155069-71-9

Upstream product

• 100-52-7 benzaldehyde 
• 14358-33-9 dimethyl (R)-2-aminobutanedioate hydrochloride 
• 6384-18-5 dimethyl D-aspartate 
• 100-39-0 benzyl bromide 
• 1584725-20-1 C₁₃H₁₅NO₄ 
• 32213-95-9 dimethyl L-aspartate hydrochloride 

Downstream Products

• 155069-72-0 Dimethyl D-N-(9-phenylfluoren-9-yl)-N-benzylaspartate 
• 1584725-28-9 methyl (R)-2-[1-benzyl-4-(cyclohexylmethyl)-3,6-dioxopiperazin-2-yl]acetate 
• 1584725-34-7 (R)-2-[1-benzyl-4-(cyclohexylmethyl)piperazin-2-yl]ethanol 
• 887470-75-9 (R)-2-(1-benzylpiperazin-2-yl)ethanol 
• 887470-76-0 (R)-methyl 2-(1-benzyl-3,6-dioxopiperazin-2-yl)acetate 
• 1389332-30-2 C₂₁H₂₉N₅O₇ 
• 887470-77-1 dimethyl N-benzyl-D-aspartate hydrochloride 

Relevant academic research and scientific papers

2-(2-Hydroxyethyl)piperazine derivatives as potent human carbonic anhydrase inhibitors: Synthesis, enzyme inhibition, computational studies and antiglaucoma activity

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

The invention discloses a preparation method of nitrogen-substituted aspartic acid, a nitrogen-substituted aspartic acid compound has the structural formula as shown in the specification, wherein R1 is alkyl, and R2 is an amino protecting group, and the preparation method can be used for preparation of the nitrogen-substituted aspartic acid from the nitrogen-substituted aspartic acid compound so as to reduce the cost of preparing the nitrogen-substituted aspartic acid and enables the nitrogen-substituted aspartic acid to be suitable for industrial production.

Preparation method of nitrogen-substituted aspartic acid

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.

Stereoselective synthesis of conformationally restricted KOR agonists based on the 2,5-diazabicyclo[2.2.2]octane scaffold

It has been postulated that the KOR affinity depends on the dihedral angle of the ethylenediamine pharmacophore. Herein, 2,5-diazabicyclooctanes bearing a pyrrolidino moiety in the 7-position were envisaged to study KOR agonists with a conformationally rigid ethylenediamine pharmacophore and thus a defined N(pyrrolidine)-C7-C1-N2 dihedral angle. The first approach with an intramolecular addition at the chiral sulfinylimines 9 failed to give bicyclic products. The key step in the second approach was a Dieckmann analogous cyclization providing mixed methyl silyl ketals 11a-e as key intermediates. The highest KOR affinity was found for the 2,5-dibenzyl substituted derivatives (S,R,S)-16a (Ki = 31 nM) and (R,S,R)-16a (Ki = 74 nM) with the pyrrolidine ring oriented towards N-5. The high KOR affinity of (S,R,S)-16a is unexpected, since the KOR pharmacophoric ethylenediamine system adopts a dihedral angle of about 160°, which is quite different from the angle of the energetically most favored conformer of the flexible and potent KOR agonist 2. (S,R,S)-16a represents a KOR agonist with moderate selectivity over MOR (8-fold) and DOR (5-fold), but high selectivity over both σ receptor subtypes. In the [35S]GTPγS assay (S,R,S)-16a reacted as a full KOR agonist with an EC50 value of 240 nM.

Rigidity versus Flexibility: Is This an Issue in σ1 Receptor Ligand Affinity and Activity?

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.

Synthesis, pharmacological evaluation, and σ1 receptor interaction analysis of hydroxyethyl substituted piperazines

Starting from (S)- or (R)-aspartate, three synthetic strategies were explored to prepare hydroxyethyl substituted piperazines with different substituents at the N-atoms. σ receptor affinity was recorded using receptor material from both animal and human o

AZABENZOXAZOLES FOR THE TREATMENT OF CNS DISORDERS

The present invention relates to a7 nicotinic receptor agonists of formula (la) or (lb) as described herein and to a method for treating disorders of the Central Nervous System (CNS) and other disorders in a mammal, including a human, by administering to the mammal an a7 nicotinic receptor agonist of formula (la) or (lb). It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier and a CNS-penetrant a7nicotinic receptor agonist of formula (la) or (lb).

2,3-Pyrrolidinedicarboxylates as Neurotransmitter Conformer Mimics: Enantioselective Synthesis via Chelation-Controlled Enolate Alkylation

Conformationally restricted analogs of naturally-occurring amino acids can serve in a variety of ways as protein structure/function probes.A diastereo- and enantioselective synthesis of the four stereoisomers of 2,3-pyrrolidinedicarboxylic acid (an analog