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 
• 636-98-6 p-nitrobenzene iodide 
• 100-17-4 para-methoxynitrobenzene 
• 17763-80-3 para-nitrophenyl triflate 
• 14150-94-8 3,5-dinitro-1-methyl-2-pyridone 
• 67-64-1 acetone 
• 1153-45-3 4-nitrophenyl 4-methylbenzenesulfonate 
• 23493-34-7 1-methyl-3-nitropyridinium iodide 
• 112882-12-9 2,2,2-Trifluoro-1,1-diphenyl-ethanesulfonic acid 4-nitro-phenyl ester 
• 72078-79-6 1-(2-pyridyl)-3,5-dinitro-2-pyridone 
• 120952-12-7 2-(4-nitrophenoxy)-N-ethylpyridinium tetraphenylborate 

Downstream Products

• 1393367-48-0 1-(4-azidophenyl)piperidine 
• 1393367-61-7 1-(4-(4-((4-chlorophenox)ymethyl)-1H-1,2,3-triazol-1-yl)phenyl)piperidine 
• 1393367-62-8 1-(4-(4-(p-tolyloxymethyl)-1H-1,2,3-triazol-1-yl)-phenyl)piperidine 
• 693235-85-7 N-(2''-methoxybenzyl)-4-(piperidin-1'-yl)aniline 
• 30130-59-7 N-(4-(piperidin-1-yl)phenyl)formamide 
• 2632-65-7 4-pyrrolidin-1-yl-aniline 

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.

Phenazine-Based Donor Acceptor Systems as Organic Photocatalysts for "metal-free" C-N/C-C Cross-Coupling

With an aim to achieve a balance between ground-state and excited-state reduction potential of donor acceptor systems for efficient C-N/C-C cross-coupling, a series of donor acceptor systems DA1-DA4 have been synthesized by varying the donor strength and connecting positions. With an increase in donor strength, systematic elevation in the ground-state reduction potential and decrease in the HOMO-LUMO gap was observed. Interestingly, all the derivatives DA1-DA4 could catalyze the C-N bond formation reaction between activated aryl halides and amines at low catalytic loading under metal-free conditions without the need of any external base upon irradiation with white LED. A balance was realized in the case of derivative DA2, which exhibits high efficiency in C-N couplings. Different control experiments support the validity of the energy as well as electron transfer pathways in the visible light-mediated C-N bond formation. This study further reveals the potential of derivative DA1 in "metal-free"Sonogashira coupling involving activated aryl halides which is attributed to its high excited-state reduction potential.

Integrating CuO?Fe2O3 Nanocomposites and Supramolecular Assemblies of Phenazine for Visible-Light Photoredox Catalysis

A photoredox catalytic ensemble consisting of CuO-Fe2O3 nanocomposites and oligomeric derivative of phenazine has been developed. The prepared system acts as an efficient photoredox catalyst for C?N bond formation reaction via SET mechanism under ‘green’ conditions (aerial environment, mixed aqueous media, recyclable), requiring less equivalents of base and amine substrate. The present study demonstrates the significant role of supramolecular assemblies as photooxidants and reductants upon irradiation and their important contribution towards the activation of the metallic centre through energy transfer and electron transfer pathways. The potential of oligomer 4: CuO-Fe2O3 has also been explored for C?C bond formation reactions via the Sonogashira protocol.

Discovery and SARs of 5-Chloro- N4-phenyl- N2-(pyridin-2-yl)pyrimidine-2,4-diamine Derivatives as Oral Available and Dual CDK 6 and 9 Inhibitors with Potent Antitumor Activity

Cyclin-dependent kinases (CDKs) are promising therapeutic targets for cancer therapy. Herein, we describe our efforts toward the discovery of a series of 5-chloro-N4-phenyl-N2-(pyridin-2-yl)pyrimidine-2,4-diamine derivatives as dual CDK6 and 9 inhibitors. Intensive structural modifications lead to the identification of compound 66 as the most active dual CDK6/9 inhibitor with balancing potency against these two targets and good selectivity over CDK2. Further biological studies revealed that compound 66 was directly bound to CDK6/9, resulting in suppression of their downstream signaling pathway and inhibition of cell proliferation by blocking cell cycle progression and inducing cellular apoptosis. More importantly, compound 66 significantly inhibited tumor growth in a xenograft mouse model with no obvious toxicity, indicating the promising therapeutic potential of CDK6/9 dual inhibitors for cancer treatment. Therefore, the above results are of great importance in the development of dual CDK6/9 inhibitors for cancer therapy.

Design, synthesis and biological evaluation of novel osthole-based derivatives as potential neuroprotective agents

A total of 26 compounds based on osthole skeleton were designed, synthesized. Their cytoprotective abilities of antioxidation, anti-inflammation and Aβ42(Amyloid β-protein 42)-induced neurotoxicity were evaluated by MTT assays. Mechanism of the action of selected compounds were investigated by molecular docking. AlogP, logS and blood–brain barrier (BBB) permeability of all these compounds were simulated by admetSAR. Most of the compounds showed better antioxidative and anti-inflammatory activities compared with osthole, especially OST7 and OST17. The compound OST7 showed relative high activity in neuroprotection against H2O2 (45.7 ± 5.5%), oxygen glucose deprivation (64.6 ± 4.8%) and Aβ42 (61.4 ± 5.2%) at a low concentration of 10 μM. EC50 of selected compounds were measured in both H2O2 and OGD induced cytotoxicity models. Moreover, NO inhibiting ability of OST17(50.4 ± 7.1%) already surpassed the positive drug indomethacin. The structure activity relationship study indicated that introduction of piperazine group, tetrahydropyrrole group and aromatic amine group might be beneficial for enhancement of osthole neuroprotective properties. Molecular docking explained that the reason OST7 exhibited relatively stronger neuroprotection against Aβ because of the greater area of interactions between molecule and target protein. OST7 and OST17 both provided novel methods to investigate osthole as anti-AD drugs.

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.