122833-04-9

Basic information

• Product Name: 1-(4-AMINO-3-METHOXYPHENYL)-4-METHYLPIPERAZINE
• Synonyms: 2-Methoxy-4-(4-methyl-piperazin-1-yl)-phenylamine;2-Methoxy-4-(4-methylpiperazin-1-yl);1-(4-AMINO-3-METHOXYPHENYL)-4-METHYLPIPERAZINE;2-Methoxy-4-(4-methylpiperazin-1-yl)aniline;2-Methoxy-4-(4-methyl-1-piperazinyl)benzenamine;2-Methoxy-4-(4-methylpiperazin-1-yl)benzenamine;BenzenaMine, 2-Methoxy-4-(4-Methyl-1-piperazinyl)-;2-Methoxy-4-(4-methyl-1-piperazinyl)aniline
• CAS NO: 122833-04-9
• Molecular Formula: C₁₂H₁₉N₃O
• Molecular Weight: 221.302
• EINECS: 1533716-785-6
• Mol File: 122833-04-9.mol

Chemical Properties

• Boiling Point: 392℃
• Flash Point: 191℃
• Appearance: /
• Density: 1.111
• Vapor Pressure: 0.0±0.9 mmHg at 25°C
• Refractive Index: 1.574
• Storage Temp.: 2-8°C(protect from light)
• PKA: 7.78±0.42(Predicted)
• CAS DataBase Reference: 1-(4-AMINO-3-METHOXYPHENYL)-4-METHYLPIPERAZINE(CAS DataBase Reference)
• NIST Chemistry Reference: 1-(4-AMINO-3-METHOXYPHENYL)-4-METHYLPIPERAZINE(122833-04-9)
• EPA Substance Registry System: 1-(4-AMINO-3-METHOXYPHENYL)-4-METHYLPIPERAZINE(122833-04-9)

Safety Data

• Hazardous Substances Data: 122833-04-9(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
1-(4-AMINO-3-METHOXYPHENYL)-4-METHYLPIPERAZINE is used as a synthetic intermediate for the development of various pharmaceutical compounds. Its unique structure allows it to be incorporated into the synthesis of a range of therapeutic agents, making it a versatile and valuable component in drug development.
Used in Polo-like Kinase 1 Inhibitors:
1-(4-AMINO-3-METHOXYPHENYL)-4-METHYLPIPERAZINE is used as a key component in the synthesis of 4,5-dihydro-1H-pyrazolo[4,3-h]quinazolines. These compounds are orally and selective Polo-like kinase 1 (PLK1) inhibitors, which play a crucial role in the regulation of cell division and have potential applications in the treatment of various cancers.
Used in IRAK-4 Inhibitors:
In addition to its role in the synthesis of PLK1 inhibitors, 1-(4-AMINO-3-METHOXYPHENYL)-4-METHYLPIPERAZINE is also used in the development of IRAK-4 inhibitors. These compounds target the Interleukin-1 receptor-associated kinase 4 (IRAK-4) enzyme, which is involved in the regulation of inflammatory responses. Inhibiting IRAK-4 has potential therapeutic applications in the treatment of various inflammatory and autoimmune diseases.

InChI:InChI=1S/C12H19N3O/c1-14-5-7-15(8-6-14)10-3-4-11(13)12(9-10)16-2/h3-4,9H,5-8,13H2,1-2H3

Upstream product

• 109-01-3 1-methyl-piperazine 
• 59557-91-4 4-bromo-2-methoxyaniline 
• 6627-53-8 1-chloro-3-methoxy-4-nitrobenzene 
• 761440-26-0 2-methoxy-4-(4-methyl piperazin-1-yl)nitrobenzene 
• 448-19-1 4-fluoro-2-methoxy-1-nitrobenzene 
• 446-36-6 5-fluoro-2-nitrophenol 

