Month: October 2022

On July 31, 2020, Adiwidjaja, Jeffry; Boddy, Alan V.; McLachlan, Andrew J. published an article.Application In Synthesis of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile The title of the article was Physiologically-Based Pharmacokinetic Predictions of the Effect of Curcumin on Metabolism of Imatinib and Bosutinib: In Vitro and In Vivo Disconnect. And the article contained the following:

Abstract: Purpose: This study aimed to investigate the potential pharmacokinetic interactions between curcumin, imatinib and bosutinib, combining In Vitro and in silico methods. Methods: In Vitro metabolism of imatinib and bosutinib were investigated in pooled human liver microsomes and recombinant CYP3A4 enzyme in the presence and absence of curcumin and curcumin glucuronide using an LC-MS/MS assay for N-desmethyl metabolites. A physiol.-based pharmacokinetic (PBPK) model for curcumin formulated as solid lipid nanoparticles (SLN) was constructed using In Vitro glucuronidation kinetics and published clin. pharmacokinetic data. The potential effects of curcumin coadministration on systemic exposures of imatinib and bosutinib were predicted in silico using PBPK simulations. Results: Curcumin demonstrated potent reversible inhibition of cytochrome P 450 (CYP)3A4-mediated N-demethylation of imatinib and bosutinib and CYP2C8-mediated metabolism of imatinib with inhibitory constants (ki,u) of ≤1.5μmol. L-1. A confirmatory In Vitro study with paclitaxel, the 6α-hydroxylation of which is exclusively mediated by CYP2C8, was consistent with a potent inhibition of this enzyme by curcumin. Curcumin glucuronide also inhibited both CYP enzymes In Vitro, albeit to a lesser extent than that of curcumin. PBPK model simulations predicted that at recommended dosing regimens of SLN curcumin, coadministration would result in an increase in systemic exposures of imatinib and bosutinib of up to only 10%. Conclusion: A PBPK model for curcumin in a SLN formulation was successfully developed. Although curcumin possesses a strong In Vitro inhibitory activity towards CYP3A4 and CYP2C8 enzymes, its interactions with imatinib and bosutinib were unlikely to be of clin. importance due to curcumin’s poor bioavailability. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Application In Synthesis of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

The Article related to mol modeling simulation drug interaction pharmacokinetic pbpk, bosutinib, curcumin, imatinib, modelling and simulation, natural product-drug interactions, physiologically-based pharmacokinetic (pbpk) and other aspects.Application In Synthesis of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

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

On August 10, 2022, Wang, Linqiong; Li, Yi; Zhao, Zhe; Zhu, Mengjie; Hu, Tong published an article.Reference of 1-Cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid hydrochloride hydrate The title of the article was Tidal flat aquaculture pollution governs sedimentary antibiotic resistance gene profiles but not bacterial community based on metagenomic data. And the article contained the following:

Coastal tidal flats are intersection zones between terrestrial and marine environments and are considered repositories of pollutants from anthropogenic activities (e.g., fishery and aquaculture). Specifically, the prevalence of antibiotics and antibiotic resistance genes (ARGs) in coastal aquaculture environments pose critical threats to estuarine ecosystems. However, the contribution of aquaculture to the occurrence and abundance of ARGs and community assemblies has not been fully explored in tidal flat zones. Thus, we investigated ARGs profiles, ARG-carrying host bacteria, and their associate microbial community in the Dongtai and Sheyang tidal flat aquaculture regions of Jiangsu, China using metagenomic assembly methods. The antibiotic concentrations in the sediment samples ranged from nd to 35.50 ng/g dw, and the antibiotic pollution in the Dongtai tidal flat was more severe than in the Sheyang tidal flats. Metagenomic assembly indicated that a total of 247 ARG subtypes associated with ARG 33 types were characterized across all samples and their abundance in the Dongtai region exceeded that in the Sheyang region. Meanwhile, 21 bacteria in the tidal flat aquaculture were identified as ARG-carrying pathogens, including Escherichia coli, Vibrio fluvialis, and Staphylococcus aureus. Using neutral and null modeling anal. to determine the community ecol. processes, the results revealed bacterial and ARG communities were generally dominated by stochastic and deterministic processes, resp. The above results suggested that aquaculture pollution was contributed to shape ARG profiles in tidal flats. The observed deterministic processes affecting the ARG community in tidal flat aquaculture also provides an effective foundation to control the risks of environmental antibiotic resistance through reducing aquaculture antibiotic usage. The experimental process involved the reaction of 1-Cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid hydrochloride hydrate(cas: 86393-32-0).Reference of 1-Cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid hydrochloride hydrate

