23145-91-7

Usage

Chemical Properties

Colorless liquid

InChI:InChI=1/C11H15ClN2/c12-11-3-1-2-10(8-11)9-14-6-4-13-5-7-14/h1-3,8,13H,4-7,9H2/p+2

Upstream product

• 110-85-0 piperazine 
• 620-20-2 1-Chloro-3-chloromethyl-benzene 
• 766-80-3 1-bromomethyl-3-chlorobenzene 
• 1158547-02-4 ClH*C₁₁H₁₅ClN₂ 
• 305860-09-7 4-(3-chlorobenzyl)-piperazine-1-carboxylic acid tert-butyl ester 

Downstream Products

• 739328-89-3 3-[4-(3-Chloro-benzyl)-piperazin-1-yl]-propan-1-ol 
• 167273-28-1 1-[4-(3-Chloro-benzyl)-piperazin-1-yl]-3-phenyl-propan-2-one 
• 939756-94-2 2-chloro-1-(4-(3-chlorobenzyl)piperazin-1-yl)ethanone 
• 1289155-10-7 (S)-2-((1-(benzylsulfonyl)pyrrolidin-3-yl)amino)-1-(4-(3-chlorobenzyl)piperazin-1-yl)ethanone 
• 1345846-01-6 C₂₀H₂₁ClF₂N₄O₂ 
• 1345843-65-3 2-(4-(3-chlorobenzyl)piperazin-1-yl)acetohydrazide 
• 1239956-45-6 C₂₄H₂₇ClN₂O₅ 
• 1610735-11-9 (1R,2R)-2-(4-(3-chlorobenzyl)piperazin-1-yl)-1,2-dihydronaphthalen-1-ol 

Relevant academic research and scientific papers

Design, synthesis and SAR of antitubercular benzylpiperazine ureas

Abstract: N-furfuryl piperazine ureas disclosed by scientists at GSK Tres Cantos were chosen as antimycobacterial hits from a phenotypic whole-cell screen. Bioisosteric replacement of the furan ring in the GSK Tres Cantos molecules with a phenyl ring led to molecule (I) with an MIC of 1?μM against Mtb H37Rv, low cellular toxicity (HepG2 IC50 ~ 80?μM), good DMPK properties and specificity for Mtb. With the aim of delineating the SAR associated with (I), fifty-five analogs were synthesized and screened against Mtb. The SAR suggests that the piperazine ring, benzyl urea and piperonyl moieties are essential signatures of this series. Active compounds in this series are metabolically stable, have low cellular toxicity and are valuable leads for optimization. Molecular docking suggests these molecules occupy the Q0 site of QcrB like Q203. Graphic Abstract: Bioisosteric replacement of N-furfuryl piperazine-1-carboxamides yielded molecule (I) a novel lead with satisfactory PD, metabolism, and toxicity profiles.[Figure not available: see fulltext.]

Development of 2-amino-4-phenylthiazole analogues to disrupt myeloid differentiation factor 88 and prevent inflammatory responses in acute lung injury

Myeloid differentiation primary response protein 88 (MyD88), an essential adapter protein used by toll-like receptors (TLR), is a promising target molecule for the treatment of respiratory inflammatory diseases. Previous studies explored the activities of novel 2-amino-4-phenylthiazole analogue (6) in inflammation-induced cancer, and identified the analogue as an inhibitor of MyD88 toll/interleukin-1 receptor (TIR) homology domain dimerization. Here, we describe the synthesis of 47 new analogues by modifying different sites on this lead compound and assessed their anti-inflammatory activities in lipopolysaccharide-induced mouse primary peritoneal macrophages (MPMs). The most promising compound, 15d, was found to effectively interact with MyD88 protein and prevented formation of the MyD88 homodimeric complex. Furthermore, 15d showed in vivo anti-inflammatory activity in LPS-caused model of acute lung injury. This work provides new candidates as MyD88 inhibitors to combat inflammation diseases.

New potent antifungal triazole alcohols containing N-benzylpiperazine carbodithioate moiety: Synthesis, in vitro evaluation and in silico study

A number of 1H-1,2,4-triazole alcohols containing N-(halobenzyl)piperazine carbodithioate moiety have been designed and synthesized as potent antifungal agents. In vitro bioassays against different Candida species including C. albicans, C. glabrata, C. parapsilosis, C. krusei, and C. tropicalis revealed that the N-(4-chlorobenzyl) derivative (6b) with MIC values of 0.063–0.5 μg/mL had the best profile of activity, being 4–32 times more potent than fluconazole. Docking simulation studies confirmed the better fitting of compound 6b in the active site of lanosterol 14α-demethylase (CYP51) enzyme, the main target of azole antifungals. Particularly, the potential of compound 6b against fluconazole-resistant isolates along with its minimal toxicity against human erythrocytes and HepG2 cells make this prototype compound as a good lead for discovery of potent and safe antifungal agents.

Synthesis and bioactive evaluations of novel benzotriazole compounds as potential antimicrobial agents and the interaction with calf thymus DNA

A novel series of benzotriazole derivatives were synthesized and characterized by NMR, IR and MS spectra. The bioactive assay manifested that most of the new compounds exhibited moderate to good antibacterial and antifungal activities against the tested strains in comparison to reference drugs chloromycin, norfloxacin and fluconazole. Especially, 2,4-dichlorophenyl substituted benzotriazole derivative 6f displayed good antibacterial activity against MRSA with MIC value of 4 μg/mL, which was 2-fold more potent than Chloromycin, and it also displayed 3-fold stronger antifungal activity (MIC = 4 μg/mL) than fluconazole (MIC = 16 μg/mL) against Beer yeast. The preliminary interactive investigations of compound 6f with calf thymus DNA revealed that compound 6f could effectively intercalate into DNA to form compound 6f-DNA complex which might block DNA replication to exert antimicrobial activities. Molecular docking experiments suggested that compound 6f projected into base-pairs of DNA hexamer duplex forming two hydrogen bonds with guanine of DNA. The theoretical calculations were in accordance with the experimental results.

