Anticholinesterase Activity of Compounds Related to Geneserine Tautomers. <i>N</i>-Oxides and 1,2-Oxazines

Yu, Qian‐sheng; Zhu, Xiaoxiang; Holloway, Harold W.; Whittaker, Noel F.; Brossi, A.; Greig, Nigel H.

doi:10.1021/jm010491d

Cited by 63 publications

(37 citation statements)

References 22 publications

(80 reference statements)

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“…We would like to point out that the problem of the initial formation of the cis-type relative stereochemistry at C3a and C8a in compound 6 is not obvious. As was already demonstrated by Brossi and Greig [2] in a similar system of physostigmine derivatives, the resulting compound might exist both in the cis-and transdiastereomeric forms, with the cis-form being responsible for 75 % of the population of stereoisomers. The preponderance of the cis form was also concluded from the calculations of the steric energy differences and was finally confirmed by the X-ray crystallography.…”

Section: Figmentioning

confidence: 56%

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The synthesis and the structure elucidation of N,O-diacetyl derivative of cyclic 3-hydroxymelatonin

et al. 2004

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Section: Figmentioning

confidence: 56%

“…Anticholinoesterases, such as physostigmine 1 (Scheme 1a), isolated from Calabar beans, along with its arylcarbamate analogues have proven to be promising drugs in the treatment of a variety of neurological disorders related to cholinergic transmission irregularities, e.g., Alzheimer's disease [2].…”

Section: Introductionmentioning

confidence: 99%

The synthesis and the structure elucidation of N,O-diacetyl derivative of cyclic 3-hydroxymelatonin

et al. 2004

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“…However, it has been withdrawn from the market, due to the hepatotoxicity of its metabolites [9]. As tacrine shows excellent binding for human AChE (hAChE) and human plasma BuChE (hpBuChE) with IC 50 s of 190 and 47 nM, respectively, there is current interest in making tacrine analogues and conjugates [10,11]. Galantamine, a natural product, is a reversible and selective AChE inhibitor.…”

Section: Introductionmentioning

confidence: 99%

“…It inhibits the degradation of ACh by binding in the AChE active site [8]. It demonstrated the following binding characteristics for heAChE and hpBuChE: IC 50 s of 800 and 7300 nM, respectively [11]. Donepezil is a reversible and selective AChE inhibitor.…”

Section: Introductionmentioning

confidence: 99%

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Insights into (S)-rivastigmine inhibition of butyrylcholinesterase (BuChE): Molecular docking and saturation transfer difference NMR (STD-NMR)

Bacalhau

Juan

Goth

et al. 2016

Bioorganic Chemistry

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a b s t r a c tRivastigmine is a very important drug prescribed for the treatment of Alzheimer's disease (AD) symptoms. It is a dual inhibitor, in that it inhibits both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). For our screening program on the discovery of new rivastigmine analogue hits for human butyrylcholinesterase (hBuChE) inhibition, we investigated the interaction of this inhibitor with BuChE using the complimentary approach of the biophysical method, saturation transfer difference (STD)-NMR and molecular docking. This allowed us to obtain essential information on the key binding interactions between the inhibitor and the enzyme to be used for screening of hit compounds. The main conclusions obtained from this integrated study was that the most dominant interactions were (a) H-bonding between the carbamate carbonyl of the inhibitor and the NH group of the imidazole unit of H434, (b) stacking of the aromatic unit of the inhibitor and the W82 aromatic unit in the choline binding pocket via p-p interactions and (c) possible CH/p interactions between the benzylic methyl group and the Nmethyl groups of the inhibitor and W82 of the enzyme.

