- Synthesis, biological evaluation and molecular modeling studies of substitutedN-benzyl-2-phenylethanamines as cholinesterase inhibitors
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In this work, we report the synthesis of a series of derivatives ofN-benzyl-2-phenylethanamine which is the framework of norbelladine, the natural common precursor of the Amaryllidaceae alkaloids. These compounds were assessed in the inhibition of both AChE and BChE which are the enzymes responsible for the breakdown of acetylcholine and hence they constitute targets in the palliative treatment of Alzheimer's disease. In particular, brominated derivatives exhibited the lowest IC50values against AChE. Interestingly, the presence of iodine in one of the aromatic rings highly increased the inhibition of BChE compared to its analogues, with an IC50value similar to that of galantamine, which is the reference compound currently used in the treatment of AD. A possible mechanism of action for these compounds was determined by molecular modeling studies using combined techniques of docking and molecular dynamics simulations.
- Carmona-Viglianco, Florencia,Enriz, Ricardo D.,Feresin, Gabriela E.,Garro, Adriana,Kurina-Sanz, Marcela,Orden, Alejandro A.,Parravicini, Oscar,Zaragoza-Puchol, Daniel
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p. 9466 - 9476
(2020/06/17)
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- Chemoselective zinc/HCl reduction of halogenated β-nitrostyrenes: Synthesis of halogenated dopamine analogues
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A detailed account regarding the synthesis of 2- and 5-halogenated dopamine is given. The key step is a chemoselective reduction of a nitrostyrene by Zn/HCl at 0 °C. These conditions represent a simple, low-cost alternative to reduction by water-sensitive hydride donors and two-step procedures. Under these conditions, aryl fluoride, chloride, and bromide groups are stable. However, iodine undergoes significant reductive dehalogenation.
- Maresh, Justin J.,Ralko, Arthur A.,Speltz, Tom E.,Burke, James L.,Murphy, Casey M.,Gaskell, Zachary,Girel, Joann K.,Terranova, Erin,Richtscheidt, Conrad,Krzeszowiec, Mark
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supporting information
p. 2891 - 2894
(2015/02/02)
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- 4',5'-Dichloro-2',7'-dimethoxy-5(6)-carboxyfluorescein (JOE): Synthesis and spectral properties of oligonucleotide conjugates
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A convenient procedure for the preparation of the fluorescent dye 4',5'-dichloro-2',7'-dimethoxy-5(6)-carboxyfluorescein (JOE) is reported; the overall yield achieved starting from isovanillin is 10 times higher (40% vs 4%) compared to the known procedure. Isomers (5- and 6-) are easily chromatographically separable as pentafluorophenyl esters of 3′,6′-O-bis(cyclohexylcarbonyl) derivatives. Four non-nucleoside JOE phosphoramidites based on 5- and 6-isomers and flexible 6-aminohexanol (AH) or rigid 4-trans-aminocyclohexanol (ACH) linkers have been prepared and used for oligonucleotide labeling. Spectral and photophysical properties of 5′-JOE-modified oligonucleotides have been studied. Fluorescence quantum yield of the dye correlates with the nature of the linker (rigid vs flexible) and with the presence of dG nucleosides in close proximity to a JOE residue.
- Tsybulsky, Dmitry A.,Kvach, Maksim V.,Stepanova, Irina A.,Korshun, Vladimir A.,Shmanai, Vadim V.
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scheme or table
p. 977 - 984
(2012/03/26)
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- Highly stereoselective and efficient synthesis of the dopa analogue in pepticinnamin E via enantioselective hydrogenation of dehydroamino acids
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An efficient and new method was developed to prepare the dopa analogue 11 in natural pepticinnamin via catalytic hydrogenation of dehydroamino acids (DDAA) with a good yield and ee. Product 11 is a key intermediate towards the total synthesis of pepticinnamin E and its analogues. TUeBITAK.
- Sun, Dequn
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experimental part
p. 181 - 186
(2010/09/10)
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- Improved synthetic procedures for 4,7,2′,7′-tetrachloro- and 4′,5′-dichloro-2′,7′-dimethoxy-5(and 6)-carboxyfluoresceins
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Literature syntheses of 4,7,2′,7′-tetrachloro-5(and 6)-carboxyfluorescein ("5 and 6 TET") 1 and 4′,5′-dichloro-2′,7′-dimethoxy-5(and 6)-carboxyfluorescein ("5 and 6 JOE") 2 are reviewed, and new, preparatively useful methods are presented. A three-step synthesis of 1 was developed, which proved to be more efficient than the published seven step synthesis of this compound. The published synthesis of 2 also proved difficult to reproduce, and a better workup of the key intermediate 2-chloro-4-methoxy resorcinol was devised. Isolation of purified single isomers of both dyes is described.
- Lyttle, Matthew H.,Carter, Tim G.,Cook, Ronald M.
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- Aryl-substituted cycloalkanes and cycloalkenes and herbicidal use thereof
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Disclosed are herbicidal aryl substituted cycloalkyl and aryl substituted cycloalkenyl compounds, herbicidal compositions, and herbicidal use of the compounds and compositions. The aryl substituent is selected from substituted phenyl, unsubstituted or substituted five-membered heterocycle, and unsubstituted or substituted six-membered heterocycle.
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- Synthesis and in vitro evaluation of the Ras farnesyltransferase inhibitor pepticinnamin E
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A modularly built bisubstrate inhibitor, the natural product pepticinnamin E (shown on the right) was synthesized for the first time. In the case of in vitro assays it inhibits the enzyme farnesyltransferase with respect to both the peptide substrate and farnesylpyrophosohate (K1 = 30 and 8 μM, respectively). The inhibitory activity is decisively influenced by the central tripeptide unit and the absolute configuration of the non-proteinogenic amino acid incorporated therein.
- Hinterding, Klaus,Hagenbuch, Patrizia,Retey, Janos,Waldmann, Herbert
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p. 1236 - 1239
(2007/10/03)
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- Solid oral preparation containing a pyrrolidine derivative with a catechol group
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An oral solid preparation comprising an organic acid or its salt and a catechol compound. The catechol compound is, for example, a pyrrolidine derivative having a catechol group of the following general formula (I). It exhibits an improved absorbability in vivo. STR1
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- Comparative α- and β-adrenoceptor activity of 2- and 6-ring-chlorinated noradrenaline analogues
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The α- and β-adrenoceptor activity of the 2- and 6-ring-chlorinated analogues of noradrenaline (norepinephrine) were evaluated in vitro. The 2-chloro-substituted analogue exhibits a far greater affinity for β1-chronotropic receptors than the 6-chloro-substituted analogue, whereas no significant differences are apparent for their α-adrenergic affinities.
- Squier,Van der Schyf,Oliver,Venter
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p. 457 - 460
(2007/10/02)
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- 6-HALO-3-LOWER ALKYL-7,8-DIHYDROXY-1-PHENYL-2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPINES
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6-Halo-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepines whose structures have a lower alkyl substituted at the 3 or N-position have potent and often specific anti-Parkinsonism activity by means of their central dopaminergic effect. The lead compound of the series is 6-chloro-3-methyl-1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1H-3-benzazepin e as the base or its salts such as the hydrochloride, hydrobromide or methane sulfonate.
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- 2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPINE-7,8-DIONES
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Novel benzazepine derivatives having central and peripheral dopaminergic activity useful in treating Parkinson's and cardiovascular diseases. The compounds have additional use as intermediates for the synthesis of other benzazepines with similar useful properties. The 1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-dione derivatives are particularly useful.
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