617-27-6Relevant articles and documents
Preparation method of N-alkoxy oxalyl alanine ester
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Paragraph 0038-0039, (2019/12/02)
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.
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
Dean, Annalisa,Ferlin, Maria Grazia,Cvijovic, Mirjana,Djurdjevic, Predrag,Dotto, Francesco,Badocco, Denis,Pastore, Paolo,Venzo, Alfonso,Di Marco, Valerio B.
, p. 520 - 528 (2013/11/19)
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.
Anthranilic acid based CCK1 receptor antagonists: Blocking the receptor with the same 'words' of the endogenous ligand
Lassiani, Lucia,Pavan, Michela V.,Berti, Federico,Kokotos, George,Markidis, Theodoros,Mennuni, Laura,Makovec, Francesco,Varnavas, Antonio
experimental part, p. 2336 - 2350 (2009/09/05)
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.
