54054-85-2

Usage

Uses

Used in Chemical Synthesis:
1-(3-Nitrophenyl)piperazine is used as a precursor or intermediate for the synthesis of various compounds, such as dyes, pesticides, and pharmaceuticals. Its versatile chemical structure allows for the creation of a wide array of products with different applications.
Used in Biochemistry:
1-(3-Nitrophenyl)piperazine is used as a nitroreductase enzyme in biochemistry. The presence of the nitrophenyl group enables it to participate in enzymatic reactions, making it a valuable tool for studying enzyme activity and related biochemical processes.
Used in Environmental Research:
Although 1-(3-Nitrophenyl)piperazine is a pollutant, its non-biodegradability also makes it a subject of interest in environmental research. Studying its behavior in the environment can help in understanding the impact of similar compounds on ecosystems and in developing strategies for pollution control and remediation.

InChI:InChI=1/C10H13N3O2/c14-13(15)10-3-1-2-9(8-10)12-6-4-11-5-7-12/h1-3,8,11H,4-7H2

Upstream product

• 821-48-7 bis-(2-chloroethyl)amine hydrochloride 
• 99-09-2 3-nitro-aniline 
• 110-85-0 piperazine 
• 402-67-5 3-fluoro-1-nitrobenzene 
• 645-00-1 m-iodonitrobenzene 
• 120-43-4 4-ethoxycarbonylpiperazine 
• 144-55-8 sodium hydrogencarbonate 
• 3958-57-4 1-bromomethyl-3-nitrobenzene 
• 585-79-5 m-nitrobromobenzene 
• 206879-94-9 4-(3-nitro-phenyl)-piperazine-1-carboxylic acid tert-butyl ester 

Downstream Products

• 137965-92-5 1-{1-Methyl-5-[4-(3-nitro-phenyl)-piperazin-1-ylmethyl]-1H-pyrrol-2-ylmethyl}-pyrrolidin-2-one 
• 123547-33-1 1-[[1-methyl-5-[[4-(3-nitrophenyl)-1-piperazinyl]-methyl]-1H-pyrrol-2-yl]-methyl]-2-piperidinone 
• 188915-12-0 2-[4-[4-(m-nitrophenyl)piperazin-1-yl]butyl]-1,3-dioxoperhydropyrrolo[1,2-c]imidazole 
• 145969-84-2 5-methoxy-1-{3-[4-(3-nitrophenyl)-1-piperazinyl]propyl}-3,4-dihydrocarbostyril 
• 182954-78-5 5-Chloro-1-{3-[4-(3-nitrophenyl)-1-piperazinyl]propyl}-3,4-dihydrocarbostyril 
• 328410-00-0 1-(3-chloropropyl)-4-(m-nitrophenyl)piperazine 
• 763916-65-0 2-[4-[4-(m-nitrophenyl)piperazin-1-yl]butyl]-1,4-dioxoperhydropyrido[1,2-a]pyrazine 
• 475652-88-1 1-(5-methyl-1-pyrimidin-2-yl-1H-pyrazol-4-yl)-3-[4-(3-nitro-phenyl)-piperazin-1-yl]-propan-1-one 
• 461719-98-2 2-benzyloxycarbonylamino-5-[4-(3-nitro-phenyl)-piperazin-1-yl]-5-oxo-pentanoic acid tert-butyl ester 
• 716377-43-4 2-ethoxycarbonylamino-5-[4-(3-nitro-phenyl)-piperazin-1-yl]-5-oxo-pentanoic acid tert-butyl ester 
• 716377-48-9 2-(3-ethyl-ureido)-5-[4-(3-nitro-phenyl)-piperazin-1-yl]-5-oxo-pentanoic acid tert-butyl ester 
• 716377-44-5 2-isobutoxycarbonylamino-5-[4-(3-nitro-phenyl)-piperazin-1-yl]-5-oxo-pentanoic acid tert-butyl ester 
• 716377-45-6 2-benzenesulfonylamino-5-[4-(3-nitro-phenyl)-piperazin-1-yl]-5-oxo-pentanoic acid tert-butyl ester 
• 716377-47-8 5-[4-(3-nitro-phenyl)-piperazin-1-yl]-5-oxo-2-phenylacetylamino-pentanoic acid tert-butyl ester 

