354813-14-2

Usage

Uses

Used in Pharmaceutical Synthesis:
METHYL 4-(4-METHYLPIPERAZIN-1-YL)BENZOATE is used as an intermediate in the synthesis of pharmaceuticals for its ability to contribute to the formation of complex organic compounds that have medicinal properties.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, METHYL 4-(4-METHYLPIPERAZIN-1-YL)BENZOATE is used as a building block for the development of new drugs, leveraging its chemical structure to create molecules with potential therapeutic effects.
Used in Drug Discovery:
METHYL 4-(4-METHYLPIPERAZIN-1-YL)BENZOATE is utilized in drug discovery processes to explore its potential as a precursor to compounds that could treat various diseases or conditions, given its reported biological activities.
Used in Scientific Research:
METHYL 4-(4-METHYLPIPERAZIN-1-YL)BENZOATE is used in scientific research to study its biological activities and understand its role in chemical reactions and interactions, which could lead to the development of new therapeutic agents or a better understanding of biological processes.

InChI:InChI=1/C13H18N2O2/c1-14-7-9-15(10-8-14)12-5-3-11(4-6-12)13(16)17-2/h3-6H,7-10H2,1-2H3

Upstream product

• 109-01-3 1-methyl-piperazine 
• 403-33-8 methyl 4-flurobenzoate 
• 163210-97-7 methyl 4-(piperazin-1-yl)benzoate 
• 74-88-4 methyl iodide 
• 619-42-1 4-methoxycarbonylphenyl bromide 

Downstream Products

• 289044-60-6 4-(4-methylpiperazin-4-ium-1-yl)benzoic acid chloride 
• 1035270-63-3 N-[5-[2-[3-(methylcarbamoyl)phenyl]ethyl]-2H-pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide 
• 1035269-61-4 N-[5-[2-[5-(dimethylaminomethyl)-2-furyl]ethyl]-1H-pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide 
• 354813-15-3 4-(4-methylpiperazin-1-yI)benzoic acid 
• 909253-26-5 4-(4-methylpiperazin-1-yl)benzamide 

Relevant academic research and scientific papers

Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer

Proteolysis targeting chimera (PROTAC) small-molecule degraders have emerged as a promising new type of therapeutic agents, but the design of PROTAC degraders with excellent oral pharmacokinetics is a major challenge. In this study, we present our strategies toward the discovery of highly potent PROTAC degraders of androgen receptor (AR) with excellent oral pharmacokinetics. Employing thalidomide to recruit cereblon/cullin 4A E3 ligase and through the rigidification of the linker, we discovered highly potent AR degraders with good oral pharmacokinetic properties in mice with ARD-2128 being the best compound. ARD-2128 achieves 67% oral bioavailability in mice, effectively reduces AR protein and suppresses AR-regulated genes in tumor tissues with oral administration, leading to the effective inhibition of tumor growth in mice without signs of toxicity. This study supports the development of an orally active PROTAC AR degrader for the treatment of prostate cancer and provides insights and guidance into the design of orally active PROTAC degraders.

Discovery of a Potent FLT3 Inhibitor (LT-850-166) with the Capacity of Overcoming a Variety of FLT3 Mutations

Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitor resistance that presents a significant clinical challenge. Herein, a series of pyrazole-3-amine derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. The structure-activity relationship and molecular dynamics simulation studies illustrated that the ribose region of FLT3 could be occupied to help address the obstacle of secondary mutations. Among those derivatives, compound 67 exhibited potent and selective inhibitory activities against FLT3-ITD-positive acute myeloid leukemia (AML) cells and possessed equivalent potency against transformed BaF3 cells with a variety of secondary mutations. Besides, cellular mechanism assays demonstrated that 67 strongly inhibited phosphorylation of FLT3 and its downstream signaling factors, as well as induced cell cycle arrest and apoptosis in MV4-11 cells. In the MV4-11 xenograft models, 67 exhibited potent antitumor potency without obvious toxicity. Taken together, these results demonstrated that 67 might be a drug candidate for the treatment of FLT3-ITD-positive AML.

