- Synthesis of New Tyrosol-Based Phosphodiester Derivatives: Effect on Amyloid β Aggregation and Metal Chelation Ability
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Alzheimer's disease (AD) is a multifactorial pathology that requires multifaceted agents able to address its peculiar nature. Increasing evidence has shown that aggregation of amyloid β (Aβ) and oxidative stress are strictly interconnected, and their modu
- Romanucci, Valeria,Giordano, Maddalena,De Tommaso, Gaetano,Iuliano, Mauro,Bernini, Roberta,Clemente, Mariangela,Garcia-Vi?uales, Sara,Milardi, Danilo,Zarrelli, Armando,Di Fabio, Giovanni
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p. 1172 - 1183
(2021/02/01)
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- Pyrazine compounds with multiple effects and preparation method thereof
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The invention relates to pyrazine compounds, stereoisomers, tautomers and pharmaceutically acceptable salts of the pyrazine compounds. The pyrazine compounds can be used for treating Alzheimer's disease, Parkinson's disease, Huntington's disease, frontal temporal dementia (FTD), vascular dementia, HIV-related dementia, multiple sclerosis, progressive spinal cord lateral sclerosis, Friedel-Crafts ataxia, neuropathic pain or glaucoma and other neurodegenerative diseases, diabetes mellitus and related diabetic complications, inflammation, oxidative damage and mitochondria-related diseases.
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Paragraph 0056-0057; 0060-0061
(2020/11/01)
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- Pyrazine compound and preparation method thereof
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The invention relates to a pyrazine compound, a stereoisomer, a tautomer and a pharmaceutically acceptable salt thereof, wherein the pyrazine compound, the stereoisomer, the tautomer and the pharmaceutically acceptable salt thereof can treat Alzheimer's disease, Parkinson's disease, Huntington's disease, frontal temporal dementia (FTD), vascular dementia, HIV-related dementia, multiple sclerosis,progressive spinal cord lateral sclerosis, Friedel-Crafts ataxia, neuropathic pain or glaucoma and other neurodegenerative diseases, diabetes mellitus and related diabetic complications, inflammations, oxidative damage and mitochondria-related diseases.
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Paragraph 0060; 0063-0064
(2020/11/09)
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- Application of pyrazine compound in preparation of drugs
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The invention relates to an application of a pyrazine compound in preparation of drugs. The drugs can be used for treating neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, frontotemporal dementia (FTD), vascular dementia, HIV-related dementia, multiple sclerosis, progressive lateral sclerosis, Friedreich's ataxia, neuropathic pain or glaucoma, inflammation, oxidative damage, and mitochondrial-related diseases.
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Paragraph 0063; 0066-0067
(2020/10/30)
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- Deoxyfluorination with CuF2: Enabled by Using a Lewis Base Activating Group
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Deoxyfluorination is a primary method for the formation of C?F bonds. Bespoke reagents are commonly used because of issues associated with the low reactivity of metal fluorides. Reported here is the development of a simple strategy for deoxyfluorination, using first-row transition-metal fluorides, and it overcomes these limitations. Using CuF2 as an exemplar, activation of an O-alkylisourea adduct, formed in situ, allows effective nucleophilic fluoride transfer to a range of primary and secondary alcohols. Spectroscopic investigations have been used to probe the origin of the enhanced reactivity of CuF2. The utility of the process in enabling 18F-radiolabeling is also presented.
- Bode, Bela E.,Chabbra, Sonia,Champion, Sue,Dawson, Daniel M.,Sood, D. Eilidh,Sutherland, Andrew,Watson, Allan J. B.
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supporting information
p. 8460 - 8463
(2020/04/10)
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- A deprotection procedure using SO3H silica gel to remove non-silyl protecting groups
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Protecting groups are indispensable in organic synthesis and there is a great need for a variety of deprotection methods. Here, we investigated the scope of the application of a deprotection procedure using SO3H silica gel, which we have previously reported as a desilylation procedure. Under these conditions, -OMOM, -OSEM, -OTHP, and -OAc groups and dimethyl acetal were cleaved. Pivaloyloxy, benzyloxy and methoxy carbonyl groups remained intact and selective deprotection of TBS groups in the presence of other protecting groups was accomplished. We succeeded in cleaving an acetyl group on a secondary alcohol in a highly polar nortropine derivative. Our findings here provide another deprotection option and would be helpful in the synthesis of multifunctional compounds.
