155069-71-9Relevant articles and documents
2-(2-Hydroxyethyl)piperazine derivatives as potent human carbonic anhydrase inhibitors: Synthesis, enzyme inhibition, computational studies and antiglaucoma activity
Chiaramonte, Niccolò,Angeli, Andrea,Sgambellone, Silvia,Bonardi, Alessandro,Nocentini, Alessio,Bartolucci, Gianluca,Braconi, Laura,Dei, Silvia,Lucarini, Laura,Teodori, Elisabetta,Gratteri, Paola,Wünsch, Bernhard,Supuran, Claudiu T.,Romanelli, Maria Novella
, (2021/12/17)
Targeting Carbonic Anhydrases (CAs) represents a strategy to treat several diseases, from glaucoma to cancer. To widen the structure-activity relationships (SARs) of our series of piperazines endowed with potent human carbonic anhydrase (hCA) inhibition, a new series of chiral piperazines carrying a (2-hydroxyethyl) group was prepared. The Zn-binding function, the 4-sulfamoylbenzoyl moiety, was connected to one piperazine N-atom, while the other nitrogen was decorated with alkyl substituents. In analogy to the approach used for the synthesis of the previously reported series, the preparation of the new compounds started with (R)- and (S)-aspartic acid. A partial racemization occurred during the synthesis. In order to overcome this problem, other chemical strategies were investigated. The inhibitory activity of the new polar derivatives against four hCAs isoforms I, II, IV and IX using a stopped flow CO2 hydrase assay was determined. Some compounds showed potency in the nanomolar range and a preference for inhibiting hCA IX.
Preparation method of nitrogen-substituted aspartic acid
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Paragraph 0045; 0046; 0047; 0048, (2019/01/24)
The invention discloses a preparation method of nitrogen-substituted aspartic acid, the method comprises the following steps: providing a nitrogen-substituted aspartic acid compound with the structural formula as shown in the specification, wherein R1 is alkyl, and R2 is an amino protecting group; performing deprotection treatment on the nitrogen-substituted aspartic acid compound to obtain the nitrogen-substituted aspartic acid with the structural formula as shown in the specification, and the preparation method disclosed by the invention can be used for reducing the cost of preparing the nitrogen-substituted aspartic acid and enabling the nitrogen-substituted aspartic acid to be suitable for industrial production.
Rigidity versus Flexibility: Is This an Issue in σ1 Receptor Ligand Affinity and Activity?
Weber, Frauke,Brune, Stefanie,B?rgel, Frederik,Lange, Carsten,Korpis, Katharina,Bednarski, Patrick J.,Laurini, Erik,Fermeglia, Maurizio,Pricl, Sabrina,Schepmann, Dirk,Wünsch, Bernhard
, p. 5505 - 5519 (2016/07/06)
Stereoisomeric 2,5-diazabicyclo[2.2.2]octanes 14 and 15 were prepared in a chiral-pool synthesis starting from (S)- or (R)-aspartate. The key step in the synthesis was a Dieckmann-analogous cyclization of (dioxopiperazinyl)acetates 8, which involved trapping of the intermediate hemiketal anion with Me3SiCl. The σ1 affinity was tested using membrane preparations from animal (Guinea pig) and human origin. The binding of bicyclic compounds was analyzed by molecular dynamics simulations based on a 3D homology model of the σ1 receptor. The good correlation between Ki values observed in the σ1 assays and calculated free binding energy, coupled with the identification of four crucial ligand/receptor interactions, allowed the formulation of structure-affinity relationships. In an in vitro antitumor assay with seven human tumor cell lines, the bicyclic compounds inhibited selectively the growth of the cell line A427, which is due to induction of apoptosis. In this assay, the compounds behave like the known σ1 receptor antagonist haloperidol.