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Highly Enantioselective and Diastereoselective Cycloaddition of Cyclopropanes with Nitrones and Its Application in the Kinetic Resolution of 2‐Substituted Cyclopropane‐1,1‐dicarboxylates

2007

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Trisoxazolines [1] have been applied widely in asymmetric catalysis [2] and molecular recognition. [3] In our efforts to develop superior catalysts that are cheap, readily accessible, air stable, and water tolerant, we designed and synthesized the pseudo-C 3 -symmetric trisoxazoline 1 b (Scheme 1) by the sidearm approach, and found that 1 b/Cu II promoted smoothly the highly enantioselective Friedel-Crafts reaction of indoles with arylidene malonates [4] and the Kinugasa reaction.[5] We also described tox/Co II -catalyzed [3+2] cycloaddition reactions between nitrones and alkylidene malonates in which the endo/exo selectivity could be controlled well by the reaction temperature. Thus, both cis and trans isoxazolidines could be prepared enantioselectively.[6] Herein, we report that the system tox/Ni II catalyzes the [3+3] cycloaddition of racemic 2-substituted cyclopropane-1,1-dicarboxylates with nitrones to provide ready access to optically active tetrahydro-1,2-oxazine derivatives with high diastereoselectivity and enantioselectivity. Furthermore, this reaction can be employed for the kinetic resolution [7] of 2-substituted cyclopropane-1,1-dicarboxylates to furnish these compounds in optically active form with excellent ee values.Tetrahydro-1,2-oxazine derivatives occur frequently in biologically active compounds [8] and are valuable synthetic intermediates.[9] Among the methods developed for the preparation of such compounds, [10] the [3+3] cycloaddition of donor-acceptor cyclopropanes with nitrones, pioneered by Kerr and co-workers, [11] is a particularly elegant approach. They found that nitrones 3 react smoothly with cyclopropanes 2 in the presence of Yb(OTf) 3 ·x H 2 O to give the cis isomers 4 diastereospecifically (see Table 1). Recently, Sibi et al. developed a highly efficient asymmetric version of this reaction. [12] They reported that nitrones react with cyclopropane-1,1-dicarboxylates to afford tetrahydro-1,2-oxazine derivatives with high enantioselectivity in the presence of dbfox/Ni II (10 mol %; dbfox = 4,6-dibenzofurandiyl-2,2-bisoxazoline). When 2-substituted cyclopropane-1,1-dicarboxylates were used as substrates, and the quantity of the catalyst was increased to 30 mol %, the reactions proceeded smoothly to give the products with high ee values but with low diastereoselectivities (the cis/trans ratio ranged from 1.0:1.4 to 1.0:0.8).Gratifyingly, we found that diethyl 2-phenylcyclopropane-1,1-dicarboxylate (2 a) reacted smoothly with nitrone 3 a to furnish the cycloaddition adduct in 99 % yield with excellent diastereoselectivity (d.r. > 99:1) in the presence of a catalytic amount of 1 b/Ni(ClO 4 ) 2 ·6 H 2 O. Further studies showed that ligands derived from iPr-box (box = bisoxazoline) influenced strongly both the enantioselectivity and diastereoselectivity of the reaction. The bisoxazoline 1 a without a pendant group gave the desired product with good diastereoselectivity (d.r. 97:3) but only 20 % ee (Table 1, entry 1). However, when a pyrid-2-yl or oxazolinyl group was introduced as a pend...

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Anticholinesterase Activity of Compounds Related to Geneserine Tautomers. N-Oxides and 1,2-Oxazines

Cited by 63 publications

References 22 publications

The synthesis and the structure elucidation of N,O-diacetyl derivative of cyclic 3-hydroxymelatonin

The synthesis and the structure elucidation of N,O-diacetyl derivative of cyclic 3-hydroxymelatonin

Insights into (S)-rivastigmine inhibition of butyrylcholinesterase (BuChE): Molecular docking and saturation transfer difference NMR (STD-NMR)

Highly Enantioselective and Diastereoselective Cycloaddition of Cyclopropanes with Nitrones and Its Application in the Kinetic Resolution of 2‐Substituted Cyclopropane‐1,1‐dicarboxylates

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