- Preparation method of N-alkoxy oxalyl alanine ester
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The invention discloses a preparation method of N-alkoxy oxalyl alanine ester, which comprises the following steps: (1) under the action of triphosgene and an organic alkali, carrying out an esterification reaction on alanine and an alcohol to obtain alanine ester hydrochloride; and (2) under the action of the organic alkali, carrying out an amidation reaction on the alanine ester hydrochloride obtained in the step (1) and oxalic ester, and after the reaction is finished, carrying out post-treatment to obtain the N-alkoxy oxalyl alanine ester. According to the preparation method, the triphosgene and the organic alkali are used as reaction additives, so that the use of toxic solvent benzene is avoided, the reaction time is shortened, the product purity and the reaction yield are high, and the preparation method is suitable for industrial production.
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Paragraph 0038-0039
(2019/12/02)
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- Enantioselective synthesis of α-secondary and α-tertiary piperazin-2- Ones and piperazines by catalytic asymmetric allylic alkylation
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The asymmetric palladium-catalyzed decarboxylative allylic alkylation of differentially N-protected piperazin-2- ones allows the synthesis of a variety of highly enantioenriched tertiary piperazine-2-ones. Deprotection and reduction affords the corresponding tertiary piperazines, which can be employed for the synthesis of medicinally important analogues. The introduction of these chiral tertiary piperazines resulted in imatinib analogues which exhibited comparable antiproliferative activity to that of their corresponding imatinib counterparts.
- Korch, Katerina M.,Eidamshaus, Christian,Behenna, Douglas C.,Stoltz, Brian M.,Nam, Sangkil,Horne, David
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supporting information
p. 179 - 183
(2015/02/05)
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- Evaluation of 1,2-dimethyl-3-hydroxy-4-pyridinecarboxylic acid and of other 3-hydroxy-4-pyridinecarboxylic acid derivatives for possible application in iron and aluminium chelation therapy
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Four new possible chelating agents for iron and aluminium, 1,2-dimethyl-3-hydroxy-4-pyridinecarboxylic acid (DT712), 3-hydroxy-1,2,6- trimethyl-4-pyridinecarboxylic acid, 2,6-dimethyl-3-hydroxy-4-pyridinecarboxylic acid, and 2-ethyl-3-hydroxy-1-methyl-4-pyridinecarboxylic acid, were synthesized, and their complex formation with Fe(III) and Al(III) was studied by potentiometry, UV-Vis, 1H NMR, and electrospray mass spectrometry (ESI-MS). Number, stoichiometry, and stability constants of metal-ligand complexes were obtained at 25 C in aqueous (Na)Cl 0.6 m. DT712 is the most promising hydroxypyridinecarboxylic acid considered so far for iron chelation therapy, as it forms the strongest Fe(III) complexes. This compound was further investigated to better clarify its possible behaviour in vivo with particular respect to iron chelation therapy. UV-Vis measurements were performed to determine the kinetics by which DT712 extracts Fe(III) from transferrin. DT712 resulted to have better kinetic properties than existing iron chelators. Ternary metal/DT712/citric acid complexes were studied by ESI-MS to check the competition with a typical low molecular weight ligand in the blood. The formation of only binary Fe(III)/DT712 and Al(III)/DT712 complexes (and ternary complexes in aged solutions), suggests that DT712 effectively compete with citric acid in the metal complexation. Standard reduction potentials of Fe(III)/DT712 complexes, and the kinetic constants of complex formation, were obtained by cyclic voltammetry. Accordingly, no redox cycling is expected to occur at in vivo conditions, and Fe(III)/DT712 complex formation should not be kinetically limited. On the basis of the present results, DT712 is proposed as candidate for iron chelation therapy.
- Dean, Annalisa,Ferlin, Maria Grazia,Cvijovic, Mirjana,Djurdjevic, Predrag,Dotto, Francesco,Badocco, Denis,Pastore, Paolo,Venzo, Alfonso,Di Marco, Valerio B.
