Category: piperazines

TCS response regulator OmpR plays a major role in stress resistance, antibiotic resistance, motility, and virulence in Edwardsiella piscicida was written by Huo, Xiaoping;Du, Chunmei;Huang, Huiqin;Gu, Hanjie;Dong, Xiwen;Hu, Yonghua. And the article was included in Aquaculture in 2022.Recommanded Product: 62893-19-0 This article mentions the following:

Two-component regulatory systems (TCSs) are omnipresent in Gram-neg. bacteria and play a major role in response to changes in environmental cues and pathogenicity. Edwardsiella piscicida is a serious pathogen of fresh and seawater aquaculture industries and has attracted increasing attention. However, extremely limited TCSs have been reported in E. piscicida. In this study, the role of response regulator OmpR which belongs to TCS EnvZ/OmpR was investigated in E. piscicida. By construction of a markerless ompR in-frame mutant strain, TX01螖ompR, we found that (i) in comparison to the wild type TX01, TX01螖ompR exhibited markedly compromised tolerance to acid stress, osmotic stress, and oxidative stress; (ii) the deletion of ompR significantly changed bacterial sensitivity to multiple antibiotics, (iii) the deficiency of ompR tremendously reduced bacterial motility, (iv) the deficiency of ompR abated bacterial colonization in host immune tissue and bacterial overall virulence. These results indicate OmpR is an important participant in E. piscicida adversity resistance and pathogenicity. As a response regulator, OmpR was demonstrated to downregulate acid resistance system cadBA and to upregulate the porin ompC and flagellum mediator flhDC. Taken together, our results illustrate that OmpR is a vital regulator that coordinates the expressions of multiple genes during the response to an adverse environment and invasion to host. In the experiment, the researchers used many compounds, for example, (6R,7R)-7-((R)-2-(4-Ethyl-2,3-dioxopiperazine-1-carboxamido)-2-(4-hydroxyphenyl)acetamido)-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (cas: 62893-19-0Recommanded Product: 62893-19-0).

(6R,7R)-7-((R)-2-(4-Ethyl-2,3-dioxopiperazine-1-carboxamido)-2-(4-hydroxyphenyl)acetamido)-3-(((1-methyl-1H-tetrazol-5-yl)thio)methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (cas: 62893-19-0) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Intermediate for a wide range of pharmaceuticals, polymers, dyes, corrosion inhibitors, rubber accelerators and surfactants.Recommanded Product: 62893-19-0

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Structural insights into inhibition of the bivalent menin-MLL interaction by small molecules in leukemia was written by Shi, Aibin;Murai, Marcelo J.;He, Shihan;Lund, George;Hartley, Thomas;Purohit, Trupta;Reddy, Gireesh;Chruszcz, Maksymilian;Grembecka, Jolanta;Cierpicki, Tomasz. And the article was included in Blood in 2012.Recommanded Product: 1271738-62-5 This article mentions the following:

Menin functions as a critical oncogenic cofactor of mixed lineage leukemia (MLL) fusion proteins in the development of acute leukemias, and inhibition of the menin interaction with MLL fusion proteins represents a very promising strategy to reverse their oncogenic activity. MLL interacts with menin in a bivalent mode involving 2 N-terminal fragments of MLL. In the present study, we reveal the first high-resolution crystal structure of human menin in complex with a small-mol. inhibitor of the menin-MLL interaction, MI-2. The structure shows that the compound binds to the MLL pocket in menin and mimics the key interactions of MLL with menin. Based on the menin-MI-2 structure, we developed MI-2-2, a compound that binds to menin with low nanomolar affinity (K_d = 22nM) and very effectively disrupts the bivalent protein-protein interaction between menin and MLL. MI-2-2 demonstrated specific and very pronounced activity in MLL leukemia cells, including inhibition of cell proliferation, down-regulation of Hoxa9 expression, and differentiation. Our results provide the rational and essential structural basis to design next generation of inhibitors for effective targeting of the menin-MLL interaction in leukemia and demonstrate a proof of concept that inhibition of complex multivalent protein-protein interactions can be achieved by a small-mol. inhibitor. In the experiment, the researchers used many compounds, for example, 4-(4-(5,5-Dimethyl-4,5-dihydrothiazol-2-yl)piperazin-1-yl)-6-propylthieno[2,3-d]pyrimidine (cas: 1271738-62-5Recommanded Product: 1271738-62-5).