- Karaki, Fumika,Kuwada, Miki,Tajiri, Saki,Kanda, Misaki,Yanai, Mari,Kamimura, Mitsuhiro,Itoh, Kennosuke,Fujii, Hideaki
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supporting information
p. 212 - 220
(2019/05/06)
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- Tandem Oxidative Dearomatizing Spirocyclizations of Propargyl Guanidines and Ureas
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Treatment of propargyl ureas or guanidines with iodosobenzene diacetate results in an oxidative tandem amination/etherification dearomatizing spirocyclization. This transformation leads directly to the complete framework of the Leucetta alkaloids, spiroca
- Singh, Ravi P.,Das, Jayanta,Yousufuddin, Muhammed,Gout, Delphine,Lovely, Carl J.
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supporting information
p. 4110 - 4113
(2017/08/15)
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- Synthesis and biological evaluation of analogs of AAL(S) for use as ceramide synthase 1 inhibitors
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A convergent synthesis to access hydrophobic tail analogs and head group modifications of AAL(S) is described. The analogs synthesised were evaluated for their ability to inhibit ceramide synthase 1 and for their cytotoxicity in K562 cells. Our results ha
- Toop, Hamish D.,Don, Anthony S.,Morris, Jonathan C.
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supporting information
p. 11593 - 11596
(2015/12/08)
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- Stereoselective synthesis of bioactive natural spiroacetals aculeatins A and B
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The stereoselective synthesis of two naturally occurring bioactive spiroacetals, aculeatins A and B has been accomplished using 1-tetradecanal as the starting material. The sequence introduces diastereoselective iodine-induced electrophilic cyclization an
- Das, Biswanath,Krishnaiah, Martha,Sudhakar, Chithaluri
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scheme or table
p. 2303 - 2305
(2010/07/04)
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- A novel, chemoselective and efficient microwave-assisted deprotection of silyl ethers with Selectfluor
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A novel microwave-assisted, chemoselective and efficient method for the cleavage of silyl ethers (aliphatic and aromatic) catalyzed by Selectfluor is reported. A wide range of TBS-, TIPS-, and TBDPS-protected alkyl silyl ethers can be chemoselectively cleaved in high yield in the presence of aryl silyl ethers. The chemoselective deprotection of phenolic TBS ethers, and not the TIPS- or TBDPS-protected phenolic ethers, and the deprotection of silyl esters were also achieved under these reaction conditions. In addition, the transetherification and etherification of benzylic hydroxy groups in alcoholic solvents is observed.
- Shah, Syed Tasadaque A.,Singh, Surendra,Guiry, Patrick J.
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experimental part
p. 2179 - 2182
(2009/07/01)
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- Synthetic libraries of tyrosine-derived bacterial metabolites
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The preparation of a collection of 131 small molecules, reminiscent of families of long chain N-acyl tyrosines, enamides and enol esters that have been isolated from heterologous expression of environmental DNA (eDNA) in Escherichia coli, is reported. The synthetic libraries of N-acyl tyrosines and their 3-keto counterparts were prepared via solid-phase routes, whereas the enamides and enol esters were synthesized in solution-phase.
- Georgiades, Savvas N.,Clardy, Jon
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supporting information; experimental part
p. 3117 - 3121
(2009/04/03)
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- NITROGEN-CONTAINING HETEROCYCLYL KETONES AND METHODS OF USE
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Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
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Page/Page column 148
(2008/12/08)
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- The chemoselective and efficient deprotection of silyl ethers using trimethylsilyl bromide
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An efficient and chemoselective cleavage of silyl ethers (primary, secondary and aromatic) by using catalytic quantities of trimethylsilyl bromide (TMSBr) in methanol is reported. A wide range of alkyl silyl ethers such as TBS, TIPS, and TBDPS can be chemoselectively cleaved in high yield in the presence of aryl silyl ethers. The deprotection of silyl esters was also achieved employing catalytic quantities of TMSBr. The Royal Society of Chemistry 2008.
- Shah, Syed Tasadaque A.,Guiry, Patrick J.