Design, synthesis and biological evaluation of novel 1H-1,2,4-triazole, benzothiazole and indazole-based derivatives as potent FGFR1 inhibitors viafragment-based virtual screening

Fibroblast growth-factor receptor (FGFR) is a potential target for cancer therapy. We designed three novel series of FGFR1 inhibitors bearing indazole, benzothiazole, and 1H-1,2,4-triazole scaffold via fragment-based virtual screening. All the newly synthesised compounds were evaluated in vitro for their inhibitory activities against FGFR1. Compound 9d bearing an indazole scaffold was first identified as a hit compound, with excellent kinase inhibitory activity (IC50 = 15.0 nM) and modest anti-proliferative activity (IC50 = 785.8 nM). Through two rounds of optimisation, the indazole derivative 9 u stood out as the most potent FGFR1 inhibitors with the best enzyme inhibitory activity (IC50 = 3.3 nM) and cellular activity (IC50 = 468.2 nM). Moreover, 9 u also exhibited good kinase selectivity. In addition, molecular docking study was performed to investigate the binding mode between target compounds and FGFR1.

Combining structure- and property-based optimization to identify selective FLT3-ITD inhibitors with good antitumor efficacy in AML cell inoculated mouse xenograft model

FLT3 mutation is among the most common genetic mutations in acute myeloid leukemia (AML), which is also related with poor overall survival and refractory in AML patients. Recently, FLT3 inhibitors have been approved for AML therapy. Herein, a series of new compounds with pyrazole amine scaffold was discovered, which showed potent inhibitory activity against FLT3-ITD and significant selectivity against both FLT3-ITD and AML cells expressing FLT3-ITD. Compound 46, possessing the most promising cellular activity, blocked the autophosphorylation of FLT3 pathway in MV4-11 cell line. Furthermore, the apoptosis and downregulation of P-STAT5 were also observed in tumor cells extracted from the MV4-11 cell xenografts model upon compound 46 treatment. Compound 46 was also metabolically stable in vitro and suppressed tumor growth significantly in MV4-11 xenografts model in vivo. Compound 46 showed no toxicity to the viscera of mice and caused no decrease in body weight of mice. In conclusion, the results of this study could provide valuable insights into discovery of new FLT3 inhibitors, and compound 46 was worthy of further development as potential drug candidate to treat AML.

C-3 NOVEL TRITERPENONE WITH C-17 REVERSE AMIDE DERIVATIVES AS HIV INHIBITORS

The present invention relates to C-3 novel triterpenone with C-17 reverse amide compounds of Formula (I); and pharmaceutically acceptable salts thereof, wherein ring Formula (II), R1, R2, R3, R4, R5, R6, R7, 'n' and 'm' are as defined in Formula (I). The invention also relates to C-3 novel triterpenone with C-17 reverse amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.

Optimization of 1H-indazol-3-amine derivatives as potent fibroblast growth factor receptor inhibitors

Fibroblast growth factor receptor (FGFR) is a potential target for cancer therapy because of its critical role in promoting cancer formation and progression. In a continuing effort to improve the cellular activity of hit compound 7r bearing an indazole scaffold, which was previously discovered by our group, several compounds harnessing fluorine substituents were designed, synthesized and biological evaluated. Besides, the region extended out to the ATP binding pocket toward solvent was also explored. Among them, compound 2a containing 2,6-difluoro-3-methoxyphenyl residue exhibited the most potent activities (FGFR1: less than 4.1?nM, FGFR2: 2.0?±?0.8?nM). More importantly, compound 2a showed an improved antiproliferative effect against KG1 cell lines and SNU16 cell lines with IC50 values of 25.3?±?4.6?nM and 77.4?±?6.2?nM respectively.

One kind of substituted aminopyridine compound and preparation and application thereof

The invention provides one kind of substituted aminopyridine compound and a preparation and application thereof. Specifically, the invention provides a compound shown as the formula (I), and groups of the formula (I) are shown as in the description. The c

Dipeptide nitrile cathepsin K inhibitors

Dipeptide nitrile Cathepsin K inhibitors of formula I, and pharmaceutically acceptable salts or esters thereof In which R1 and R2 are independently H or C1-C7lower alkyl, or R1 and R2 toget