Downstream Products

• 1391001-23-2 6-chloro-8-(2-methoxy-4-(4-methylpiperazin-1-yl)phenylamino)-2,7-naphthyridin-1(2H)-one 
• 1390656-45-7 5-(2-methoxy-4-(4-methylpiperazin-1-yl)phenylamino)-7-chloropyrido[4,3-d]pyrimidin-4(3H)-one 
• 1391001-18-5 ethyl 6-(2,6-dichlorobenzyl)-4-(2-methoxy-4-(4-methylpiperazin-1-yl)phenylamino)-2-methylnicotinate 
• 1313036-60-0 ethyl 5-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-1,3,4-thiadiazole-2-carboxylate 
• 1254783-78-2 N-(3-((6-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)oxy)phenyl)acrylamide 
• 1313036-28-0 N-(3-((2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrazolo[1,5-a][1,3,5]triazin-4-yl)oxy)phenyl)acrylamide 
• 1313036-46-2 7-(3-aminophenyl)-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)thieno[3,2-d]pyrimidin-2-amine 
• 1313036-25-7 N-(3-(2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)thieno[3,2-d]pyrimidin-7-yl)phenyl)acrylamide 
• 1313036-49-5 4-(3-aminophenoxy)-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)quinazolin-2-amine 
• 1313036-18-8 N-(3-((2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)quinazolin-4-yl)oxy)phenyl)acrylamide 
• 1313036-53-1 4-(3-aminophenoxy)-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-amine 
• 1313036-54-2 N-(3-((6-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)oxy)phenyl)acrylamide 
• 1313036-58-6 4-(3-aminophenoxy)-N-(2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-2-amine 
• 1313036-44-0 N-(3-((2-((2-methoxy-4-(4-methylpiperazin-1-yl)phenyl)amino)pyrrolo[2,1-f][1,2,4]triazin-4-yl)oxy)phenyl)acrylamide 

Relevant articles and documents

Pyrimidine containing epidermal growth factor receptor kinase inhibitors: Synthesis and biological evaluation

Structure-based design and synthesis of pyrimidine containing reversible epidermal growth factor receptor (EGFR) inhibitors 1a–d are reported. The compounds (1a–d) inhibited the EGFR kinase activity in vitro with IC50 range 740?nm to 3?μm. mRNA

Development of the First Covalent Monopolar Spindle Kinase 1 (MPS1/TTK) Inhibitor

Monopolar spindle kinase 1 (MPS1/TTK) is a key element of the mitotic checkpoint and clinically evaluated as a target in the treatment of aggressive tumors such as triple-negative breast cancer. While long drug-target residence times have been suggested to be beneficial in the context of therapeutic MPS1 inhibition, no irreversible inhibitors have been reported. Here we present the design and characterization of the first irreversible covalent MPS1 inhibitor, RMS-07, targeting a poorly conserved cysteine in the kinase's hinge region. RMS-07 shows potent MPS1 inhibitory activity and selectivity against all protein kinases with an equivalent cysteine but also in a broader kinase panel. We demonstrate potent cellular target engagement and pronounced activity against various cancer cell lines. The covalent binding mode was validated by mass spectrometry and an X-ray crystal structure. This proof of MPS1 covalent ligandability may open new avenues for the design of MPS1-specific chemical probes or drugs.

Synthesis and evaluation of novel 2,4-diaminopyrimidines bearing a sulfoxide moiety as anaplastic lymphoma kinase (ALK) inhibition agents

Anaplastic lymphoma kinase (ALK) targeted therapies have demonstrated remarkable efficacy in ALK-positive lung adenocarcinomas. Here we synthesized and evaluated sixteen new 2,4-diaminopyrimidines bearing a sulfoxide moiety as anaplastic lymphoma kinase (ALK) inhibitors. The optimal compound 9e exhibited excellent antiproliferative activity against non-small cell lung cancer NCI-H2228 cells, which is better than that of Brigatinib and similar to Ceritinib. Mechanism study revealed that the optimal compound 9e decreased the mitochondrial membrane potential and arrested NCI-H2228 cells in the G0/G1 phase, finally resulting in cellular apoptosis. It is interesting that 9e could effectively inhibit the migration of NCI-H2228 cells and may be a promising leading compound for chemotherapy of metastatic cancer.

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.

TYROSINE KINASE NON-RECEPTOR 1 (TNK1) INHIBITORS AND USES THEREOF

Provided herein is a compound of Formula I: or a pharmaceutically acceptable salt thereof, wherein values for the variables (e.g, X11, X22, R11, R22, R33, R44, R55, R66, R77, R88, m, n) are as described herein. Compounds of Formula I, pharmaceutically acceptable salts thereof, pharmaceutical compositions of either of the foregoing, and combinations of any of the foregoing can be used to treat tyrosine kinase non- receptor 1 (TNK1)-mediated diseases, disorders and conditions.