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experimental part
p. 2168 - 2172
(2009/02/01)
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- TX-2152: A conformationally rigid and electron-rich diyne analogue of FTY720 with in vivo antiangiogenic activity
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We designed FTY720 analogues with conformationally rigid and electron-rich acetylenic chains as antiangiogenic agents (the monoyne 1: TX-2148, the diyne 2: TX-2152, the triyne 3: TX-2256). Molecular orbital (MO) calculations of our designed acetylenic ana
- Nakayama, Shinichi,Uto, Yoshihiro,Tanimoto, Kanako,Okuno, Yasuhiro,Sasaki, Yuki,Nagasawa, Hideko,Nakata, Eiji,Arai, Ken,Momose, Kaori,Fujita, Tetsuro,Hashimoto, Toshihiro,Okamoto, Yasuko,Asakawa, Yoshinori,Goto, Satoru,Hori, Hitoshi
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experimental part
p. 7705 - 7714
(2009/04/06)
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- Syntheses of (-)-oleocanthal, a natural NSAID found in extra virgin olive oil, the (-)-deacetoxy-oleuropein aglycone, and related analogues
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(Chemical Equation Presented) Phenolic compounds extracted from extra virgin olive oil have attracted considerable recent attention. One of the components, (-)-oleocanthal (1), an inhibitor of the COX-1 and COX-2 enzymes, possesses similar potency as the NSAID ibuprofen. In this, a full account, we disclose the first- and now second-generation syntheses of both enantiomers of the oleocanthals, as well as the first synthesis of the closely related (-)-deacetoxy-oleuropein aglycone and a series of related analogues for structure activity studies. To demonstrate the utility of the second-generation synthesis, multigram quantities of (-)-oleocanthal were prepared in 10 steps (14% overall yield) from commercially available D-lyxose.
- Smith III, Amos B.,Sperry, Jeffrey B.,Han, Qiang
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p. 6891 - 6900
(2008/02/11)
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- Rapid, acid-mediated deprotection of silyl ethers using microwave heating
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Microwave heating of triethylsilyl (TES)- and tert-butyldimethylsilyl (TBS)-protected 1° and 2° alcohols in a mixture of equal parts acetic acid, tetrahydrofuran (THF), and water allows deprotection in as little as 5 min. tert-butyldiphenylsilyl (TBDPS)- and triisopropylsilyl (TIPS)-protected alcohols and silyl-protected phenols are stable in these conditions. Thus, selective deprotection of TES- and TBS-protected alcohols in the presence of TIPS or TBDPS ethers is possible. Similarly, alkyl silyl ethers can be deprotected in the presence of aryl silyl ethers. Copyright Taylor & Francis Group, LLC.
- Crouch,Williams, Anna
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p. 959 - 964
(2007/10/03)
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- Synthesis of methyl 1-O-(4-hydroxymethamphetaminyl)-α-D- glucopyranouronate
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For the purpose of the direct characterization of the intact conjugated form in the urine of a methamphetamine (MA) abuser, 4-hydroxymethamphetamine (4-OHMA) glucuronate, corresponding to one of the metabolites of MA, was synthesized from the commercially available methyl 4-hydroxyphenylacetate.
- Nakajima, Rika,Ono, Machiko,Aiso, Sadakazu,Akita, Hiroyuki
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p. 684 - 687
(2007/10/03)
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- Efficient chemoselective deprotection of silyl ethers using catalytic 1-chloroethyl chloroformate in methanol
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Fast and chemoselective desilylation of silyl-protected alcohols was achieved using a catalytic amount of 1-chloroethyl chloroformate in methanol. With a minimal amount of 1-chloroethyl chloroformate as the source for anhydrous HCl, extremely efficient cleavage of silyl ethers of primary and secondary alcohols was accomplished, and chemoselective deprotection of one silyl ether in the presence of another silyl or other acid-labile group was possible through controlling the amount of the chloroformate and reaction time.
- Yeom, Chang-Eun,Kim, Young Jong,Lee, So Young,Shin, Yong Je,Kim, B. Moon
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p. 12227 - 12237
(2007/10/03)
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- PHENETHANOLAMINE DERIVATIVES
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The present invention relates to novel compounds of formula (I), or a salt, solvate, or physiologically functional derivative thereof, to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases.
