6574-15-8

Usage

Uses

Used in Pharmaceutical Industry:
1-(4-Nitrophenyl)piperidine is used as a key intermediate in the synthesis of various pharmaceuticals for its significant biological activity. It contributes to the development of potential drug candidates, playing a crucial role in medicinal chemistry.
Used in Research Chemicals:
In the field of research, 1-(4-Nitrophenyl)piperidine is used as a building block for the creation of new chemical entities. Its unique structure allows for exploration in various research areas, including the study of its pharmacological properties and potential applications.
Used in Organic Synthesis:
1-(4-Nitrophenyl)piperidine is utilized as a versatile building block in organic synthesis, enabling the production of a wide range of compounds. Its structural properties make it suitable for the synthesis of agrochemicals, dyes, and other specialty chemicals, contributing to the development of new products in these industries.
Used in Development of New Compounds:
Due to its structural and pharmacological properties, 1-(4-Nitrophenyl)piperidine is an important intermediate in the development of new compounds for medical and industrial purposes. Its potential applications in various fields make it a valuable asset in the advancement of chemical research and product development.

InChI:InChI=1/C23H21N5O4S/c1-13-8-10-14(11-9-13)28-20(30)15-6-4-5-7-16(15)25-22(28)33-12-17(29)18-19(24)26(2)23(32)27(3)21(18)31/h4-11H,12,24H2,1-3H3

Upstream product

• 110-89-4 piperidine 
• 98-95-3 nitrobenzene 
• 100-00-5 4-chlorobenzonitrile 
• 350-46-9 4-Fluoronitrobenzene 
• 4096-20-2 N-phenyl piperidine 
• 111-24-0 1,5-dibromo-pentane 
• 100-01-6 4-nitro-aniline 
• 636-98-6 p-nitrobenzene iodide 
• 100-17-4 para-methoxynitrobenzene 
• 626-67-5 N-methylcyclohexylamine 
• 42106-50-3 2-piperidino-5-nitrobenzoic acid 
• 586-78-7 para-nitrophenyl bromide 
• 1501-26-4 methyl 4-(chlorocarbonyl)butyrate 
• 40832-54-0 1-(4-nitrophenyl)piperidine N-oxide 

Downstream Products

• 192323-89-0 4-piperidino-cyclohexylamine 
• 2359-60-6 4-(1-piperidino)aniline 
• 839-93-0 1-(2,4-dinitrophenyl)piperidine 
• 379255-22-8 2-chloro-N-(4-(piperidin-1-yl)phenyl)acetamide 
• 30130-59-7 N-(4-(piperidin-1-yl)phenyl)formamide 

Relevant academic research and scientific papers

Rate and Yield Enhancements in Nucleophilic Aromatic Substitution Reactions via Mechanochemistry

A variety of nucleophilic aromatic substitution reactions were carried out mechanochemically to great advantage. On average, reactions rates were nine-times faster. The corresponding kinetic studies presented provide the clearest head-to-head kinetic comparisons between mechanochemical and conventional systems at identical temperatures. Attempts are provided at classifying the kinetics of one example. Removal of polar, protic solvents from these reactions presents environmental benefits to a reaction class whose kinetics are heavily dependent on such solvents.

Optimization of WZ4003 as NUAK inhibitors against human colorectal cancer

NUAK, the member of AMPK (AMP-activated protein kinase) family of protein kinases, is phosphorylated and activated by the LKB1 (liver kinase B1) tumor suppressor protein kinase. Recent work has indicated that NUAK1 is a key component of the antioxidant stress response pathway, and the inhibition of NUAK1 will suppress the growth and survival of colorectal tumors. As a promising target for anticancer drugs, few inhibitors of NUAK were developed. With this goal in mind, based on NUAK inhibitor WZ4003, a series of derivatives has been synthesized and evaluated for anticancer activity. Compound 9q, a derivative of WZ4003 by removing a methoxy group, was found to be the most potential one with stronger inhibitory against NUAK1/2 enzyme activity, tumor cell proliferation and inducing apoptosis of tumor cells. By in vivo efficacy evaluations of colorectal SW480 xenografts, 9q suppresses tumor growth more effectively with an excellent safety profile in vivo and is therefore seen as a suitable candidate for further investigation.