Relevant academic research and scientific papers

MONOACYLGLYCEROL LIPASE INHIBITORS

Provided are compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof: Also provided are compositions comprising compounds of formula (I). The compounds and compositions are also provided for use as medicaments, for example as medicaments useful in the treatment of a condition modulated by monoacylglycerol lipase (MAGL). Also provided are the use of compounds and compositions for the inhibition of monoacylglycerol lipase (MAGL).

Synthesis and structure-activity relationships of new 2-phenoxybenzamides with antiplasmodial activity

The 2-phenoxybenzamide 1 from the Medicines for Malaria Venture Malaria Box Project has shown promising multi-stage activity against different strains of P. falciparum. It was successfully synthesized via a retrosynthetic approach. Subsequently, twenty-one new derivatives were prepared and tested for their in vitro activity against blood stages of the NF54 strain of P. falciparum. Several insights into structure-activity relationships were revealed. The antiplasmodial activity and cytotoxicity of compounds strongly depended on the substitution pattern of the anilino partial structure as well as on the size of substituents. The diaryl ether partial structure had further impacts on the activity. Additionally, several physicochemical and pharmacokinetic parameters were calculated (log P, log D7.4 and ligand efficiency) or determined experimentally (passive permeability and CYP3A4 inhibition). The tert-butyl-4-{4-[2-(4-fluorophenoxy)-3-(trifluoromethyl)benzamido]phenyl}piperazine-1-carboxylate possesses high antiplasmodial activity against P. falciparum NF54 (PfNF54 IC50 = 0.2690 μM) and very low cytotoxicity (L-6 cells IC50 = 124.0 μM) resulting in an excellent selectivity index of 460. Compared to the lead structure 1 the antiplasmodial activity was improved as well as the physicochemical and some pharmacokinetic parameters.

Covalent inhibition of the histamine H3 receptor

Covalent binding of G protein-coupled receptors by small molecules is a useful approach for better understanding of the structure and function of these proteins. We designed, synthesized and characterized a series of 6 potential covalent ligands for the histamine H3 receptor (H3R). Starting from a 2-amino-pyrimidine scaffold, optimization of anchor moiety and warhead followed by fine-tuning of the required reactivity via scaffold hopping resulted in the isothiocyanate H3R ligand 44. It shows high reactivity toward glutathione combined with appropriate stability in water and reacts selectively with the cysteine sidechain in a model nonapeptide equipped with nucleophilic residues. The covalent interaction of 44 with H3R was validated with washout experiments and leads to inverse agonism on H3R. Irreversible binder 44 (VUF15662) may serve as a useful tool compound to stabilize the inactive H3R conformation and to study the consequences of prolonged inhibition of the H3R.

4-Substituted-2-phenylquinazolines as inhibitors of BCRP

We investigated several 2-phenylquinazolines with different substitutions at position 4 for their BCRP inhibition. Compounds with phenyl ring attached via an amine-containing linker at position 4 were found to be potent inhibitors of BCRP. In general compounds with meta substitution of phenyl ring at position 4 were found to have higher inhibitory effect, compound 12 being the most potent and selective towards BCRP.

Discovering Small-Molecule Estrogen Receptor α/Coactivator Binding Inhibitors: High-Throughput Screening, Ligand Development, and Models for Enhanced Potency

Small molecules, namely coactivator binding inhibitors (CBIs), that block estrogen signaling by directly inhibiting the interaction of the estrogen receptor (ER) with coactivator proteins act in a fundamentally different way to traditional antagonists, which displace the endogenous ligand estradiol. To complement our prior efforts at CBI discovery by denovo design, we used high-throughput screening (HTS) to identify CBIs of novel structure and subsequently investigated two HTS hits by analogue synthesis, finding many compounds with low micromolar potencies in cell-based reporter gene assays. We examined structure-activity trends in both series, using induced-fit computational docking to propose binding poses for these molecules in the coactivator binding groove. Analysis of the structure of the ER-steroid receptor coactivator (SRC) complex suggests that all four hydrophobic residues within the SRC nuclear receptor box sequence are important binding elements. Thus, insufficient water displacement upon binding of the smaller CBIs in the expansive complexation site may be limiting the potency of the compounds in these series, which suggests that higher potency CBIs might be found by screening compound libraries enriched with larger molecules.