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Page/Page column 61
(2010/02/07)
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- Synthesis of long-chain fatty acid enol esters isolated from an environmental DNA clone
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(Matrix presented) Long-chain fatty acid enol ester 1 is the major metabolite of a new family of small molecules isolated from the heterologous expression of environmentally derived DNA. A versatile synthesis of 1, in which an aromatic acetaldehyde is O-a
- Brady, Sean F.,Clardy, Jon
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p. 121 - 124
(2007/10/03)
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- Deprotection of silyl ethers using ZnBr2 and H2O in CH2Cl2
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TES- and TBS-protected alcohols undergo deprotection upon treatment with excess ZnBr2 and water in CH2Cl2 at 44-50°C. TIPS-protected alcohols also undergo deprotection but at slower rates. TBDPS-protected alcohols and silyl-protected phenols are unreactive under these conditions, allowing for selective deprotection of differentially-protected bis-silyl ethers.
- Crouch, R.David,Polizzi, Joanna M.,Cleiman, Rebecca A.,Yi, Jihae,Romany, Candice A.
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p. 7151 - 7153
(2007/10/03)
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- Selective deprotection of either alkyl or aryl silyl ethers from aryl, alkyl bis-silyl ethers
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A pair of complementary methods was developed using CeCl3·7H2O/CH3CN and LiOH/DMF to selectively deprotect alkyl and aryl silyl ethers, respectively, from the corresponding bis-silyl ethers in excellent yields.
- Ankala, Sudha V.,Fenteany, Gabriel
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p. 4729 - 4732
(2007/10/03)
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- Selective deprotection of alkyl t-butyldimethylsilyl ethers in the presence of aryl t-butyldimethylsilyl ethers
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Alkyl TBS ethers can be selectively cleaved in high yield in the presence of aryl TBS ethers employing either in situ generated hydrogen chloride or hydrogen iodide.
- Grieco, Paul A.,Markworth, Christopher J.
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p. 665 - 666
(2007/10/03)
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- Selective deprotection of alkyl vs. aryl silyl ethers
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Alkyl silyl ethers, in particular t-butyldimethylsilyl derivatives, can be selectively cleaved in high yields over aryl silyl ethers using small percentage of I2 in MeOH at ambient temperatures.
- Lipshutz, Bruce H.,Keith, John
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p. 2495 - 2498
(2007/10/03)
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- Dose-response relations for unnatural amino acids at the agonist binding site of the nicotinic acetylcholine receptor: Tests with novel side chains and with several agonists
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Structure-function relations in the nicotinic acetylcholine receptor are probed using a recently developed method based on chemical synthesis of nonsense suppressor tRNAs with unnatural amino acid residues, site-directed incorporation at nonsense codons in Xenopus laevis oocytes, and electrophysiological measurements. A broad range of unnatural amino acids, as many as 14 at a given site, are incorporated at three sites, α93, α190, and α198, all of which are tyrosine in the wild-type receptor and are thought to contribute to the agonist binding site. Confirming and expanding upon earlier studies using conventional mutagenesis, the three tyrosines are shown to be in substantially different structural microenvironments. In particular, a crucial role is established for the hydroxyl group of α-Tyr93, whereas a variety of substituents are functional at the analogous position of αTyr198. Interestingly, consideration of three different agonists (acetylcholine, nicotine, and tetramethylammonium) does not discriminate between these two best-characterized binding site residues. In addition, double-mutation studies establish the independent effects of mutations at the pore region (second transmembrane region) and at the agonist binding site, and this observation leads to a novel strategy for adjusting EC50 values. These results establish the broad generality and great potential of the unnatural amino acid methodology for illuminating subtle structural distinctions in neuroreceptors and related integral membrane proteins.
- Kearney, Patrick C.,Nowak, Mark W.,Zhong, Wenge,Silverman, Scott K.,Lester, Henry A.,Dougherty, Dennis A.
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p. 1401 - 1412
(2007/10/03)
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- Selective removal of phenolic and alcoholic silyl ethers
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Potassium carbonate/Kriptofix 222 and pyridinium p-toluenesulfonate or BF3-etherate have been found to remove the tert-butyldimethylsilyl group from phenolic and alcoholic silyl ethers, respectively. This methodology should find wide applicability in complex organic synthesis.
- Prakash, Chandra,Saleh, Samir,Blair, Lan A.
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p. 7565 - 7568
(2007/10/02)
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- SELECTIVE DEPROTECTION OF ALCOHOLIC AND PHENOLIC SILYL ETHERS
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Hydrofluoric acid and tetrabutylammonium fluoride will selectively deprotect alcoholic and phenolic silyl ethers respectively.
- Collington, Eric W.,Finch, Harry,Smith, Ian J.
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p. 681 - 684
(2007/10/02)
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