- DRUGS AND COMPOSITIONS FOR OCULAR DELIVERY
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New prodrugs of therapeutically active compounds, including oligomeric prodrugs of ethacrynic acid, and compositions to treat medical disorders, for example glaucoma, a disorder or abnormality related to an increase in intraocular pressure (IOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy. Also a method for the controlled administration of timolol to a patient in need thereof, such as a human, comprising administering a prodrug of timolol in a microparticle in vivo, wherein the timolol prodrug containing microparticle exhibits in vitro drug release kinetics in an aqueous solution at a pH between 6-8 at body temperature of a substantially consistent release of at least 60% timolol itself by molar ratio to the prodrug of timolol or an intermediate metabolite thereof over at least 100 days.
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Page/Page column 160; 161
(2019/07/19)
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- Synthesis of α,β-unsaturated esters of perfluoropolyalkylethers (PFPAEs) based on hexafluoropropylene oxide units for photopolymerization
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α,β-unsaturated esters are usually synthesized for polymer applications. However, the addition of maleate (cis-configuration) to a fluorinated moiety is challenging due to its potential isomerization during esterification. Various synthetic routes were attempted and led to very low conversion or side-products. The immiscibility of both reagents combined with an easy isomerization or attack on the double bond were potential explanations. In this paper, the synthesis of maleates oligo(hexafluoropropylene oxide) is reported by Steglich esterification and the reaction conditions are discussed depending on the molecular weight of the fluorinated moieties. After UV-curing, hydrophobic polymers were obtained by copolymerization with vinyl ethers by electron acceptor-donor systems.
- Bonneaud, Céline,Decostanzi, Mélanie,Burgess, Julia,Trusiano, Giuseppe,Burgess, Trevor,Bongiovanni, Roberta,Joly-Duhamel, Christine,Friesen, Chadron M.
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p. 32664 - 32671
(2018/10/15)
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- DRUGS AND COMPOSITIONS FOR THE TREATMENT OF OCULAR DISORDERS
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The present invention provides new prodrugs of therapeutically active compounds, including oligomeric prodrugs, and compositions to treat medical disorders, for example glaucoma, a disorder or abnormality related to an increase in intraocular pressure (IOP), a disorder requiring neuroprotection, age-related macular degeneration, or diabetic retinopathy.
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Page/Page column 245; 383
(2018/10/19)
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- Preparation method of ethyl 4-(3,4-dimethoxyphenyl)-4-oxo-2-butenoate
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The invention relates to a preparation method of ethyl 4-(3,4-dimethoxyphenyl)-4-oxo-2-butenoate, and belongs to the technical field of chemical reagent synthesis. The preparation method comprises thefollowing steps: firstly performing an esterification reaction on maleic anhydride and ethanol, then performing a transposition reaction to obtain monoethyl fumarate, then performing a reaction on the monoethyl fumarate and sulfoxide chloride to obtain monoethyl monoacyl chloride fumarate, finally performing a reaction on the monoethyl monoacyl chloride fumarate and 1,2-dimethoxybenzene to obtaina target product ethyl 4-(3,4-dimethoxyphenyl)-4-oxo-2-butenoate, and refining to obtain a refined product. By the preparation method, a reaction product in each step is relatively high in yield andpurity, the finally prepared refined product is also high in yield and purity, and raw materials are simple, easy to obtain and low in cost; in addition, the preparation method is easy to operate, impurities in the product are easily separated and removed, and the refined product has the purity of 99% or above and fully meets requirements of customers for a medical purpose.
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Paragraph 0027; 0029; 0038; 0041; 0042; 0043
(2018/11/03)
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- Synthesis, DFT and antimicrobial activity assays in vitro for novel cis/trans-but-2-enedioic acid esters
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Six novel cis/trans-but-2-enedioic acid esters had been synthesized to discover the new bioactive molecules that could kill food-related bacteria and fungi. Their structures were analyzed by melting point, LC-MS, 1H NMR and 13C NMR. 4-(Methoxycarbonyl) phenyl ethyl fumarate (6b) was also characterized by single-crystal X-ray diffraction. Their antimicrobial activities were evaluated in vitro by measuring the minimal inhibitory concentration (MIC). Compared with the single monomethyl fumarate and methyl 4-hydroxybenzoate, these compounds had stronger antimicrobial activity against all the eight microorganisms. Among the antibacterial and antifungal compounds, 4-(methoxycarbonyl) phenyl methyl fumarate (6a) showed the best antimicrobial activity. The electronic properties of these compounds were calculated by the density functional theory (DFT) method with 6-31G (d, p) basis set. DFT studies indicated that molecular electrostatic potential (MEP) map, ELUMO, energy gap, electronegativity and electrophilicity index could be helpful to understand the various antimicrobial activities among these compounds. The antimicrobial activity of compound 6a was evaluated in vitro against Salmonella choleraesuis subsp. choleraesuis, Lactococcus lactis subsp. lactis and Saccharomyces cerevisiae by time-kill, and it was found that compound 6a exhibited significant microbiocidal activity against the three microorganisms.