Discovery of novel, orally available benzimidazoles as melanin concentrating hormone receptor 1 (MCHR1) antagonists

Melanin concentrating hormone (MCH) is an important mediator of energy homeostasis and plays role in several disorders such as obesity, stress, depression and anxiety. The synthesis and biological evaluation of novel benzimidazole derivatives as MCHR1 antagonists are described. The in vivo proof of principle for weight loss with a lead compound from this series is exemplified.

Unique spirocyclopiperazinium salt III: Further investigation of monospirocyclopiperazinium (MSPZ) salts as potential analgesics

Two novel classes of monospirocyclopiperazinium salts were designed, synthesized, and evaluated for their in vivo analgesic activities. Some interesting structure-activity relationships are revealed: (1) Spirocyclopiperazinium moiety is favorable to improve the analgesic activity; (2) The size and conformation of spirocyclopiperazinium moiety significantly affects the analgesic activity; (3) Phenylethyl group of 3d is a crucial pharmacophore. Among the compounds synthesized, 3d exhibited the most potent activity with low toxicity. Further antinociceptive mechanism studies of 3d showed that these compounds will be a new kind of analgesics.

3,4-dihydro-2-naphthamide derivatives as selective dopamine D3 ligands

The invention relates to 3,4-dihydro-2-naphthamide derivatives of formula (I), pharmaceutical compositions containing them and their therapeutic applications as partial agonists or antagonists of the dopamine D3 receptor for the treatment of neuropsychological disorders.

BENZIMIDAZOLE DERIVATIVES AND THEIR USE FOR MODULATING THE GABAA RECEPTOR COMPLEX

This invention relates to novel benzimidazole derivatives, pharmaceutical compositions containing these compounds, and methods of treatment therewith. The compounds of the invention are useful in the treatment of central nervous system diseases and disorders, which are responsive to modulation of the GABAA receptor complex, and in particular for combating anxiety and related diseases.

An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression

We report the discovery of a novel, potent, and selective amidosulfonamide nonazapirone 5-HT1A agonist for the treatment of anxiety and depression, which is now in Phase III clinical trials for generalized anxiety disorder (GAD). The discovery of 20m (PRX-00023), N-{3-[4-(4- cyclohexylmethanesulfonylaminobutyl)-piperazin-1-yl]phenyl}acetamide, and its backup compounds, followed a new paradigm, driving the entire discovery process with in silico methods and seamlessly integrating computational chemistry with medicinal chemistry, which led to a very rapid discovery timeline. The program reached clinical trials within less than 2 years from initiation, spending less than 6 months in lead optimization with only 31 compounds synthesized. In this paper we detail the entire discovery process, which started with modeling the 3D structure of 5-HT1A using the PREDICT methodology, and then performing in silico screening on that structure leading to the discovery of a 1 nM lead compound (8). The lead compound was optimized following a strategy devised based on in silico 3D models and realized through an in silico-driven optimization process, rapidly overcoming selectivity issues (affinity to 5-HT1A vs α1-adrenergic receptor) and potential cardiovascular issues (hERG binding), leading to a clinical compound. Finally we report key in vivo preclinical and Phase I clinical data for 20m tolerability, pharmacokinetics, and pharmacodynamics and show that these favorable results are a direct outcome of the properties that were ascribed to the compound during the rational structure-based discovery process. We believe that this is one of the first examples for a Phase III drug candidate that was discovered and optimized, from start to finish, using in silico model-based methods as the primary tool.