- Chiral arylideneaminoimidazolidin-4-ones: Green synthesis and isomerisation mechanism in solution
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A green and eco-friendly synthetic approach of pure 2,5-disubstituted 3-arylideneaminoimidazolidin-4-ones is developed using water as the solvent. These new chiral arylideneaminoimidazolidin-4-one derivatives were obtained diastereoselectively in high ove
- Bouzayani, Nadia,Marque, Sylvain,Kacem, Yakdhane,Kra?em, Jamil,Bourdreux, Flavien,Marrot, Jér?me,Ben Hassine, Béchir
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p. 4777 - 4786
(2019/03/26)
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- Fragment Linking and Optimization of Inhibitors of the Aspartic Protease Endothiapepsin: Fragment-Based Drug Design Facilitated by Dynamic Combinatorial Chemistry
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Fragment-based drug design (FBDD) affords active compounds for biological targets. While there are numerous reports on FBDD by fragment growing/optimization, fragment linking has rarely been reported. Dynamic combinatorial chemistry (DCC) has become a powerful hit-identification strategy for biological targets. We report the synergistic combination of fragment linking and DCC to identify inhibitors of the aspartic protease endothiapepsin. Based on X-ray crystal structures of endothiapepsin in complex with fragments, we designed a library of bis-acylhydrazones and used DCC to identify potent inhibitors. The most potent inhibitor exhibits an IC50value of 54 nm, which represents a 240-fold improvement in potency compared to the parent hits. Subsequent X-ray crystallography validated the predicted binding mode, thus demonstrating the efficiency of the combination of fragment linking and DCC as a hit-identification strategy. This approach could be applied to a range of biological targets, and holds the potential to facilitate hit-to-lead optimization.
- Mondal, Milon,Radeva, Nedyalka,Fanlo-Virgós, Hugo,Otto, Sijbren,Klebe, Gerhard,Hirsch, Anna K. H.
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supporting information
p. 9422 - 9426
(2016/08/05)
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- In situ deprotection and incorporation of unnatural amino acids during cell-free protein synthesis
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The S30 extract from E. coli BL21 Star (DE3) used for cell-free protein synthesis removes a wide range of α-amino acid protecting groups by cleaving α-carboxyl hydrazides; methyl, benzyl, tert-butyl, and adamantyl esters; tert-butyl and adamantyl carboxamides; α-amino form-, acet-, trifluoroacet-, and benzamides and sidechain hydrazides and esters. The free amino acids are produced and incorporated into a protein under standard conditions. This approach allows the deprotection of amino acids to be carried out in situ to avoid separate processing steps. The advantages of this approach are demonstrated by the efficient incorporation of the chemically intractable (S)-4-fluoroleucine, (S)-4,5- dehydroleucine, and (2S,3R)-4-chlorovaline into a protein through the direct use of their respective precursors, namely, (S)-4-fluoroleucine hydrazide, (S)-4,5-dehydroleucine hydrazide, and (2S,3R)-4-chlorovaline methyl ester. These results also show that the fluoroand dehydroleucine and the chlorovaline are incorporated into a protein by the normal biosynthetic machinery as substitutes for leucine and isoleucine, respectively. Copyright
- Arthur, Isaac N.,Hennessy, James E.,Padmakshan, Dharshana,Stigers, Dannon J.,Lesturgez, Stéphanie,Fraser, Samuel A.,Liutkus, Mantas,Otting, Gottfried,Oakeshott, John G.,Easton, Christopher J.
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supporting information
p. 6824 - 6830
(2013/06/26)
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- Synthesis of novel 1-[(1-ethoxymethylene)amino]imidazol-5(4H)-ones and 1,2,4-triazin-6(5H)-ones from optically active α-aminocarboxylic acid hydrazides
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New derivatives of 1-[(1-ethoxymethylene)amino]imidazol-5(4H)-one and 1,2,4-triazin-6(5H)-one were synthesized via reactions of optically active α-aminocarboxylic acid hydrazides and triethyl orthoesters in xylene. The factors influencing the formation of the unexpected five-membered products and attempts to elucidate the mechanism are discussed.
- Kudelko, Agnieszka,Zieliński, Wojciech,Jasiak, Karolina
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supporting information
p. 4637 - 4640
(2013/08/23)
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- Synthesis and Antitubercular Activity of Novel Amino Acid Derivatives
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In this work, 17 new N-acylhydrazone derivatives of amino acids have been evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. The compounds 8b, 8e, 8f, 9a-d, and 10c exhibited an important minimum inhibitory concentration activity between 12.5 and 50μg/mL, which can be compared with that of the tuberculostatic drug d-cycloserine (20μg/mL). In this work 17 new N-acylhydrazone derivatives of amino acids have been evaluated for their in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv. Eight compounds were non-cytotoxic and exhibited an important MIC activity between 12.5 and 50μg/mL, which can be compared with that of the tuberculostatic drug d-cycloserine (20μg/mL).
- Da Costa, Cristiane F.,Pinheiro, Alessandra C.,De Almeida, Mauro V.,Lourenco, Maria C.S.,De Souza, Marcus V.N.
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experimental part
p. 216 - 222
(2012/04/23)
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- Sandwich structure of a ruthenium porphyrin and an amino acid hydrazide for probing molecular chirality by circular dichroism
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Owing to the strong Lewis acidity of ruthenium porphyrins, a commercial carbonyl ruthenium porphyrin and an amino acid hydrazide can assemble into a sandwich structure. The nature of such a structure is diagnostic of the absolute configuration of the amino acid by circular dichroism.
- Liang, Qing-Feng,Liu, Juan-Juan,Chen, Jian
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experimental part
p. 3987 - 3991
(2011/08/09)
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- Synthesis, characterization, spectral studies, biocidal activities of Fe(III), Co(II), Zn(II), Cd(II), Y(III), and In(III) complexes of schiff base derived from l-phenylalanine
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2-Amino-3-phenyl-propionic acid hydrazide (APPAH) (1 ) has been prepared by reacting earlier reported compound 2-amino-3-phenyl-propionic acid methyl ester (APPAME) with hydrazine hydrate. Schiff base 2((4-methoxy-bezylidene)-aminoJ-3- phenyl-propionic ac
- Salunke,Filmwala,Kamble
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supporting information; experimental part
p. 1243 - 1248
(2012/04/10)
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