- Ma, Yan-Long,Zhou, Ru-Jin,Zeng, Xing-Ye,An, Ya-Xiong,Qiu, Song-Shan,Nie, Li-Jun
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p. 226 - 234
(2014/03/21)
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- A protocol for accessing the β-azidation of α,β-unsaturated carboxylic acids
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This contribution reports the preparation and use of a new immobilized catalyst, PS-DABCOF (9), which has been specifically designed to access for the first time the efficient β-azidation of α,β-unsaturated carboxylic acids.
- Angelini, Tommaso,Bonollo, Simona,Lanari, Daniela,Pizzo, Ferdinando,Vaccaro, Luigi
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supporting information
p. 4610 - 4613
(2012/10/30)
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- Ring-opening of cyclic anhydrides using ionic liquids
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Four novel Bronsted acidic ionic liquids with two different acid sites on the imidazolium cations were synthesised and employed as catalysts and solvents for the ring-opening of cyclic anhydrides to synthesise half-esters. The results showed that these novel Bronsted acidic ionic liquids were efficient and recyclable. Good yields, short reaction times and mild reaction conditions were achieved.
- Jiang, Dong,Wang, Yuan Yuan,Xu, Yan Nan,Dai, Li Yi
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experimental part
p. 167 - 169
(2009/10/15)
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- Design, synthesis, and evaluation of aza-peptide Michael acceptors as selective and potent inhibitors of caspases-2, -3, -6, -7, -8, -9, and -10
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Aza-peptide Michael acceptors are a novel class of inhibitors that are potent and specific for caspases-2, -3, -6, -7, -8, -9, and -10. The second-order rate constants are in the order of 106 M-1 s-1. The aza-peptide Michael acceptor inhibitor 18t (Cbz-Asp-Glu-Val-AAsp-trans-CH=CH-CON(CH2-1-Naphth)2 is the most potent compound and it inhibits caspase-3 with a k2 value of 5620000 M-1 s-1. The inhibitor 18t is 13700, 190, 6.4, 594, 37500, and 173-fold more selective for caspase-3 over caspases-2, -6, -7, -8, -9, and -10, respectively. Aza-peptide Michael acceptors designed with caspase specific sequences are selective and do not show any cross reactivity with clan CA cysteine proteases such as papain, cathepsin B, and calpains. High-resolution crystal structures of caspase-3 and caspase-8 in complex with aza-peptide Michael acceptor inhibitors demonstrate the nucleophilic attack on C2 and provide insight into the selectivity and potency of the inhibitors with respect to the P1′ moiety.
- Ekici, ?zlem Do?an,Li, Zhao Zhao,Campbell, Amy J.,James, Karen Ellis,Asgian, Juliana L.,Mikolajczyk, Jowita,Salvesen, Guy S.,Ganesan, Rajkumar,Jelakovic, Stjepan,Grütter, Markus G.,Powers, James C.
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p. 5728 - 5749
(2008/04/18)
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- PROPENOYL HYDRAZIDES
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The present disclosure provides compositions for inhibiting proteases, methods for synthesizing the compositions, and methods of using the disclosed protease inhibitors. Aspects of the disclosure include a peptidyl propenoyl hydrazide compositions that inhibit proteases, for example cysteine proteases, either in vivoor in vitro.
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Page/Page column 34
(2008/06/13)
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- Ring opening of cyclic anhydrides: Synthesis of achiral half-esters using Lewis acids
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A rapid and high yield preparation of half-esters from cyclic anhydrides using alcohols and Lewis acids is described.
- Sabitha, Gowravaram,Srividya,Yadav
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p. 4015 - 4018
(2007/10/03)
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- 277. Structure and Chemistry of Malonylmethyl- and Succinyl-Radicals. The Search for Homolytic 1,2-Rearrangements
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Malonylmethyl radical I and its thioester analogue II were generated by standard photolytic and thermolytic methods from perester and bromo precursors.The structures of I and II were examined by ESR spectroscopy and found to exist in preferred conformations.However, no indication for their rearrangement by 1,2-shift of either an ethoxycarboxyl or (ethylthio)carbonyl group to the corresponding succinyl radicals III and IV, respectively, was found at temperatures below -40 deg C.At higher temperatures of up to 140 deg C, the search for malonylmethyl -> succinyl rearrangement was examined by thorough-product analysis of the perester decomposition.There is evidence for the rearrangement of the radical I to III by photolysis and of the radical II to IV by thermolysis at 130 deg C in chlorobenzene to only a small extent.
- Aeberhard, Urs,Keese, Reinhart,Stamm, Erich,Voegeli, Ulrich-Christian,Lau, Willy,Kochi, Jay Kazuo
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p. 2740 - 2759
(2007/10/02)
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