4-(4-(5,5-Dimethyl-4,5-dihydrothiazol-2-yl)piperazin-1-yl)-6-propylthieno[2,3-d]pyrimidine (cas: 1271738-62-5) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Outside the body, piperazine has a remarkable power to dissolve uric acid and producing a soluble urate, but in clinical experience it has not proved equally successful. Recommanded Product: 1271738-62-5

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Discovery of a novel series of imidazo[1′,2′:1,6]pyrido[2,3-d]pyrimidin derivatives as potent cyclin-dependent kinase 4/6 inhibitors was written by Shi, Chen;Wang, Qian;Liao, Xuemei;Ge, Hui;Huo, Guoyong;Zhang, Leduo;Chen, Na;Zhai, Xiong;Hong, Yuan;Wang, Li;Wang, Zhe;Shi, Weijun;Mao, Yu;Yu, Jianxin;Ke, Ying;Xia, Guangxin. And the article was included in European Journal of Medicinal Chemistry in 2020.Quality Control of tert-Butyl 4-(4-aminobenzyl)piperazine-1-carboxylate This article mentions the following:

CDK4/6 has been identified as an attractive therapeutic target for treatment of cancer. For unmet clin. needs, a novel class of imidazo [1′,2′:1,6]pyrido [2,3-d]pyrimidin derivatives, which had distinctive triheteroaryl structure, had been discovered as CDK4/6 inhibitors. The compounds 10b (I) and 10c (II), displayed the low nanomolar range activities on CDK4/6, desirable antiproliferative activities, excellent metabolic properties, and acceptable pharmacokinetic characters. In Colo-205 and U87MG xenograft models, compounds 10b and 10c also showed significant tumor growth inhibitions with controllable toxicities. All data confirmed that imidazo [1′,2′:1,6]pyrido [2,3-d]pyrimidin derivatives 10b and 10c could be promising drug candidates for cancer therapy. In the experiment, the researchers used many compounds, for example, tert-Butyl 4-(4-aminobenzyl)piperazine-1-carboxylate (cas: 304897-49-2Quality Control of tert-Butyl 4-(4-aminobenzyl)piperazine-1-carboxylate).

tert-Butyl 4-(4-aminobenzyl)piperazine-1-carboxylate (cas: 304897-49-2) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Quality Control of tert-Butyl 4-(4-aminobenzyl)piperazine-1-carboxylate

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

A modified decision tree approach to improve the prediction and mutation discovery for drug resistance in Mycobacterium tuberculosis was written by Deelder, Wouter;Napier, Gary;Campino, Susana;Palla, Luigi;Phelan, Jody;Clark, Taane G.. And the article was included in BMC Genomics in 2022.Electric Literature of C43H58N4O12 This article mentions the following:

Drug resistant Mycobacterium tuberculosis is complicating the effective treatment and control of tuberculosis disease (TB). With the adoption of whole genome sequencing as a diagnostic tool, machine learning approaches are being employed to predict M. tuberculosis resistance and identify underlying genetic mutations. However, machine learning approaches can overfit and fail to identify causal mutations if they are applied out of the box and not adapted to the disease-specific context. We introduce a machine learning approach that is customized to the TB setting, which extracts a library of genomic variants re-occurring across individual studies to improve genotypic profiling. We developed a customized decision tree approach, called Treesist-TB, that performs TB drug resistance prediction by extracting and evaluating genomic variants across multiple studies. The application of Treesist-TB to rifampicin (RIF), isoniazid (INH) and ethambutol (EMB) drugs, for which resistance mutations are known, demonstrated a level of predictive accuracy similar to the widely used TB-Profiler tool (Treesist-TB vs. TB-Profiler tool: RIF 97.5% vs. 97.6%; INH 96.8% vs. 96.5%; EMB 96.8% vs. 95.8%). Application of Treesist-TB to less understood second-line drugs of interest, ethionamide (ETH), cycloserine (CYS) and para-aminosalisylic acid (PAS), led to the identification of new variants (52, 6 and 11, resp.), with a high number absent from the TB-Profiler library (45, 4, and 6, resp.). Thereby, Treesist-TB had improved predictive sensitivity (Treesist-TB vs. TB-Profiler tool: PAS 64.3% vs. 38.8%; CYS 45.3% vs. 30.7%; ETH 72.1% vs. 71.1%). Our work reinforces the utility of machine learning for drug resistance prediction, while highlighting the need to customize approaches to the disease-specific context. Through applying a modified decision learning approach (Treesist-TB) across a range of anti-TB drugs, we identified plausible resistance-encoding genomic variants with high predictive ability, while potentially overcoming the overfitting challenges that can affect standard machine learning applications. In the experiment, the researchers used many compounds, for example, 8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1Electric Literature of C43H58N4O12).