The Article related to antibiotic resistance gene bacterial community metagenomic data aquaculture pollution, arg host bacteria, antibiotic resistance genes, ecological processes, metagenomic assembly, tidal flat aquaculture and other aspects.Reference of 1-Cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid hydrochloride hydrate

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

On April 30, 2004, Liang, Shuang; Liu, Chaomei; Jin, Yongsheng; He, Qiuqin published an article.Formula: C12H16N2O2 The title of the article was Synthesis and antifungal activity of 1-(1H-1,2,4-triazol-1-yl)-2-(2,4-difluorophenyl)-3-[(4-substituted)-1-piperazinyl]-2-propanols. And the article contained the following:

The effect of the side chain in (4-substituted)-1-piperazinyl on the antifungal activity of fluconazole compounds was studied. Thirteen title compounds were synthesized and confirmed by the elementary anal., 1H-NMR and IR spectra. The MICs of all the title compounds were determined by the method recommended by the National Committee for Clin. Laboratory Standards (NCCLS) using the RPMI1640 test medium. The results of the preliminary antifungal test showed that all the title compounds exhibited potent antifungal activities. The activities of the eight compounds thus prepared were more than 4 times as high as that of fluconazole and equal to that of ketoconazole against Candida albicans in vitro. The lipid/water distribution coefficient and stereochem. have important influence on the antifungal activities of the title compounds The experimental process involved the reaction of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone(cas: 67914-60-7).Formula: C12H16N2O2

The Article related to triazole piperazine difluorophenyl preparation antifungal agent, lipid water distribution coefficient stereochem antifungal, structure activity fungicidal triazole piperazine difluorophenyl preparation and other aspects.Formula: C12H16N2O2

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

On December 31, 2021, Ma, Chen-En; Ghosh, Sunita; Leyshon, Catherine; Blosser, Nikki; Dersch-Mills, Deonne; Jupp, Jennifer; Savoie, Lynn; Liew, Elena; Jamani, Kareem published an article.Computed Properties of 380843-75-4 The title of the article was Clinical outcome of chronic myeloid leukemia patients who switch from first-line therapy with a second generation tyrosine kinase inhibitor to an alternative TKI. And the article contained the following:

While second generation tyrosine kinase inhibitors (2GTKIs) are highly effective therapies for chronic myeloid leukemia (CML), a significant minority of patients who initiate a 2GTKI will require a switch to an alternative TKI. The long-term outcomes of those who require a change in therapy after front-line 2GTKI therapy are largely undescribed. Here we describe the clin. outcomes associated with switch to an alternative TKI after first-line therapy with a 2GTKI. Of 232 patients who initiated a 2GTKI during the study period, 76 (33%) switched to an alternative TKI. Reasons for switching included intolerance (79%) and resistance (21%). Among the 60 patients who switched due to intolerance, 53 (88%) were able to achieve or maintain a major mol. response (MMR) with 5-yr progression-free survival (PFS) 90.5% (95% CI 90.4-90.6%). Amongst the 16 patients who switched due to resistance, 8 patients (50%) were able to achieve MMR with 5-yr PFS 80.4% (95% CI 80.2-80.6%). Most patients who switched due to intolerance remained on their second-line TKI. Approx. 25% of patients who initiate first-line 2GTKI in a real world setting will ultimately switch to an alternate TKI due to intolerance. Patients who switch for intolerance continue to enjoy excellent clin. outcomes. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Computed Properties of 380843-75-4

The Article related to dasatinib nilotinib anticancer agent chronic myeloid leukemia, chronic myeloid leukemia, chronic phase chronic myeloid leukemia, dasatinib, nilotinib, second generation tyrosine kinase inhibitor, switch and other aspects.Computed Properties of 380843-75-4