A newly synthesized sinapic acid derivative inhibits endothelial activation in vitro and in vivos

Inhibition of oxidative stress and inflammation in vascular endothelial cells (ECs) may represent a new therapeutic strategy against endothelial activation. Sinapic acid (SA), a phenylpropanoid compound, is found in natural herbs and high-bran cereals and has moderate antioxidant activity. We aimed to develop new SA agents with the properties of antioxidation and blocking EC activation for possible therapy of cardiovascular disease. We designed and synthesized 10 SA derivatives according to their chemical structures. Preliminary screening of the compounds involved scavenging hydroxyl radicals and 2,2-diphenyl-1- picrylhydrazyl (DPPH×), croton oil-induced ear edema in mice, and analysis of the mRNA expression of adhesion molecules in ECs. 1- Acetyl-sinapic acyl-4-(39-chlorine-)benzylpiperazine (SA9) had the strongest antioxidant and anti-inflammatory activities both in vitro and in vivo. Thus, the effect of SA9 was further studied. SA9 inhibited tumor necrosis factor a-induced upregulation of adhesion molecules in ECs at both mRNA and protein levels, as well as the consequent monocyte adhesion to ECs. In vivo, result of face-toface immunostaining showed that SA9 reduced lipopolysaccharideinduced expression of intercellular adhesion molecule-1 in mouse aortic intima. To study the molecular mechanism, results from luciferase assay, nuclear translocation of NF-kB, and Western blot indicated that the mechanism of the anti-inflammatory effects of SA9 might be suppression of intracellular generation of ROS and inhibition of NF-kB activation in ECs. SA9 is a prototype of a novel class of antioxidant with anti-inflammatory effects in ECs. It may represent a new therapeutic approach for preventing endothelial activation in cardiovascular disorders.

PROCASPASE-ACTIVATING COMPOUNDS AND COMPOSITIONS

The invention provides compounds and compositions useful for the modulation of certain enzymes. The compounds and compositions can induce of cell death, particularly cancer cell death. The invention also provides methods for the synthesis and use of the compounds and compositions, including the use of compounds and compositions in therapy for the treatment of cancer and selective induction of apoptosis in cells.

Synthesis and receptor binding studies of novel 4,4-disubstituted arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as a new class of σ1 ligands

This study presents the synthesis and biological evaluation of a new series of arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as sigma receptor ligands. It was found that a number of halogen substituted sulfonamides display relatively high and low affinities to σ1 and σ2 receptors, respectively. The σ1 affinities and subtype selectivities of four piperidine derivatives were also found to be generally comparable to those of piperazine analogues. Compared to σ1-Rs compounds with n = 0 and 2, those with n = 1 proved to have optimal length of carbon chain by exhibiting higher affinities. Within this series, the 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine sigma ligand was identified with 96-fold σ1/σ2 selectivity ratio (Kiσ1 = 0.96 ± 0.05 nM and K iσ2 = 91.8 ± 8.1 nM).

Gas-phase nucleophilic aromatic substitution between piperazine and halobenzyl cations: Reactivity of the methylene arenium form of benzyl cations

Methylene arenium involved in SNAr: The gas-phase nucleophilic aromatic substitution reactions of halobenzyl cations with piperazine through a cationic σ complex were studied using ESI mass spectrometry. This study demonstrates that the methylene arenium form of halobenzyl cations exhibits nucleophilic substitution reactivity at the phenyl ring (see scheme). Copyright

Exploration of (S)-3-aminopyrrolidine as a potentially interesting scaffold for discovery of novel Abl and PI3K dual inhibitors

Based on the literature-reported compensatory effect of PI3K on Abl inhibition and the improved preclinical effect of drug combination of Abl and PI3K inhibitors, a series of compounds bearing novel scaffold of (S)-3-aminopyrrolidine was identified as Abl and PI3K dual inhibitors through support vector machine screening tool, which were subsequently synthesized and tested. Most compounds demonstrated promising cytoxicity against a CML leukemia cell-line K562 and moderate inhibition against Abl and PI3K kinases. These compounds induced no apoptosis in K562 cell-line, suggesting that their cytotoxic activities are unlikely duo to other known anti-CML mechanisms. Molecular docking study further showed that the compound 5k could bind with both Abl and PI3K, but the weaker binding with Abl compared to Imatinib is consistent with its low kinase inhibitory rates. These plus literature-reported evidences suggest that the promising cytotoxic effect of our novel compounds might be due to the collective effect of Abl and PI3K inhibition.

Design and Synthesis of Novel Insecticides Based on the Serotonergic Ligand 1-[(4-Aminophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine(PAPP)

1-[(4-Aminophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine (PAPP) is a 5-HT1A agonist and was reported to display high affinity for serotonin (5-HT) receptor from the parasitic nematode Haemonchus contortus. The present investigation explored the possibility of using PAPP as a lead compound of new insecticides with novel mode of action. On the basis of the PAPP scaffold, a series of 1-arylmethyl-4-[(trifluoromethyl)pyridin-2-yl]piperazine derivatives were designed, synthesized, and evaluated for biological activities against the armyworm Pseudaletia separata (Walker). Bioassays showed that most of the target compounds displayed certain growth-inhibiting activities or larvicidal activities against armyworm. The quantitative structure-activity relationship (QSAR) for growth-inhibiting activities was also analyzed and established.