8-(n-(4-methyl-1-piperazinyl)formidoyl)-rifomycins (cas: 13292-46-1) belongs to piperazine derivatives. Piperazine is a fairly basic compound and is an amine solvent. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Electric Literature of C43H58N4O12

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Discovery of the Irreversible Covalent FGFR Inhibitor 8-(3-(4-Acryloylpiperazin-1-yl)propyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)-2-(methylamino)pyrido[2,3-d]pyrimidin-7(8H)-one (PRN1371) for the Treatment of Solid Tumors was written by Brameld, Ken A.;Owens, Timothy D.;Verner, Erik;Venetsanakos, Eleni;Bradshaw, J. Michael;Phan, Vernon T.;Tam, Danny;Leung, Kwan;Shu, Jin;LaStant, Jacob;Loughhead, David G.;Ton, Tony;Karr, Dane E.;Gerritsen, Mary E.;Goldstein, David M.;Funk, Jens Oliver. And the article was included in Journal of Medicinal Chemistry in 2017.Formula: C26H33N5O3 This article mentions the following:

Aberrant signaling of the FGF/FGFR pathway occurs frequently in cancers and is an oncogenic driver in many solid tumors. Clin. validation of FGFR as a therapeutic target has been demonstrated in bladder, liver, lung, breast, and gastric cancers. Our goal was to develop an irreversible covalent inhibitor of FGFR1-4 for use in oncol. indications. An irreversible covalent binding mechanism imparts many desirable pharmacol. benefits including high potency, selectivity, and prolonged target inhibition. Herein we report the structure-based design, medicinal chem. optimization, and unique ADME assays of our irreversible covalent drug discovery program which culminated in the discovery of compound 34 (PRN1371), a highly selective and potent FGFR1-4 inhibitor. In the experiment, the researchers used many compounds, for example, rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3Formula: C26H33N5O3).

rel-N-(5-(3,5-Dimethoxyphenethyl)-1H-pyrazol-3-yl)-4-((3R,5S)-3,5-dimethylpiperazin-1-yl)benzamide (cas: 1035270-39-3) belongs to piperazine derivatives. Industrial applications of piperazine include the manufacture of plastics, resins, pesticides and brake fluids. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Formula: C26H33N5O3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

A new dried blood spot LC-MS/MS method for therapeutic drug monitoring of palbociclib, ribociclib, and letrozole in patients with cancer was written by Poetto, Ariana Soledad;Posocco, Bianca;Gagno, Sara;Orleni, Marco;Zanchetta, Martina;Iacuzzi, Valentina;Canil, Giovanni;Buzzo, Mauro;Montico, Marcella;Guardascione, Michela;Basile, Debora;Pelizzari, Giacomo;Alberti, Martina;Gerratana, Lorenzo;Puglisi, Fabio;Toffoli, Giuseppe. And the article was included in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences in 2021.Electric Literature of C23H30N8O This article mentions the following:

Therapeutic drug monitoring TDM is strongly suggested to define the proper drug dosage to overcome inter- and intra-patient variability in drug exposure, which is typically observed with oral anticancer agents, such as palbociclib PALBO, ribociclib RIBO and letrozole LETRO, all approved for the treatment of HR+, HER2- locally advanced or metastatic breast cancer BC. Optimal TDM implementation requires a blood sampling organization that can be hampered by limited availability of health and laboratory personnel. Dried Blood Spot DBS sampling is proposed to overcome such limitations. The aim of this work was the development of a new LC-MS/MS method to analyze DBS samples containing PALBO, RIBO, and LETRO. Analytes extraction from DBS was performed by adding a methanolic solution containing the corresponding internal standards LC-MS/MS anal. was performed using a LC Nexera Shimadzu system coupled with an API 4000 QTrap SCIEX mass spectrometer. The chromatog. separation was performed on a Luna Omega Polar C18 column Phenomenex. The method was applied to 38 clin. samples collected by finger prick. The influence of hematocrit and spot size, sample homogeneity, stability, and correlation between finger prick and venous DBS measurement were assessed. The anal. validation was performed according to EMA and FDA guidelines. The anal. range of the method was 1 to 250 ng/mL for PALBO, 40 to 10000 ng/mL for RIBO, and 2 to 500 ng/mL for LETRO, where linearity was assessed, obtaining mean coefficients of determination R2 of 0.9979 for PALBO, 0.9980 for RIBO, and 0.9987 for LETRO. The LC-MS/MS method runtime was 6.6 min. Incurred sample reanal. demonstrated reproducibility, as the percentage difference between the two quantifications was lower than 20% for 100% of PALBO, 81.8% of RIBO, and 90.9% of LETRO paired samples. Intra- and inter-day precision CV % was lower than 11.4% and intra- and inter-day accuracy was between 90.0 and 106.5%. DBS sample stability at room temperature was confirmed for 2.5 mo. A pos. correlation was observed between DBS and plasma concentrations for the 3 drugs, Lins concordance correlation coefficients obtained by DBS normalization applying a selected strategy were 0.958 for PALBO, 0.957 for RIBO, and 0.963 for LETRO. In conclusion, a fast, easy, and reproducible DBS LC-MS/MS method for the simultaneous quantification of palbociclib; ribociclib and letrozole was developed to be used in clin. practice. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Electric Literature of C23H30N8O).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Although many piperazine derivatives occur naturally, piperazine itself can be synthesized by reacting alcoholic ammonia with 1,2-dichloroethane, by the action of sodium and ethylene glycol on ethylene diamine hydrochloride, or by reduction of pyrazine with sodium in ethanol.Electric Literature of C23H30N8O

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Development of validated spectrofluorimetric method for the estimation of buclizine hydrochloride from the tablet dosage form was written by Suganthi, A.;Fathimunnisa, A.;Sumithra, S.;Ravi, T. K.. And the article was included in Indo American Journal of Pharmaceutical Research in 2016.Application of 129-74-8 This article mentions the following:

Buclizine hydrochloride from its tablet dosage form was estimated by developing a novel validated indirect spectrofluorimetric method. Here the Buclizine hydrochloride was derivatized into nitro compound using nitrating mixture with an aid of heat which showed good fluorescence in water at 446 nm after excited at 350 nm. The calibration graph showed linear over the range 200-1000 ng/mL. The assay of buclizine hydrochloride in marketed formulations was found to be 98.96 卤 0.1586. Recovery values were close to 100% with the % RSD values of 0.432% and 0.673% at 50% and 100% level resp. From the results of validation it was observed that the method was found to be simple, accurate, sensitive and reproducible. Hence the proposed method can be used for routine quality control anal. In the experiment, the researchers used many compounds, for example, 1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride (cas: 129-74-8Application of 129-74-8).