Nucleophilic aromatic substitution reactions under aqueous, mild conditions using polymeric additive HPMC

The use of the inexpensive, benign, and sustainable polymer, hydroxypropyl methylcellulose (HPMC), in water enables nucleophilic aromatic subsitution (SNAr) reactions between various nucleophiles and electrophiles. The mild reaction conditions facilitate a broad functional group tolerance that can be utilized for subsequent derivatization for the synthesis of pharmaceutically relevant building blocks. The use of only equimolar amounts of all reagents and water as reaction solvent reveals the greenness and sustainability of the methodology presented herein.

Ligand compound for copper catalyzed aryl halide coupling reaction, catalytic system and coupling reaction

The invention provides a ligand compound capable of being used for copper catalyzed aryl halide coupling reaction, the ligand compound is a three-class compound containing a 2-(substituted or non-substituted) aminopyridine nitrogen-oxygen group, and the invention also provides a catalytic system for the aryl halide coupling reaction. Thecatalytic system comprises a copper catalyst, a compound containing a 2-(substituted or non-substituted) aminopyridine nitrogen-oxygen group adopted as a ligand, alkali and a solvent, and meanwhile, the invention also provides a system for the aryl halide coupling reaction adopting the catalyst system. The compound containing the 2-(substituted or non-substituted) aminopyridine nitrogen oxygen group can be used as the ligand for the copper catalyzed aryl chloride coupling reaction, and the ligand is stable under a strong alkaline condition and can well maintain catalytic activity when being used for the copper-catalyzed aryl chloride coupling reaction. In addition, the copper catalyst adopting the compound as the ligand can particularly effectively promote coupling of copper catalyzed aryl chloride and various nucleophilic reagents which are difficult to generate under conventional conditions, C-N, C-O and C-S bonds are generated, and numerous useful small molecule compounds are synthesized. Therefore, the aryl halide coupling reaction has a very good large-scale application prospect by adopting the copper catalysis system of the ligand.

Discovery of benzo[d]oxazole derivatives as the potent type-I FLT3-ITD inhibitors

Fms-like tyrosine kinase 3 (FLT3) has been considered as a potential drug target for the treatment of acute myeloid leukemia (AML), because of its high and aberrant expression in AML patients, especially the patients with FLT3-ITD mutation. Initiating from a hit compound (IC50: 500 nM against FLT3-ITD), a series of compounds were designed and synthesized based on benzo[d]oxazole-2-amine scaffold to discover new potent FLT3-ITD inhibitors. During the medicinal chemistry works, flexible molecular docking was used to provide design rationale and study the binding modes of the target compounds. Through the mixed SAR exploration based on the enzymatic and cellular activities, compound T24 was identified with potent FLT3-ITD inhibitory (IC50: 0.41 nM) and anti-proliferative (IC50: 0.037 μM against MV4-11 cells) activities. And the binding mode of T24 with “DFG-in” FLT3 was simulated by a 20-ns molecular dynamics run, providing some insights into further medicinal chemistry efforts toward novel FLT3 inhibitors in AML therapy.

Synthesis and Structure-Activity Relationships of Arylsulfonamides as AIMP2-DX2 Inhibitors for the Development of a Novel Anticancer Therapy

AIMP2-DX2, a splicing variant of AIMP2, is up-regulated in lung cancer, possesses oncogenic activity, and results in tumorigenesis. Specifically inhibiting the interaction between AIMP2-DX2 and HSP70 to suppress AIMP2-DX2-dependent cancers with small molecules is considered a promising avenue for cancer therapeutics. Optimization of hit BC-DXI-04 (IC50 = 40.1 μM) provided new potent sulfonamide based AIMP2-DX2 inhibitors. Among these, BC-DXI-843 showed improved inhibition against AIMP2-DX2 (IC50 = 0.92 μM) with more than 100-fold selectivity over AIMP2 in a luciferase assay. Several binding assays indicated that this compound effectively induces cancer cell apoptosis by specifically interrupting the interaction between DX2 and HSP70, which leads to the degradation of DX2 via Siah1-mediated ubiquitination. More importantly, BC-DXI-843 demonstrated in vivo efficacy in a tumor xenograft mouse model (H460 cells) at a dosage of 50 mg/kg, suggesting it as a promising lead for development of novel therapeutics targeting AIMP2-DX2 in lung cancer.

