Month: October 2022

On October 31, 2019, Platania, Chiara Bianca Maria; Lazzara, Francesca; Fidilio, Annamaria; Fresta, Claudia Giuseppina; Conti, Federica; Giurdanella, Giovanni; Leggio, Gian Marco; Salomone, Salvatore; Drago, Filippo; Bucolo, Claudio published an article.Application of 1428327-31-4 The title of the article was Blood-retinal barrier protection against high glucose damage: The role of P2X7 receptor. And the article contained the following:

Blood retinal barrier (BRB) breakdown is a hallmark of diabetic retinopathy, whose occurrence in early or later phases of the disease has not yet been completely clarified. Recent evidence suggests that hyperglycemia induces activation of the P2X7 receptor (P2X7R) leading to pericyte cell death. We herein investigated the role of P2X7R on retinal endothelial cells viability and expression of tight- and adherens-junctions following high glucose (HG) exposure. We found that HG elicited P2X7R activation and expression and release of the pro-inflammatory cytokine IL-1β in human retinal endothelial cells (HRECs). Furthermore, HG exposure caused a decrease in HRECs viability and a damage of the BRB. JNJ47965567, a P2X7R antagonist, protected HRECs from HG-induced damage (LDH release) and preserved the BRB, as shown by transendothelial elec. resistance and cell junction morphol. (ZO-1, claudin-5 and VE-cadherin). Moreover, JNJ47965567 treatment significantly decreased IL-1β expression and release, elicited by HG. These data indicate that P2X7R plays an important role to regulate BRB integrity, in particular the block of this receptor was useful to counteract the damage elicited by HG in HRECs, and warranting further clin. evaluation of P2X7R antagonists for the treatment of diabetic macular edema. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).Application of 1428327-31-4

The Article related to p2x7 receptor antagonist blood retina barrier hyperglycemia diabetes retinopathy, blood retinal barrier, diabetic retinopathy, interleukin-1, p2x7 receptor antagonist, purinergic receptors and other aspects.Application of 1428327-31-4

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

Haguet, Helene; Bouvy, Celine; Delvigne, Anne-Sophie; Modaffari, Elise; Wannez, Adeline; Xue, Lixia published an article in 2020, the title of the article was The risk of arterial thrombosis in patients with chronic myeloid leukemia treated with second and third generation BCR-ABL tyrosine kinase inhibitors may be explained by their impact on endothelial cells: an in-vitro study.Product Details of 380843-75-4 And the article contains the following content:

BCR-ABL tyrosine kinase inhibitors (TKIs) revolutionized the treatment of chronic myeloid leukemia, inducing deep mol. responses, largely improving patient survival and rendering treatment-free remission possible. However, three of the five BCR-ABL TKIs, dasatinib, nilotinib, and ponatinib, increase the risk of developing arterial thrombosis. Prior investigations reported that nilotinib and ponatinib affect the endothelium, but the mechanisms by which they exert their toxic effects are still unclear. The impact of dasatinib and bosutinib on endothelial cells has been poorly investigated. Here, we aimed to provide an in vitro homogenous evaluation of the effects of BCR-ABL TKIs on the endothelium, with a special focus on the type of cell death to elucidate the mechanisms responsible for the potential cytotoxic effects of BCR-ABL TKIs nilotinib and ponatinib on endothelial cells. We tested the five BCR-ABL TKIs at three concentrations on human umbilical venous endothelial cells (HUVECs). This study highlights the endothelial toxicity of ponatinib and provides insights about the mechanisms by which it affects endothelial cell viability. Ponatinib induced apoptosis and necrosis of HUVECs after 72 h. Dasatinib affected endothelial cells in vitro by inhibiting their proliferation and decreased wound closure as soon as 24 h of treatment and even at infra-therapeutic dose (0.005μM). Comparatively, imatinib, nilotinib, and bosutinib had little impact on endothelial cells at therapeutic concentrations They did not induce apoptosis nor necrosis, even after 72 h of treatment but they inhibited HUVEC proliferation. Overall, this study reports various effects of BCR-ABL TKIs on endothelial cells and suggests that ponatinib and dasatinib induce arterial thrombosis through endothelial dysfunction. 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).Product Details of 380843-75-4