1-(4-(tert-Butyl)benzyl)-4-((4-chlorophenyl)(phenyl)methyl)piperazine dihydrochloride (cas: 129-74-8) belongs to piperazine derivatives. Piperazine was first introduced as an anthelmintic in 1953. Piperazine compounds mediate their anthelmintic action by generally paralyzing parasites, allowing the host body to easily remove or expel the invading organism. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Application of 129-74-8

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Ultrasound-assisted dispersive liquid-liquid microextraction for determination of enrofloxacin in surface waters was written by Dias, Reyla A. S.;Sousa, Eliane R.;Silva, Gilmar S.;Silva, Lanna K.;Freitas, Arlan S.;Lima, Diana L. D.;Sousa, Erika M. L.. And the article was included in Microchemical Journal in 2021.Synthetic Route of C20H17F2N3O3 This article mentions the following:

This work describes the development of an HPLC-FLD methodol. for the separation of five fluoroquinolones (ciprofloxacin, enrofloxacin, sarafloxacin, norfloxacin and levofloxacin) followed by optimization of the DLLME process for the clean-up and preconcentration of enrofloxacin in samples of seawater and river water. The mobile phase used for the chromatog. separation consisted of methanol: phosphate buffer (NaHPO4 H2O 0.04 M pH 3 with H3PO4 85%), gradient eluted at a ratio of 20:80 (v:v). The mobile phase flow was maintained at 1.2 mL min-1. For the ultrasonic-assisted dispersive liquid-liquid microextraction (UA-DLLME), the following conditions were used: 8 mL of sample with pH adjusted to 8, extraction solvent: 500渭L of chloroform, dispersive solvent: 500渭L of acetonitrile; samples were vortexed and sonicated for 2 min, each. The enrichment factor (EF) was 54.7 and the recovery was 70%, achieving a limit of detection (LOD) of 0.11渭g L-1. Repeatability and intermediate reproducibility presented values of relative standard deviation (RSD) lower than 2%. Finally, the optimized method was applied to the anal. of water and enrofloxacin was detected in both water samples with a concentration of 0.20渭g L-1 in the river and 0.12渭g L-1 in the seawater. However, recovery tests performed to evaluate the water matrixes’ effects on the extraction performance, presented recoveries of 72 卤 6.1 for river water and 27 卤 8.3 for seawater. These results demonstrate that hereby developed method is only suitable for water samples with a low salinity content. In the experiment, the researchers used many compounds, for example, 6-Fluoro-1-(4-fluorophenyl)-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (cas: 98105-99-8Synthetic Route of C20H17F2N3O3).

6-Fluoro-1-(4-fluorophenyl)-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid (cas: 98105-99-8) belongs to piperazine derivatives. Simple N-substituted piperazines have been found in many drug molecules. Two common salts in the form of which piperazine is usually prepared for pharmaceutical or veterinary purposes are the citrate, 3C4H10N2.2C6H8O7 (i.e. containing 3 molecules of piperazine to 2 molecules of citric acid), and the adipate, C4H10N2.C6H10O4 (containing 1 molecule each of piperazine and adipic acid).Synthetic Route of C20H17F2N3O3

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

Perception and experience of oncologists regarding vaccination of cancer patients on active treatment was written by Hussien, Nervana;Eldin, Mai Ezz;Abdelaziz, Ahmed;Shaheen, Haitham;El-Kassas, Mohamed;Elzayat, Ibrahim;Elkhatib, Walid F.;Ahmed, Soha. And the article was included in International Journal of Cancer and Biomedical Research in 2022.Formula: C23H30N8O This article mentions the following:

The COVID-19 epidemic has wreaked havoc on individuals of all ages throughout the world. I In unprecedented time frame, its vaccination has been produced and made available to the general population. However, due to varying levels of its acceptance, vaccination did not gain widespread adoption. We aimed to measure the perception and experience of oncologists towards COVID19 vaccination in cancer patients on active therapy. A cross-sectional survey with a self-administered questionnaire was circulated among oncol. specialists in Egypt between Sept. – and Dec. 2021. A total of 83 respondents participated of which 59% had more than 10 years of experience in the oncol. field. The majority of the respondents 75 (90.4%) recommended giving the vaccine once available in case of hormonal treatment meanwhile the lowest percentage 32 (38.5%) was for anti CD20 monoclonal antibody, either as a single agent or combined with chemotherapy. Choices of 49 (59%), 46 (55%), and 43 (51.8%) to vaccinate patients on active treatment with cytotoxic chemotherapy, MoAb (except anti CD20), and immunotherapy resp. were reported. The inactivated COVID-19 virus vaccine was recommended by 39 (47%), followed by Vector vaccines in 20 (24.1%), 8 (9.6%) for the mRNA (mRNA) vaccines, while 16(19.3%) of them were undecided. Thirty-nine (47%) of the participants reported that patients on active treatment developed side effects from vaccination. The most conveyed side effects were fatigue in 34 (87%), fever or a local reaction each in 28 (71.8%), headache and myalgia equally in 19 (48.7%), and chills in 11 (28.2%), and myalgia in10 (25.6%). Strategies to address the practicality of dealing with vaccination in cancer patients are needed. Emphasis on the installation of the latest data in caring for this population and increased awareness of the services provided is crucial. Surveys are a useful tool reflecting real-world practice. In the experiment, the researchers used many compounds, for example, 7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3Formula: C23H30N8O).