Discovery and structure ? activity relationship exploration of pyrazolo[1,5-a]pyrimidine derivatives as potent FLT3-ITD inhibitors

Internal tandem duplications of FLT3 (FLT3-ITD) occur in approximately 25% of all acute myeloid leukemia (AML) cases and confer a poor prognosis. Optimization of the screening hit 1 from our in-house compound library led to the discovery of a series of pyrazolo[1,5-a]pyrimidine derivatives as potent and selective FLT3-ITD inhibitors. Compounds 17 and 19 displayed potent FLT3-ITD activities both with IC50 values of 0.4 nM and excellent antiproliferative activities against AML cell lines. Especially, compounds 17 and 19 inhibited the quizartinib resistance- conferring mutations, FLT3D835Y, both with IC50 values of 0.3 nM. Moreover, western blot analysis indicated that compounds 17 and 19 potently inhibited the phosphorylation of FLT3 and attenuated downstream signaling in AML cells. These results indicated that pyrazolo[1,5-a]pyrimidine derivatives could be promising FLT3-ITD inhibitors for the treatment AML.

Design, synthesis and biological evaluation of novel pteridinone derivatives as potent dual inhibitors of PLK1 and BRD4

To develop novel simultaneous inhibition of PLK1 and BRD4 bromodomain by a single molecule, three series of novel pteridinone derivatives were designed, synthesized and evaluated for their biological activity. Most compounds exhibited moderate to excellent cytotoxic activity against A549, HCT116, PC-3 and MCF-7 cell lines. The most promising compound III4 showed high antiproliferative effects on four cell lines with IC50 values of 1.27 μM, 1.36 μM, 3.85 μM and 4.06 μM, respectively. The enzymatic assay identified III4 as a potent PLK1 and BRD4 dual inhibitor with % inhibition values of 96.6 and 59.1, respectively. Furthermore, to clarify the anticancer mechanism of the target compounds, explorations in the bioactivity were conducted. The results showed that compound III4 obviously inhibited the proliferation of HCT-116 cell lines, induced a great decrease in the mitochondrial membrane potential leading to apoptosis of cancer cells, suppressed the migration of tumor cells, and arrested the S phase of HCT116 cells.

Design, synthesis and biological evaluation of 2-arylaminopyrimidine derivatives bearing 1,3,8-triazaspiro[4,5]decan-4-one or piperidine-3-carboxamide moiety as novel Type-I1/2 ALK inhibitors

Aiming to develop novel Type-I1/2 inhibitors of ALK to overcome extensive resistance mutations, especially the L1196M mutation surrounding the ATP pocket, two series of 2-arylaminopyrimidine derivatives (11a-f and 22a-t) were designed based on scaffold hopping. The extensive structural elaboration discovered compound 22o which possessed excellent IC50 values of 0.06 and 0.23 μM against ALK-positive Karpas299 and H2228 cell lines, respectively. Meanwhile, 22o displayed encouraging inhibitory potency in the ALKWT (2.5 nM) and ALKL1196M (6.5 nM) enzymatic assays. Furthermore, the AO/EB and Hoechst 33258 assays illustrated 22o could induce cell apoptosis in a dose-dependent manner. Eventually, the molecular docking of 22o with ALK clearly presented the vital interactions within the active site, which was in accordance with Type-I1/2 inhibitor binding mode.

PHENYLAMINOPYRIMIDINE AMIDE AUTOPHAGY INHIBITORS AND METHODS OF USE THEREOF

Described herein are compounds that are inhibitors of autophagy and their use in the treatment of disorders such as cancers.

Aminopyrimidine compound and application thereof in anti-cancer drugs

The invention provides an aminopyrimidine compound and application thereof in anti-cancer drugs. The compound is of the structure shown in the general formula (I), wherein m is 0-4, and n is 0-4; R1 is selected from amino, an alkyl amino group, an amino alkyl group and an alkyl amino carbonyl group; R2 is selected from hydrogen, hydroxyl, nitro, halogen, amino, a cyano group, an alkyl group, an alkenyl group, a halogen alkyl group, a hetero alkyl group, an alkyl amino group, an amino alkyl group, an alkyl carbonyl group, an alkyl amino carbonyl group and a aryl carbonyl group; X is selected from an oxygen atom, an amino group or a methylamino group. The compound can be used for improving the inhibition rate of EGFRT790M and has higher anticancer activity.