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• 587-65-5 N-chloroacetyl-aniline 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 62-53-3 aniline 

Downstream Products

• 1071565-00-8 C₁₂H₁₇N₃O*ClH 
• 20127-95-1 C₁₉H₂₃N₃O 
• 949324-81-6 C₂₀H₂₅N₃O 
• 684213-09-0 2-(4-(3-(5-fluoro-1H-indol-3-yl)propyl)piperazin-1-yl)-N-phenylacetamide 
• 40798-95-6 N-phenyl-2-piperazinylacetamide 
• 1393644-13-7 C₁₇H₂₅N₃O₃ 
• 1393643-07-6 C₁₆H₂₃N₃O₃ 
• 1393643-60-1 N-hydroxy-3-(4-phenylcarbamoylmethylpiperazin-1-yl)propionamide 
• 1226513-56-9 2-[4-(2-(phenylamino)-2-oxoethyl)piperazine-1-yl]-N-hydroxyacetamide 

Relevant academic research and scientific papers

Higher-Affinity Agonists of 5-HT1AR Discovered through Tuning the Binding-Site Flexibility

Discovery of high-affinity and high-selectivity agonists of 5-HT1AR has become very attractive due to their potential therapeutic effects on multiple 5-HT1AR-related psychological and neurological problems. On the basis of our previously designed lead compound FW01 (Ki = 51.9 nM, denoted as 9a in the present study), we performed large-scale molecular dynamics simulations and molecular docking operations on 5-HT1AR-9a binding. We found the flip-packing events for the headgroup of 9a, and we also found that its tail group could bind flexibly at the agonist-binding site of 5-HT1AR. By finely tuning the flip-packing phenomenon of the 9a headgroup and tuning the binding flexibility of 9a tail group, we virtually designed a series of new 9a derivatives through molecular docking operations and first-principles calculations and predicted that these newly designed 9a derivatives should be higher-affinity agonists of 5-HT1AR. The computational predictions on the new 9a derivatives have been confirmed by our wet-experimental studies as chemical synthesis, binding affinity assays, and agonistic-function assays. The consistency between our computational design and wet-experimental measurements has led to our discovery of higher-affinity agonists of 5-HT1AR, with ～50-fold increase in receptor-binding affinity and ～25-fold improvements in agonistic function. In addition, our newly designed 5-HT1AR agonists showed very high selectivity of 5-HT1AR over subtype 5-HT2AR and also over three subtypes of dopamine receptors (D1, D2, and D3). (Graph Presented).

Design, Synthesis, and Structure-Activity Relationship Studies of Novel Indolyalkylpiperazine Derivatives as Selective 5-HT1A Receptor Agonists

5-HT1A receptor (5-HT1AR) agonists have been implicated in the treatment of a variety of central nervous system (CNS) diseases such as depression and anxiety, et al. Based on our previously found compound FW01 (Ki = 51 ± 16 nM) obtained by virtual screening, a series of FW01 derivatives were designed and synthesized by the modification of the amide tail group as well as indole headgroup of FW01. SAR exploration found that amide tail group and indole headgroup play pivotal roles in determining the binding affinity and selectivity on dopamine and serotonin receptor subtypes. Among all tested compounds, 9_24 has a Ki value of 5 ± 0.6 nM with a good selectivity toward 5-HT1AR. The [35S] GTPγS assay showed that 9_24 is a full agonist toward 5-HT1AR with an EC50 value of 0.059 nM, which shows 266.2 and 146.4-fold selectivity to 5-HT2A and D3 respectively. Molecular dynamics simulations and molecular docking studies with 5-HT1AR-9_24 were performed to disclose the mechanism of its high activity and selectivity. Finally, a detailed stepwise 9_24 induced signal transduction mechanism of 5-HT1AR is proposed.

Design, synthesis, and evaluation of indolebutylamines as a novel class of selective dopamine D3 receptor ligands

A series of indolebutylamine derivatives were designed, synthesized, and evaluated as a novel class of selective ligands for the dopamine 3 receptor. The most potent compound 11q binds to dopamine 3 receptor with a Ki value of 124 nm and displays excellent selectivity over the dopamine 1 receptor and dopamine 2 receptor. Investigation based on structural information indicates that site S182 located in extracellular loop 2 may account for high selectivity of compounds. Interaction models of the dopamine 3 receptor-11q complex and structure-activity relationships were discussed by integrating all available experimental and computational data with the eventual aim to discover potent and selective ligands to dopamine 3 receptor.

The design and synthesis of 1,4-substituted piperazine derivatives as triple reuptake inhibitors

Novel 1,4-substituted piperazine derivatives 5, Series A and B were designed by fragment analysis and molecular modification of 4 selected piperazine-containing compounds which possess antidepressant activity. We synthesized new 39 analogues of Series A and 10 compounds of Series B, respectively. The antidepressant screening against DA, NE, and serotonin neurotransmitter uptake inhibition was carried out using the Neurotransmitter Transporter Uptake Assay Kit. The compounds in Series B showed relatively higher reuptake inhibitory activity for SERT, NET, and DAT than those in Series A. The length of spacer between the central piperazine core and the terminal phenyl ring substituted at the piperazine ring in Series B seems to exert an important role in the activity.

Design, synthesis and biological evaluation of hydroxamic acid derivatives as potential high density lipoprotein (HDL) receptor CLA-1 up-regulating agents

Trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) were reported in our recent publication as novel human high density lipoprotein (HDL) receptor CD36 and Lysosomal integral membrane protein-II Analogous-1 (CLA-1) up-regulators. As part of a