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p. 520 - 528
(2013/11/19)
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- Synthesis, crystal structure and insecticidal activity of the optical active neonicotinoid analogues
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Eight novel neonicotinoid analogues 1-(2-tetrahydrofurfuryl)-5-substituted- 1,3,5-hexahydrotriazine-2-N-nitroimines 3a - 3h were synthesized, and their structures were characterized by 1H NMR, IR and elemental analysis. The stereostructure of 3a was determined by the single-crystal X-ray analysis, which exhibits a half-chair conformation and dihedral angle is 49.70° . The preliminary bioassay tests showed that all the title compounds exhibited good insecticide activities against Nilaparvata legen (N. legen).
- Xue, Sijia,Bu, Hongfei,Liu, Li,Xu, Xiao,Ma, Xubo
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scheme or table
p. 1011 - 1016
(2012/01/06)
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- Anthranilic acid based CCK1 receptor antagonists: Blocking the receptor with the same 'words' of the endogenous ligand
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The anthranilic acid diamides represent the more recent class of nonpeptide CCK1 receptor antagonists. This class is characterized by the presence of anthranilic acid, used as a molecular scaffold, and two pharmacophores selected from the C-terminal tetrapeptide of CCK. The lead compound coded VL-0395, endowed with sub-micromolar affinity towards CCK1 receptors, was characterized by the presence of Phe and 2-indole moiety at the C- and N-termini of anthranilic acid, respectively. Herein we describe the first step of the anthranilic acid C-terminal optimization using, instead of Phe, aminoacids belonging to the primary structure of CCK-8 and other not coded residues. Thus we demonstrate that the CCK1 receptor affinity depends on the nature of the aminoacidic side chain as well as that the free carboxy group of the alpha-aminoacids is crucial for the binding. The R enantiomers of the most active compounds represent the eutomers of this class of antagonists confirming thus the stereo preference of the receptor. Moreover this SAR study demonstrates that the receptor binding pocket, that host the aminoacidic side chain, results much more tolerant respect to that accommodating the indole ring. As a result, an appropriate variation of the aminoacidic side chain could provide a better CCK1 receptor affinity diorthosis.
- Lassiani, Lucia,Pavan, Michela V.,Berti, Federico,Kokotos, George,Markidis, Theodoros,Mennuni, Laura,Makovec, Francesco,Varnavas, Antonio
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experimental part
p. 2336 - 2350
(2009/09/05)
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- Evaluation of 2-methyl-3-hydroxy-4-pyridinecarboxylic acid as a possible chelating agent for iron and aluminium
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In view of a possible application to Fe and Al chelation therapy, 2-methyl-3-hydroxy-4-pyridinecarboxylic acid (DT2) was synthesised, and its complex formation, electrochemical and cytotoxic properties were studied. The complexing properties of DT2 towards Fe(iii) and Al(iii) were investigated in aqueous 0.6 m (Na)Cl at 25 °C by means of potentiometric titrations, UV-vis spectrophotometry, and 1H NMR spectroscopy. DT2 is a triprotic acid (H3L+) having pKa1 = 0.47, pKa2 = 5.64 and pKa3 = 11.18. The metal-ligand complexes observed in solution and their corresponding stability constants (logβ values) are the following: FeLH (19.38), FeL (16.01), FeLH-1 (12.28), FeL 2H2 (37.29), FeL3H3 (53.41), FeL3H2 (47.99), FeL3H (41.21) and FeL 3 (34.1); AlLH (17.43), AlL2H2 (33.74), AlL2H (27.6), AlL3H3 (48.72), AlL 3H2 (42.67), AlL3H (35.8) and AlL3 (27.92). The complex formation between DT2 and Fe(ii) was studied by UV-vis: the weak complex FeLH (logβ = 15.8) was detected. DT2 shows a lower complexation efficiency with Fe(iii) and Al(iii) than that of other available chelators, but higher than that of its non-methylated analogue 3-hydroxy-4-pyridinecarboxylic acid (DT0). The electrochemical behaviour of DT2 was investigated by means of cyclic voltammetry, indicating that the oxidation of the ligand proceeds through a two electron process with a CECE mechanism. Voltammetric curves suggest that the oxidation or the reduction of DT2 in vivo is unlikely. According to the thermodynamic data, also the Fe(iii)-DT2 complexes do not undergo redox cycling at physiological pH. Amperometric titrations of solutions containing Fe(iii) and DT2 at pH = 5 indicated the same Fe(iii): ligand stoichiometric ratio as calculated from potentiometric data. The toxicity of DT2 and of other simple hydroxypyridinecarboxylic acids was investigated in vitro and no cytotoxic activity was observed (IC50 > 0.1 mM) on cancer cell lines and also on primary human cells, following a three day exposure. The Royal Society of Chemistry.