The Article related to human chronic myeloid leukemia arterial thrombosis tyrosine kinase endothelium, bcr-abl tyrosine kinase inhibitor, atherosclerosis, cardiovascular, chronic myeloid leukemia, endothelial cells and other aspects.Product Details of 380843-75-4

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

On September 23, 2010, Hansen, C. Henrik published a patent.Computed Properties of 890092-19-0 The title of the patent was Preparation of substituted 2-phenyl-3H-quinazolin-4-ones and analogs as antiinflammatory and cardiovascular agents. And the patent contained the following:

The invention is related to the preparation of 2-phenyl-3H-quinazolin-4-ones and analogs, e.g, 2-[4-(4-hydroxypiperidin-1-yl)phenyl]-5,7-dimethoxypyrido[2,3-d]pyrimidin-4(3H)-one (I), that are useful in regulating the expression of interleukin-6 (IL-6) and/or vascular cell adhesion mol.-1 (VCAM-1), and their use in the treatment and/or prevention of cardiovascular and inflammatory diseases and related disease states, such as atherosclerosis, asthma, arthritis, cancer, multiple sclerosis, psoriasis, and inflammatory bowel diseases, and autoimmune disease(s). Thus, cyclization of 2-amino-4,6-dimethoxynicotinamide with 4-(4-hydroxypiperidin-1-yl)benzaldehyde gave pyridopyrimidinone I which caused a ≥ 20% inhibition in IL-6 mRNA and in VCAM-1 mRNA at a concentration ≤ 10 μM. Pharmaceutical compositions containing title compounds are also disclosed. The experimental process involved the reaction of 4-(4-Acetylpiperazin-1-yl)benzaldehyde(cas: 890092-19-0).Computed Properties of 890092-19-0

The Article related to phenylquinazolinone preparation interleukin 6 proliferation inhibitor antiinflammatory cardiovascular, vascular cell adhesion mol 1 inhibitor phenylquinazolinone pyridopyrimidinone preparation and other aspects.Computed Properties of 890092-19-0

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

On June 30, 2022, Gunther, G.; Saathoff, E.; Rachow, A.; Ekandjo, H.; Diergaardt, A.; Marais, N.; Lange, C.; Nepolo, E. published an article.HPLC of Formula: 86393-32-0 The title of the article was Clinical evaluation of a line-probe assay for tuberculosis detection and drug-resistance prediction in Namibia. And the article contained the following:

Treatment of tuberculosis requires rapid information about Mycobacterium tuberculosis (Mtb) drug susceptibility to ensure effective therapy and optimal outcomes. At the tuberculosis referral hospital in Windhoek, Namibia, a country of high tuberculosis incidence, we evaluated the diagnostic accuracy of a line-probe-assay (LPA), GenID, for the mol. diagnosis of Mtb infection and drug resistance in patients with suspected tuberculosis (cohort 1) and confirmed rifampin (RIF)-resistant tuberculosis (cohort 2). GenID test results were compared to Xpert MTB/RIF and/or Mtb culture and antimicrobial suceptibilty testing. GenID LPA was applied to 79 and 55 samples from patients in cohort 1 and cohort 2, resp. The overall sensitivity of GenID LPA for the detection of Mtb DNA in sputum from patients with detectable and undetectable acid-fast bacilli by sputum smear microscopy was 93.3% (56/60; 95% confidence interval = 83.8-98.2) and 22.7% (5/22; 7.8-45.4). The sensitivity/specificity for the detection of drug resistance was 84.2% (32/38; 68.7-94.0)/100% (19/19; 82.4-100.0) for RIF, 89.7% (26/29; 72.6-97.8)/91.7% (22/24; 73.0-99.0) for isoniazid, and 85.7% (6/7; 42.1-99.6)/94.7% (18/19; 74.0-99.9) for fluoroquinolones; 23.6% of tests for second-line injectable resistance were invalid despite repeat testing. The diagnosis of tuberculosis by detection of Mtb DNA in sputum by GenID LPA depends strongly on the detection of acid-fast bacilli in sputum specimen. Prediction of drug resistance by GenID did not reach the World Health Organization (WHO) target product profile. 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).HPLC of Formula: 86393-32-0