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

On May 31, 2022, Robin, J. B.; Theron, A.; Quittet, P.; Exbrayat, C.; Gaillard, J. B.; Lavabre-Bertrand, T.; David, S.; Saad, A.; Jourdan, E.; Cartron, G. published an article.Application of 380843-75-4 The title of the article was Discontinuation of tyrosine kinase inhibitor in chronic myeloid leukemia: a retrospective cohort in East Occitania. And the article contained the following:

Tyrosine kinase inhibitor (TKI) discontinuation in chronic phase chronic myeloid leukemia (CML) patients has been examined in a real-life setting in the east occitania region of France. We have collected sex, age, prognostic scores, pre-TKI treatment, TKI length and response, relapse data from patients who had stopped TKI in prolonged complete mol. remission (CMR), and analyzed relapse risk factors. Sixty consecutive patients were included from Jan. 2010 to Dec. 2016. Sixteen received pre-TKI treatment. Fifty-three received a first-generation TKI, and seven had a second-generation TKI in first-line therapy. The median TKI time to achieve CMR was 20.5 mo [5-137]. The median TKI length before discontinuation treatment was 73 mo [12-158]. Twenty-two patients (37%) relapsed with a median time to relapse of 6 mo [3-27]. An intermediate or high Sokal score was the only relapse risk factor (HR = 3.32, p < 0.05) associated with relapse after TKI discontinuation. TKI discontinuation was possible without relapse for half of the patients in chronic phase CML. In a real-life cohort, a high-risk Sokal score at diagnosis appears to be an adverse prognosis feature for TKI discontinuation. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Application of 380843-75-4

The Article related to chronic myeloid leukemia recurrence tyrosine kinase inhibitor discontinuation france, chronic myeloid leukemia, complete molecular response, molecular recurrence-free remission, tyrosine kinase inhibitor and other aspects.Application of 380843-75-4

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

On May 31, 2020, Nadaf, Afra Quasar A.; Najare, Mahesh S.; Garbhagudi, Manjunatha; Mantur, Shivaraj; Sunagar, Manjunath G.; Gaonkar, Supreet; Joshi, Shrinivas; Khazi, Imtiyaz Ahmed M. published an article.Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone The title of the article was Synthesis of 6-[4-(4-Propoxyphenyl)piperazin-1-yl]-9H-purine Derivatives as Antimycobacterial and Antifungal Agents: In Vitro Evaluation and In Silico Study. And the article contained the following:

A series of novel alkyl substituted purines were synthesized. 6-[4-(4-Propoxyphenyl)piperazin-1-yl]-9H-purine was used as the key starting material, which was synthesized via a multistep protocol and finally subjected for N-alkylation with various alkyl halides with an aim to get prospective antimicrobial agents. The structures of the novel compounds were established by substantiating them through spectral techniques like 1H-NMR, 13C-NMR, FT-IR and EI-MS. They were explored for antitubercular activity against Mycobacterium tuberculosis H37RV. Furthermore, they were checked for their antimicrobial activity concerning bacterial and fungal strains. The title compounds exhibited considerable antimicrobial activity without any significant toxicity. In silico studies depicted their good binding profile against Mycobacterium tuberculosis enoyl reductase (InhA; PDB ID: 4TZK) and Candida albicans dihydrofolate reductase (PDB ID: 1AI9). The title compounds obeyed Lipinski’s parameters and have exhibited good drug-like properties. The experimental process involved the reaction of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone(cas: 67914-60-7).Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone

The Article related to propoxyphenyl piperazinyl purine preparation antimicrobial antibacterial antifungal, mycobacterium tuberculosis, docking study, antimicrobial activity, antitubercular activity, propoxyphenylpiperazin-1-yl and other aspects.Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone

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

On August 31, 2022, Yokoyama, Yuta; Nozawa, Eiji; Morita, Miho; Ishikawa, Emi; Mori, Takehiko; Sakurai, Masatoshi; Kikuchi, Taku; Matsuki, Eri; Yamazaki, Rie; Kataoka, Keisuke; Jibiki, Aya; Kawazoe, Hitoshi; Suzuki, Sayo; Nakamura, Tomonori published an article.Category: piperazines The title of the article was Simultaneous quantification of dasatinib, nilotinib, bosutinib, and ponatinib using high-performance liquid chromatography-Photodiode array detection. And the article contained the following:

Dasatinib, nilotinib, and bosutinib, second-generation tyrosine kinase inhibitors (TKIs), and ponatinib, a third-generation TKI, are approved pharmaceuticals used in the treatment of chronic myeloid leukemia (CML). Although liquid chromatog.-tandem mass spectrometry assays for simultaneous quantification of the four TKIs in human serum have been reported in the literature, a high-performance liquid chromatog. (HPLC) assay that simultaneously quantifies these compounds has not yet been developed. This study aims to establish and validate an efficient HPLC anal. method using a photodiode array (PDA) detector for the simultaneous quantification of the four TKIs. Calibration standards were prepared by serial dilution of serum samples containing the four TKIs, followed by solid-phase extraction The four TKIs were eluted in order within 10 min using a binary HPLC gradient system. The calibration ranges were 2-500 ng/mL for dasatinib, 100-5000 ng/mL for nilotinib, and 10-500 ng/mL for bosutinib and ponatinib. Intra-day and inter-day precision and accuracy values were found to be in accordance with the U. S. Food and Drug Administration guidelines. The recovery rates were 92.9%-96.0%, 80.7%-86.1%, 91.6%-99.0%, and 86.4%-92.6% for dasatinib, nilotinib, bosutinib, and ponatinib, resp. To the best of our knowledge, this is the first report of an HPLC-PDA anal. method that allows efficient simultaneous quantification of the four TKIs in the serum of patients with CML. We believe that the method developed herein can improve the efficiency of therapeutic drug monitoring in patients with CML in clin. practice. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Category: piperazines

The Article related to photodiode dasatinib nilotinib bosutinib ponatinib high performance liquid chromatog, chronic myeloid leukemia, high-performance liquid chromatography, photodiode array detector, tyrosine kinase inhibitor and other aspects.Category: piperazines

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

On October 31, 2005, He, Qiuqin; Liu, Chaomei; Men, Xiufeng; Zhao, Jingxia published an article.Electric Literature of 67914-60-7 The title of the article was Synthesis and antifungal activity of 1-(1H-1,2,4-triazol-1-yl)-2-(3,3-dimethyl)-3-[(4-substituted)-1-piperazinyl]-2-propanol derivatives. And the article contained the following:

Antifungal activity of triazole derivatives bearing a side chain containing tert-Bu and 4-[4-(alkoxy)phenyl]-1-piperazine was studied and their antifungal activities were compared with that of fluconazole and itraconazole. According to the structure of fluconazole, ten target compounds were designed and synthesized. The target compounds thus prepared included α-(1,1-dimethylethyl)-4-[4-(pyridinylmethoxy)phenyl]-α-[(1H-1,2,4-triazolyl)methyl]-1-piperazineethanol isomers, α-(1,1-dimethylethyl)-4-[4-[(2-methylphenyl)methoxy]phenyl]-α-[(1H-1,2,4-triazolyl)methyl]-1-piperazineethanol, α-(1,1-dimethylethyl)-4-(4-ethoxyphenyl)-α-[(1H-1,2,4-triazolyl)methyl]-1-piperazineethanol, etc. The MIC80 of all the target compounds were determined by the method recommended by the national committee for clin. laboratory standards (NCCLS) using the RPMI-1640 test medium. All the target compounds were firstly reported. The results of the preliminary antifungal test showed that all the target compounds had potent antifungal activities to a certain extent. The activities of four target compounds were 4 times as high as that of fluconazole and equal to that of itraconazole against Candida albicans in vitro. More hydrophobic groups can be introduced to design triazole compounds and stereochem. have important influence on the antifungal activities of the target compounds The experimental process involved the reaction of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone(cas: 67914-60-7).Electric Literature of 67914-60-7

