16155-03-6

Usage

Uses

Used in Pharmaceutical Industry:
1-Methyl-4-(4-nitrophenyl)piperazine is used as a reagent for the preparation of diaminopyrimidines, which serve as reversible and irreversible inhibitors of mutant EGFR (epidermal growth factor receptor) tyrosine kinases. These inhibitors are crucial in the treatment of non-small-cell lung cancer, as they help regulate the abnormal cell growth associated with the disease.
Additionally, 1-Methyl-4-(4-nitrophenyl)piperazine is utilized in the preparation of disubstituted pyrimidine compounds. These compounds act as inhibitors for EGFR and/or ALK (anaplastic lymphoma kinase), which are relevant in the treatment of various diseases. By targeting these specific proteins, the compound can potentially improve therapeutic outcomes and provide more effective treatment options for patients.

InChI:InChI=1/C11H15N3O2/c1-12-6-8-13(9-7-12)10-2-4-11(5-3-10)14(15)16/h2-5H,6-9H2,1H3/p+1

Upstream product

• 109-01-3 1-methyl-piperazine 
• 100-00-5 4-chlorobenzonitrile 
• 350-46-9 4-Fluoronitrobenzene 
• 7440-44-0 pyrographite 
• 321898-63-9 4-(4-nitrophenyl)piperazine-1-carbaldehyde 
• 6269-89-2 1-(4-Nitrophenyl)piperazine 
• 463-57-0 methanediol 
• 50-00-0 formaldehyd 
• 260252-87-7 4-(4'-nitrophenyl)piperazine hydrochloride 
• 636-98-6 p-nitrobenzene iodide 
• 74-88-4 methyl iodide 
• 586-78-7 para-nitrophenyl bromide 

Downstream Products

• 16153-81-4 4-(4-Methyl-piperazino)-anilin 
• 106365-89-3 4-(4-methylpiperazin-1-yl)benzenethiol 
• 106365-99-5 2-(4-(4-methylpiperazino)phenylthio)benzoic acid 
• 106365-93-9 4'-(4-Methylpiperazino)phenyl 2,4-Dinitrophenyl Sulfide 
• 760975-51-7 1,1-dimethyl-4-(4-nitrophenyl)piperazin-1-ium methyl sulphate 
• 1199795-12-4 1-methyl-4-{4-nitro-3-[(1-naphthalenesulfonyl)methyl]phenyl}piperazine 
• 1253422-19-3 C₁₈H₂₀ClN₃O₄S 
• 1253422-24-0 C₁₉H₂₃N₃O₄S 
• 1253422-26-2 C₁₆H₁₉N₃O₄S₂ 
• 1253422-27-3 C₁₈H₁₉Cl₂N₃O₄S 
• 1253422-23-9 C₁₉H₂₃N₃O₅S 
• 1253422-15-9 C₁₈H₂₁N₃O₄S 
• 1253422-25-1 C₁₉H₂₃N₃O₄S 
• 1253422-21-7 C₁₈H₂₀ClN₃O₄S 

Relevant academic research and scientific papers

Safety-catch linker strategies for the production of radiopharmaceuticals labeled with positron-emitting isotopes

A novel synthetic stratetegy for compounds labeled with the positron-emitting isotope carbon-11 is described. The use of precursors attached to a solid support via safety-catch linkers allows selective release of radiolabeled material, leaving unreacted precursor attached to the support. Two different linkers demonstrate the application to the preparation of radiolabeled N-alkyl tertiary amines and N-alkylsulfonamides. This technique is expected to lead to more widespread use of positron emission tomography for the in vivo analysis of compound behavior. Copyright

Discovery and in Vivo Anti-inflammatory Activity Evaluation of a Novel Non-peptidyl Non-covalent Cathepsin C Inhibitor

Cathepsin C (Cat C) participates in inflammation and immune regulation by affecting the activation of neutrophil serine proteases (NSPs). Therefore, cathepsin C is an attractive target for treatment of NSP-related inflammatory diseases. Here, the complete discovery process of the first potent "non-peptidyl non-covalent cathepsin C inhibitor"was described with hit finding, structure optimization, and lead discovery. Starting with hit 14, structure-based optimization and structure-activity relationship study were comprehensively carried out, and lead compound 54 was discovered as a potent drug-like cathepsin C inhibitor both in vivo and in vitro. Also, compound 54 (with cathepsin C Enz IC50 = 57.4 nM) exhibited effective anti-inflammatory activity in an animal model of chronic obstructive pulmonary disease. These results confirmed that the non-peptidyl and non-covalent derivative could be used as an effective cathepsin C inhibitor and encouraged us to continue further drug discovery on the basis of this finding.