- Dean, Annalisa,Ferlin, Maria Grazia,Brun, Paola,Castagliuolo, Ignazio,Badocco, Denis,Pastore, Paolo,Venzo, Alfonso,Bombi, G. Giorgio,Di Marco, Valerio B.
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p. 1689 - 1697
(2008/09/20)
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- Synthesis, selective aldose reductase inhibitory profile and antihyperglycaemic potential of certain parabanic acid derivatives
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Synthesis and aldose reductase inhibitory profile of certain parabanic acid derivatives 1a-p is described. Also, the antihyperglycaemic potential of these compounds was studied. The most active inhibitors in this series were compounds 1 g, 1p, and 1o which showed inhibitory activity, 36.6, 90 and 91% respectively, at concentration 1 × 10-4. Their IC50 were 2 × 10-6, 7.5 × 10-8 and 5 × 10-8, respectively. Compound 1o exhibited pronounced antihyperglycaemic effect.
- Nabil Aboul-Enein,El-Azzounya,Maklad,Attia,Wiese
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p. 329 - 350
(2007/10/03)
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- 1,2,3,4-TETRAHYDROQUINOXALINEDIONE DERIVATIVE
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A 1,2,3,4-tetrahydroquinoxalinedione derivative represented by the following formula (I) or salt thereof, an NMDA-glycine receptor and/or AMPA receptor antagonist or kainic acid neurotoxicity inhibitor containing the derivative or salt. In addition, a pharmaceutical composition comprising said compound and a pharmaceutically acceptable carrier: STR1 wherein the substituents are as described in the specification.
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- Alanine-derived Hosts Comprising a Roof-shaped Carbonimide Framework. Synthesis, Inclusion Formation and X-Ray Crystal Structures of Racemic and Optically Resolved Free Hosts, and their Crystalline Complexes with 3-Methylcyclohexanone
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A chiral crystalline host molecule derived from the amino acid alanine comprising a characteristic 9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboximide framework as an inclusion-promoting group has been synthesized in optically resolved and racemic forms and studied with regard to their inclusion behaviour.Dependent on the optical resolution state, this host forms crystalline inclusion compounds with a great variety of uncharged organic molecules ranging from protic dipolar to rather apolar compounds (78 different inclusion species) with the racemic host being more efficient.X-Ray crystal structures of the optically resolved and racemic uncomplexed host species and of their 1:1 inclusion complexes with 3-methylcyclohexanone are reported.The host hydroxy groups are always involved in O-H...O=C intramolecular hydrogen bonds.The crystal packings of both complexes are analogous, showing similar cell dimensions and space groups P21 and P21/a.Moreover, the two independent molecules in the resolved complex are almost related by a pseudo centre of symmetry.
- Weber, Edwin,Reutel, Christiane,Foces-Foces, Concepcion,Llamas-Saiz, Antonio L.
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p. 1455 - 1462
(2007/10/02)
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- Method of increasing the yield of legumes utilizing chloroacetyl-aminoacid ethyl esters
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A method of increasing the yield of legumes (soybeans) utilizing a compound of the formula STR1 wherein R is selected from the group consisting of --H, --CH3, --C2 H5 and --C3 H7.
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