The Article related to tuberculosis drug resistance line probe assay namibia, xpert mtb/rif, diagnostics, multi-drug resistant, mycobacterium tuberculosis, mycobacterium tuberculosis detection, second-line resistance and other aspects.HPLC of Formula: 86393-32-0

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

Cortes, Jorge E.; Kantarjian, Hagop M.; Mauro, Michael J.; An, Fiona; Nick, Sonja; Leip, Eric; Gambacorti-Passerini, Carlo; Bruemmendorf, Tim H. published an article in 2021, the title of the article was Long-term cardiac, vascular, hypertension, and effusion safety of bosutinib in patients with Philadelphia chromosome-positive leukemia resistant or intolerant to prior therapy.Name: 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile And the article contains the following content:

Long-term follow-up (≥4 years) demonstrated a low incidence of cardiac and vascular treatment-emergent adverse events (TEAEs) with bosutinib treatment. We evaluated cardiac, vascular, hypertension, and effusion TEAEs after ≥ 7 years of follow-up in patients with Philadelphia chromosome-pos. (Ph+) leukemia. This retrospective anal. of a phase I/II study and its ongoing extension study included data from patients with chronic phase chronic myeloid leukemia (CML) treated with bosutinib after resistance/intolerance to imatinib (CP2L) or to imatinib plus dasatinib and/or nilotinib (CP3L), and those with accelerated/blast phase CML or acute lymphoblastic leukemia after treatment with, at a min., imatinib (ADV). In all, 570 patients were treated with bosutinib; median treatment duration was 11.1 mo (range: 0.03-133.1). The incidence of cardiac, vascular, hypertension, and effusion-related TEAEs was 10.9%, 8.8%, 9.1%, and 13.3%, resp. Few patients had maximum grade 3-4 TEAEs (cardiac, 3.9%; vascular, 4.0%; hypertension, 3.0%; effusion, 4.6%). Grade 5 TEAEs occurred in the cardiac (0.7%) and vascular (1.8%) clusters only. In years 5-7, fewer than 5% of patients each year had newly occurring cardiac, vascular, hypertension, or effusion TEAEs. The exposure-adjusted TEAE rates (patients with TEAEs/total patient-year) pooled across CP2L, CP3L, and ADV cohorts were as follows: cardiac, 0.044; vascular, 0.035; hypertension, 0.038; and effusion, 0.056, of which, correspondingly, 0.9%, 1.2%, 0%, and 2.1% required treatment discontinuation. The incidence of cardiac, hypertension, vascular, and effusion events was low in patients with Ph+ CML resistant or intolerant to prior therapy who were treated with bosutinib. 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).Name: 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

The Article related to bosutinib drug safety toxicity philadelphia chromosome pos leukemia patient, bosutinib, cardiovascular events, chronic myeloid leukemia, clinical trial, effusion events, tyrosine kinase inhibitor and other aspects.Name: 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 July 31, 2020, Mulas, Olga; Caocci, Giovanni; Stagno, Fabio; Bonifacio, Massimiliano; Annunziata, Mario; Luciano, Luigiana; Orlandi, Ester Maria; Abruzzese, Elisabetta; Sgherza, Nicola; Martino, Bruno; Albano, Francesco; Galimberti, Sara; Pregno, Patrizia; Bocchia, Monica; Castagnetti, Fausto; Tiribelli, Mario; Binotto, Gianni; Gozzini, Antonella; Capodanno, Isabella; Fozza, Claudio; Luzi, Debora; Efficace, Fabio; Simula, Maria Pina; Scaffidi, Luigi; De Gregorio, Fiorenza; Elena, Chiara; Trawinska, Malgorzata Monika; Cattaneo, Daniele; Attolico, Imma; Barate, Claudia; Pirillo, Francesca; Sicuranza, Anna; Gugliotta, Gabriele; Stella, Rossella; Scalzulli, Emilia; Iurlo, Alessandra; Foa, Robin; Breccia, Massimo; La Nasa, Giorgio published an article.Category: piperazines The title of the article was Renin angiotensin system inhibitors reduce the incidence of arterial thrombotic events in patients with hypertension and chronic myeloid leukemia treated with second- or third-generation tyrosine kinase inhibitors. And the article contained the following:

Hypertension is a commonly reported comorbidity in patients diagnosed with chronic myeloid leukemia (CML), and its management represents a challenge in patients treated with 2nd- or 3rd-generation tyrosine kinase inhibitors (TKIs), considering their addnl. cardiovascular (CV) toxicity. The renin angiotensin system (RAS) contributes to hypertension genesis and plays an important role in atherosclerosis development, proliferation, and differentiation of myeloid hematopoietic cells. We analyzed a cohort of 192 patients with hypertension at CML diagnosis, who were treated with 2nd- or 3rd-generation TKIs, and evaluated the efficacy of RAS inhibitors (angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor blockers (ARBs)) in the prevention of arterial occlusive events (AOEs), as compared with other drug classes. The 5-yr cumulative incidence of AOEs was 32.7 ± 4.2%. Patients with SCORE ≥ 5% (high-very-high) showed a significantly higher incidence of AOEs (33.7 ± 7.6% vs 13.6 ± 4.8%, p = 0.006). The AOE incidence was significantly lower in patients treated with RAS inhibitors (14.8 ± 4.2% vs 44 ± 1%, p < 0.001, HR = 0.283). The difference in the low and intermediate Sokal risk group was confirmed but not in the high-risk group, where a lower RAS expression has been reported. Our data suggest that RAS inhibitors may represent an optimal treatment in patients with hypertension and CML, treated with 2nd or 3rdG TKIs. 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 anticancer ace inhibitor angiotensin receptor blocker thrombosis hypertension leukemia, arterial occlusive events, chronic myeloid leukemia, hypertension, renin angiotensin system inhibitors, tki and other aspects.Category: piperazines

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

On October 31, 2020, Romano, Giovanni Luca; Amato, Rosario; Lazzara, Francesca; Porciatti, Vittorio; Chou, Tsung-Han; Drago, Filippo; Bucolo, Claudio published an article.Reference of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide The title of the article was P2X7 receptor antagonism preserves retinal ganglion cells in glaucomatous mice. And the article contained the following:

To investigate the role of P2X7 receptor to preserve retinal ganglion cells (RGCs) structure and function in a genetic mouse model (DBA/2J mouse) of age-related glaucomatous neurodegeneration. Chronic treatment with P2X7 receptor antagonist eye drops was carried out in order to assess RGCs function and d. by pattern electroretinogram (PERG) and RBPMS immunostaining, resp. Further, microglia activation was assessed in flat-mounted retina by using Iba-1 immunostaining. Untreated glaucomatous eyes displayed significant microglia activation, alteration of PERG signal, and RGCs loss. In the P2X7 receptor antagonist-treated eyes, the PERG signal was significantly (p < 0.05) improved compared to controls, along with a significant (p < 0.05) reduction in terms of retinal microglial activation, and remarkable preservation of RGCs d. Altogether, these findings demonstrated that topical treatment with a P2X7 receptor antagonist has a neuroprotective effect on RGCs in glaucomatous mice, suggesting an appealing pharmacol. approach to prevent retinal degenerative damage in optic neuropathy. The experimental process involved the reaction of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide(cas: 1428327-31-4).Reference of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide

The Article related to p2x7r mutation antagonist retina retinal ganglion glaucoma neuroprotection mouse, gpnm tyrp1 gene mutation p2x7 receptor antagonism glaucoma, glaucoma, p2x7 receptor, perg, retinal ganglion cells and other aspects.Reference of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide

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

On January 5, 2022, Verougstraete, Nick; Stove, Christophe P. published an article.Electric Literature of 380843-75-4 The title of the article was Volumetric absorptive microsampling as a suitable tool to monitor tyrosine kinase inhibitors. And the article contained the following:

Therapeutic drug monitoring (TDM) of tyrosine kinase inhibitors (TKIs) shows significant potential in guiding personalized anticancer treatment. Dried blood microsampling could be a valuable alternative for traditional plasma sampling to provide TDM results faster and to reach a wider audience. Sample collection is easy and patient friendly as only a small volume of blood is collected via a fingerprick. This enables the possibility of home sampling by the patients themselves. Therefore, an LC-MS/MS method was developed and validated for the quantification of bosutinib, dasatinib, gilteritinib, ibrutinib, imatinib, midostaurin, nilotinib and ponatinib in dried blood samples collected via volumetric absorptive microsampling (VAMS). A VAMS device collects a fixed volume of blood (± 10μL), irresp. of the samples hematocrit (Hct). During method validation, special attention was paid to the possible impact of Hct (range 0.18-0.55) on matrix effect (ME), robustness of the extraction, and accuracy of the method. The method was successfully validated based on international guidelines in terms of calibration curves, precision (within-run CV 2.20-14.8%; between-run CV 2.40-12.3%), accuracy (within-run bias 0.34-12.5%; between-run bias -0.15 to 16.2%), carry-over and selectivity. IS-compensated ME and recovery were Hct independent and no significant impact of Hct on the accuracy of the TKI quantifications was observed All TKIs were stable in VAMS samples stored at -20°C, 4°C and room temperature for at least 4 wk and for 2 days at 60°C (except ibrutinib). Lastly, we demonstrated a good agreement between liquid blood obtained from patients on TKI treatment and VAMS samples prepared from that venous blood. As this implies that there is no methodol. impact of liquid vs. dried blood anal., the presented method can be applied in clin. follow-up studies for determining TKIs in (capillary) VAMS samples with varying Hct levels. 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).Electric Literature of 380843-75-4

The Article related to bosutinib dasatinib giitertinib ibrutinib anticancer agent cancer, dried blood microsampling, lc-ms/ms, therapeutic drug monitoring, tyrosine kinase inhibitors, volumetric absorptive microsampling and other aspects.Electric Literature of 380843-75-4

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

On April 30, 2022, Baty, Roua S. published an article.HPLC of Formula: 380843-75-4 The title of the article was Protective effect of Bosutinib with caspase inhibitors on human K562 cells. And the article contained the following:

Cancer therapy has become increasingly focused on molecularly targeted medications. Despite the fact that multi-cytotoxic medication regimens have proven to be highly effective, many investigations in targeted treatments have focused on a single agent. The precise mol. mechanism of action of second-generation BCR-ABL tyrosine kinase inhibitors, which includes different targets and pathways, can help rationalize therapy in chronic myelogenous leukemia (CML) and other diseases affected by BCR-ABL tyrosine kinase inhibitors (TKIs). The purpose of this study was to analyze if bosutinib (BOS) combined with Boc-D-FMK effectively suppressed proliferation and induced apoptosis in K562 cells to a lesser extent, implying that bosutinib is an effective leukemia treatment and that its combination with Boc-D-FMK is a mild chemotherapeutic agent against leukemia. In this study, bosutinib was obtained together with other materials to perform a cell culture experiment with human cell lines, as well as addnl. drug treatment. Furthermore, cell viability (MTT assay) and flow cryometry such as viability and cell cycle assays are performed. The target profile of the dual SRC/ABL inhibitor bosutinib was studied in this study as a first kinase inhibitor to target K562 cells, which has recently been linked to the proliferation of myelogenous leukemia cells, these results suggest the effectiveness of inhibitory activity on cell viability/proliferation, alone generated a potent value of 250 nM (39.27 ± 1.17) for 48 h as optimal dose. The cytotoxic effect of bosutinib on the K562 cell line was assessed in vitro using the MTT assay, and the cytotoxicity was further clarified using cell viability and cell cycle assays. Guava Cell Assay software validated the activation of apoptosis. Sub-G1, G0/G1, S, and G2/M phases are depicted. Cell cycle research revealed that K562 cells treated with bosutinib accumulated much more in the sub-G1 phase, which was later validated by a drop peak at the G2/M phase. In conclusion, the nature of bosutinibs reduction of cancer cell growth may open the door to future research into the development of green synthesis medicines, particularly for cancer treatment. 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).HPLC of Formula: 380843-75-4

The Article related to chronic myelogenous leukemia bosutinib caspase inhibitor apoptosis cancer therapy, apoptosis, boc-d-fmk, bosutinib, cell cycle arrest, cell viability, chronic myelogenous leukaemia (cml), mtt assay and other aspects.HPLC of Formula: 380843-75-4

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

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