COMPOUNDS AND THEIR USES AS SPLEEN TYROSINE KINASE INHIBITORS

Provided are compounds of Formula (I) which can be used as Syk inhibitors and potently as therapeutic agents against diseases mediated by Syk.

NOTCH INHIBITORS AND USES THEREOF

Disclosed herein, inter alia, are compounds for inhibiting Notch and uses thereof.

Evidence of Rate Limiting Proton Transfer in an SNAr Aminolysis in Acetonitrile under Synthetically Relevant Conditions

An early synthetic step in the synthesis of adavosertib, AZD1775, is the SNAr reaction between 4-fluoronitrobenzene and 1-methylpiperazine in acetonitrile. A simple kinetics-based design of four reaction profiling experiments was used to invest

FUSED PYRIMIDINE COMPOUNDS, COMPOSITIONS AND MEDICINAL APPLICATIONS THEREOF

The present disclosure relates to a class of fused pyrimidine compounds of Formula I, their stereoisomers, tautomers, pharmaceutically acceptable salts, polymorphs, solvates, and hydrates thereof. The present disclosure also relates to a process of preparation of these fused pyrimidine compounds, and to pharmaceutical compositions containing them.

NOVEL SULFONAMIDE DERIVATIVE WITH FUSED PYRIMIDINE SKELETON, HAVING EPIDERMAL GROWTH FACTOR RECEPTOR MUTATION INHIBITORY EFFECT

The present invention relates to a novel fused pyrimidine based sulfonamide derivative represented by Formula I, a solvate thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition including the same as an active ingredient. The novel fused pyrimidine based sulfonamide derivative of the present invention can effectively suppress the growth of cancer cells and resistance to drugs, which are induced by mutations in the tyrosine kinase domain of epidermal growth factor receptors, or the growth of cancer cells having such resistance.

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.

Discovery of a Pyrimidothiazolodiazepinone as a Potent and Selective Focal Adhesion Kinase (FAK) Inhibitor

Focal adhesion kinase (FAK) is a tyrosine kinase with prominent roles in protein scaffolding, migration, angiogenesis, and anchorage-independent cell survival and is an attractive target for the development of cancer therapeutics. However, current FAK inhibitors display dual kinase inhibition and/or significant activity on several kinases. Although multitargeted activity is at times therapeutically advantageous, such behavior can also lead to toxicity and confound chemical-biology studies. We report a novel series of small molecules based on a tricyclic pyrimidothiazolodiazepinone core that displays both high potency and selectivity for FAK. Structure-activity relationship (SAR) studies explored modifications to the thiazole, diazepinone, and aniline "tail,"which identified lead compound BJG-03-025. BJG-03-025 displays potent biochemical FAK inhibition (IC50 = 20 nM), excellent kinome selectivity, activity in 3D-culture breast and gastric cancer models, and favorable pharmacokinetic properties in mice. BJG-03-025 is a valuable chemical probe for evaluation of FAK-dependent biology.

The synthesis and bioactivity of pyrrolo[2,3-d]pyrimidine derivatives as tyrosine kinase inhibitors for NSCLC cells with EGFR mutations

EGFR mutations are an ongoing challenge in the treatment of NSCLC, and demand continuous updating of EGFR TKI drug candidates. Pyrrolopyrimidines are one group of versatile scaffolds suitable for tailored drug development. However not many precedents of this type of pharmacophore have been investigated in the realm of third generation of covalent EGFR-TKIs. Herein, a series of pyrrolo[2,3-d]pyrimidine derivatives able to block mutant EGFR activity in a covalent manner were synthesized, through optimized Buchwald-Hartwig C–N cross coupling reactions. Their preliminary bioactivity and corresponding inhibitory mechanistic pathways were investigated at molecular and cellular levels. Several compounds exhibited increased biological activity and enhanced selectivity compared to the control compound. Notably, compound 12i selectively inhibits HCC827 cells harboring the EGFR activating mutation with up to 493-fold increased efficacy compared to in normal HBE cells. Augmented selectivity was also confirmed by kinase enzymatic assay, with the test compound selectively inhibiting the T790 M activating mutant EGFRs (IC50 values of 0.21 nM) with up to 104-fold potency compared to the wild-type EGFR (IC50 values of 22 nM). Theoretical simulations provide structural evidence of selective kinase inhibitory activity. Thus, this series of pyrrolo[2,3-d]pyrimidine derivatives could serve as a starting point for the development of new EGFR-TKIs.