Development, synthesis and biological investigation of a novel class of potent PC-PLC inhibitors

Phospholipases are enzymes that are involved in the hydrolysis of acyl and phosphate esters of phospholipids, generating secondary messengers that have implications in various cellular processes including proliferation, differentiation and motility. As such inhibitors of phospholipases have been widely studied for their use as anti-cancer therapeutics. Phosphatidylcholine-specific phospholipase C (PC-PLC) is implicated in the progression of a number of cancer cell lines including aggressing triple-negative breast cancers. Most current studies on PC-PLC have utilised D609 as the standard inhibitor however it is known to have multiple failings, including poor stability in aqueous media. 2-Morpholinobenzoic acids were recently identified using vHTS as a potential class of lead compounds, with improvements over D609. In this work 129 analogues in this class were prepared and their PC-PLC inhibitory activity was assessed. It was found that the majority of these novel compounds had improved activity when compared to D609 with the most potent inhibitors completely inhibiting enzyme activity. It was determined that the best compound/s contained a morpholino and 2-substituted N-benzyl moieties with these findings explained using molecular modelling. The compounds reported here will allow for improved study of PC-PLC activity.

Cp*Co(iii) and Cu(OAc)2bimetallic catalysis for Buchwald-type C-N cross coupling of aryl chlorides and amines under base, inert gas & solvent-free conditions

A strategy involving bimetallic catalysis with a combination of Cp?Co(CO)I2 and Cu(OAc)2 was used for performing Buchwald-type C-N coupling reactions of aryl chlorides with amines. The reactions proceeded at 100 °C to produce excellent yields of many of the desired C-N coupled products, in 4 h, under aerobic reaction conditions. The reactions were shown to run under base-free and solvent-free conditions, enabling this strategy to work efficiently for electron-withdrawing and base-sensitive functionalities. The presented methodology was found to be equally efficient for electron-donating functionalities as well as for primary (1°) and secondary (2°) aromatic and aliphatic amines. Moreover, the products were easily separated through the extractions of the organic aqueous layer, with this process chromatographic separations is not required.

CuI/2-Aminopyridine 1-Oxide Catalyzed Amination of Aryl Chlorides with Aliphatic Amines

A class of 2-aminopyridine 1-oxides are discovered to be effective ligands for the Cu-catalyzed amination of less reactive (hetero)aryl chlorides. A wide range of functionalized (hetero)aryl chlorides reacted with various aliphatic amines to afford the desired products in good to excellent yields under the catalyst of CuI/2-aminopyridine 1-oxides. Furthermore, the catalyst system worked well for the coupling of cyclic secondary amines and N-methyl benzylamine with (hetero)aryl chlorides.

Half-sandwich (η5-Cp?)Rh(iii) complexes of pyrazolated organo-sulfur/selenium/tellurium ligands: Efficient catalysts for base/solvent free C-N coupling of chloroarenes under aerobic conditions

Three new pyrazolated chalcogenoether ligated Rh(iii) half-sandwich complexes (1-3) were synthesised by the thermal reaction of chalcogenoether (S, Se and Te) substituted 1H-pyrazole ligands (L1-L3) and [(η5-C5Me5)RhCl]2 in methanol. The complexes were fully characterised by various spectroscopic techniques, and the molecular structures of complexes 1 and2 were also established through single crystal X-ray crystallographic analysis, which indicates a pseudo-octahedral half-sandwich piano-stool geometry around the rhodium metal. All three complexes were found to be thermally stable and insensitive towards air and moisture. One mol% of Rh(iii) complexes (1-3) along with 10 mol% of Cu(OAc)2 were explored for the Buchwald-Hartwig type C-N coupling reactions of amine and aryl chloride. Good to excellent yields (89-92%) of the coupling products were obtained with seleno- and thio-ether functionalised pyrazolated Rh(iii) complexes (1 and 2), while an average yield (39%) was obtained with the telluro-ether functionalised complex (3). In contrast to the previously reported C-N coupling reactions the present reaction works under solvent- and base-free conditions, and the coupling reaction is accomplished in just 6 h with a high yield of the coupling product. The present methodology was also found to be efficient for a wide variety of functionalised aryl halides, and aliphatic or aromatic amines (1° and 2°). Moreover, the reaction also enables the C-N coupling of electron-withdrawing substrates and base-sensitive functionalities.