7-Cyclopentyl-N,N-dimethyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (cas: 1211441-98-3) belongs to piperazine derivatives. Piperazine causes primary dermal irritation and skin burns at high concentrations. Piperazine also causes eye irritation in humans. Piperazines are very broad chemical group, covering a wide range of drugs from antidepressants to antihistamines. The connecting property of all these chemicals is the presence of a piperazine functional group.Formula: C23H30N8O

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics

The combination of Nutlin-3 and Tanshinone IIA promotes synergistic cytotoxicity in acute leukemic cells expressing wild-type p53 by co-regulating MDM2-P53 and the AKT/mTOR pathway was written by Guo, Yong;Li, Yi;Wang, Fang-Fang;Xiang, Bing;Huang, Xiao-Ou;Ma, Hong-Bing;Gong, Yu-Ping. And the article was included in International Journal of Biochemistry & Cell Biology in 2019.Electric Literature of C30H30Cl2N4O4 This article mentions the following:

The overexpression of mouse double minute 2 (MDM2) causes the inactivation of p53 in acute leukemia. MDM2 inhibitors that activate p53 and induce apoptosis are currently being developed for potential treatment of acute leukemia. Combining other drugs to enhance the efficacy of MDM2 inhibitors is the thus considered as a potential treatment scheme. Here, we report that the combination of Nutlin-3 and Tanshinone IIA synergistically induces cytotoxicity, cell cycle arrest, apoptosis, and autophagic cell death, thereby imparting anti-leukemia effect in an acute leukemia cell line with wild-type p53 by effectively activating p53, inhibiting the AKT/mTOR pathway, and activating the RAF/MEK pathway. Using primary samples from acute leukemia patients, we show that the combination of Nutlin-3 plus Tanshinone IIA synergistically induces cytotoxicity by activating p53 and inhibiting the AKT/mTOR pathway. This specific combination of Nutlin-3 and Tanshinone IIA is also effective in preventing the recurrence of refractory leukemia, such as Ph+ ALL with the ABL kinase T315I mutation and AML with the FLT3-ITD mutation. Taken together, the results of this study demonstrate that the Nutlin-3 plus Tanshinone IIA combination exerts synergistic anti-leukemia effects by regulating the p53 and AKT/mTOR pathways, although further investigation is warranted. Small-mol. MDM2 antagonists plus Tanshinone IIA may thus be a promising strategy for the treatment of acute leukemia. In the experiment, the researchers used many compounds, for example, 4-(cis-4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one (cas: 548472-68-0Electric Literature of C30H30Cl2N4O4).

4-(cis-4,5-Bis(4-chlorophenyl)-2-(2-isopropoxy-4-methoxyphenyl)-4,5-dihydro-1H-imidazole-1-carbonyl)piperazin-2-one (cas: 548472-68-0) belongs to piperazine derivatives. Piperazine belongs to the family of medicines called anthelmintics. Piperazine is formed as a co-product in the ammoniation of 1,2-dichloroethane or ethanolamine. These are the only routes to the chemical used commercially.Electric Literature of C30H30Cl2N4O4

Referemce:
Piperazine – Wikipedia,
Piperazines – an overview | ScienceDirect Topics