The Article related to butyl triazole antifungal activity, piperazineethanol pyridinylmethoxy phenyl triazolylmethyl preparation antifungal agent, triazolylmethyl alkoxyphenylmethyl piperazineethanol preparation antifungal agent and other aspects.Electric Literature of 67914-60-7

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

On July 15, 2020, Ramesh, Deepthi; Joji, Annu; Vijayakumar, Balaji Gowrivel; Sethumadhavan, Aiswarya; Mani, Maheswaran; Kannan, Tharanikkarasu published an article.SDS of cas: 67914-60-7 The title of the article was Indole chalcones: Design, synthesis, in vitro and in silico evaluation against Mycobacterium tuberculosis. And the article contained the following:

Indole chalcones were designed and synthesized as a promising set of compounds against H37Rv strain of Mycobacterium tuberculosis. Within this library of compounds, (E)-1-(furan-3-yl)-3-(1H-indol-3-yl)prop-2-en-1-one (18), (E)-3-(1H-indol-3-yl)-1-(thiophen-2-yl)prop-2-en-1-one (20) and (E)-2-((1H-indol-2-yl)methylene)cyclopentan-1-one (24) displayed high anti-tubercular activity at 50 μg/mL with MIC values of 210, 197 and 236 μM resp. The in-silico studies revealed that compound 18 exhibit binding modes similar to FAS-II inhibitors like INH or Thiolactomycin against KasA protein. Cytotoxicity assay results suggest that the compounds 18, 20 and 24 are non-cytotoxic to human megakaryocytes and murine B cells. The experimental process involved the reaction of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone(cas: 67914-60-7).SDS of cas: 67914-60-7

The Article related to indole chalcones tuberculostatics mycobacterium, anti-tubercular, cytotoxicity, h(37)rv strain, indole chalcones, kasa protein, luciferase reporter mycobacteriophages (lrp), mycobacterium tuberculosis, sars and other aspects.SDS of cas: 67914-60-7

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

Deb, Suryyani; Boknaes, Niklas; Sjoestroem, Clara; Tharmakulanathan, Anjana; Lotfi, Kourosh; Ramstroem, Sofia published an article in 2020, the title of the article was Varying effects of tyrosine kinase inhibitors on platelet function-A need for individualized CML treatment to minimize the risk for hemostatic and thrombotic complications?.Category: piperazines And the article contains the following content:

Since their introduction, tyrosine kinase inhibitors (TKIs, eg, imatinib, nilotinib, dasatinib, bosutinib, ponatinib) have revolutionized the treatment of chronic myeloid leukemia (CML). However, long-term treatment with TKIs is associated with serious adverse events including both bleeding and thromboembolism. Exptl. studies have shown that TKIs can cause platelet dysfunction. Herein, we present the first side-by-side investigation comparing the effects of currently used TKIs on platelet function and thrombin generation when used in clin. relevant concentrations A flow cytometry multiparameter protocol was used to study a range of significant platelet activation events (fibrinogen receptor activation, alpha granule, and lysosomal exocytosis, procoagulant membrane exposure, and mitochondrial permeability changes). In addition, thrombin generation was measured in the presence of TKIs to assess the effects on global hemostasis. Results show that dasatinib generally inhibited platelet function, while bosutinib, nilotinib, and ponatinib showed less consistent effects. In addition to these general trends for each TKI, we observed a large degree of interindividual variability in the effects of the different TKIs. Interindividual variation was also observed when blood from CML patients was studied ex vivo with whole blood platelet aggregometry, free oscillation rheometry (FOR), and flow cytometry. Based on the donor responses in the side-by-side TKI study, a TKI sensitivity map was developed. We propose that such a sensitivity map could potentially become a valuable tool to help in decision-making regarding the choice of suitable TKIs for a CML patient with a history of bleeding or atherothrombotic disease. The experimental process involved the reaction of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile(cas: 380843-75-4).Category: piperazines

The Article related to bosutinib nilotinib anticancer tyrosine kinase inhibitor platelet myeloid leukemia, chronic myeloid/myelogenous leukemia, coagulation, hemostasis, personalized medicine, platelets, tyrosine kinase inhibitors and other aspects.Category: piperazines

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