain discovered with 3 demonstrated enhanced potency compared to the analogously substituted alkanoic acid derivative. The structure-activity findings led to a refinement of a model of the nonprostanoid PGI2 mimetic pharmacophore.
- Meanwell,Rosenfeld,Trehan,Romine,Wright,Brassard,Buchanan,Federici,Fleming,Gamberdella,Zavoico,Seiler
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p. 3498 - 3512
(2007/10/02)
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