Month: November 2022

Muresan, Bogdan; Mamolo, Carla; Cappelleri, Joseph C.; Leip, Eric; Viqueira, Andrea; Heeg, Bart published an article in 2021, the title of the article was An indirect comparison between bosutinib, nilotinib and dasatinib in first-line chronic phase chronic myeloid leukemia.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:

Bosutinib, nilotinib and dasatinib are approved for the treatment of patients with newly diagnosed chronic-phase chronic myeloid leukemia (CP-CML). In the absence of head-to-head comparisons between second-generation tyrosine kinase inhibitors (TKIs), the objective of this study was to indirectly compare the efficacy of bosutinib with nilotinib and dasatinib in first-line (1L) CP-CML. Cross-trial heterogeneity in terms of patient baseline characteristics and imatinib dose escalation are difficult to adjust for in network meta-analyses and anchored matching-adjusted indirect treatment comparisons (MAICs). Therefore, an unanchored MAIC was performed using patient level data from bosutinib (BFORE trial) and published aggregated data from nilotinib (ENESTnd) and dasatinib (DASISION) trials. After matching, cytogenetic and mol. responses, and disease progression, after a min. follow-up of 24 mo were compared between nilotinib vs. bosutinb and dasatinib vs. bosutinib. The comparison of nilotinib vs. bosutinib resulted in no statistically significant differences for MMR at and by 24 mo, MR4 by 24 mo, MR4.5 at and by 24 mo, CCyR by 24 mo, and disease progression, however, a decreased odds of MR4 at 24 mo in favor of bosutinib vs. nilotinib was observed The comparison of dasatinib vs. bosutinib by 24 mo resulted in no statistically significant differences for MMR, disease progression, and CCyR, however a decreased odds of MR4.5 in favor of bosutinib vs. dasatinib was observed Overall, in these analyses bosutinib demonstrates equivalent efficacy to nilotinib and dasatinib in the treatment of patients with newly diagnosed CP-CML. 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 nilotinib dasatinib chronic phase myeloid leukemia, chronic myeloid leukemia, bosutinib, dasatinib, first line, nilotinib, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents 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

Lu, Xiaoxiao; Guan, Anqi; Chen, Xi; Xiao, Jian; Xie, Mingxuan; Yang, Baishuang; He, Shuya; You, Shaojin; Li, Wei; Chen, Qiong published an article in 2020, the title of the article was mPRa mediates P4/Org OD02-0 to improve the sensitivity of lung adenocarcinoma to EGFR-TKIs via the EGFR-SRC-ERK1/2 pathway.Synthetic Route of 380843-75-4 And the article contains the following content:

The discovery of epidermal growth factor receptor (EGFR) mutations has made EGFR tyrosine kinase inhibitors (EGFR-TKIs) a milestone in the treatment for advanced non-small cell lung cancer (NSCLC). However, patients lacking EGFR mutations are not sensitive to EGFR-TKI treatment and the emergence of secondary resistance poses new challenges for the targeted therapy of lung cancer. In this study, we identified that the expression of membrane progesterone receptor a (mPRa) was associated with EGFR mutations in lung adenocarcinoma patients and subsequently affected the efficacy of EGFR-TKIs. Progesterone (P4) or its derivative Org OD02-0 (Org), which is mediated by mPRa, increases the function of EGFR-TKIs to suppress the proliferation, migration, and invasion of lung adenocarcinoma cells in vitro and in vivo. In addition, the mPRa pathway triggers delayed resistance to EGFR-TKIs. Mechanistic investigations demonstrated that the mPRa pathway can crosstalk with the EGFR pathway by activating nongenomic effects to inhibit the EGFR-SRC-ERK1/2 pathway, thereby promoting antitumorigenic effects. In conclusion, our data describe an essential role for mPRa in improving sensitivity to EGFR-TKIs, thus rationalizing its potential as a therapeutic target for lung adenocarcinomas. 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).Synthetic Route of 380843-75-4

The Article related to lung adenocarcinoma membrane progesterone receptor a egfr mutation, egfr mutations, egfr-tkis, lung adenocarcinoma, mprα, sensitivity, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Synthetic Route of 380843-75-4

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

On December 9, 2021, Perfettini, Jean-Luc; Lecuyer, Deborah; Tannous, Desiree; Allouch, Awatef; Delelis, Olivier; Subra, Frederic published a patent.Quality Control of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide The title of the patent was Modulators of purinergic receptors and related immune checkpoint for treating acute respiratory distress syndrome. And the patent contained the following:

The inventors herein show that purinergic receptors regulate the conversion of macrophage pro-inflammatory reprogramming into anti-inflammatory phenotype in patients suffering from COVID-19 disease. Moreover, they show that P2Y receptor agonists repress NLRP3 inflammasome-dependent IL-1b secretion, but also impair the replication and the cytopathogenic effects of SARS-CoV-2. These results therefore suggest that some purinergic receptors agonists can treat acute lung injury and respiratory disease that are associated with SARS-CoV-2 infection. In addition, their results show that antagonists of the purinergic receptors P2X impair the replication of said virus. The present invention therefore proposes to use purinergic receptors modulators and NLR3-P2Y2R immune checkpoint modulators to treat patients suffering from a virus-induced acute respiratory distress syndrome. 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).Quality Control of N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide

The Article related to purinergic receptors modulators sars cov2 covid19 respiratory system disease, Pharmacology: Effects Of Gastrointestinal and Respiratory Drugs and other aspects.Quality Control 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 August 1, 2017, Shan, Wei-Guang; Wang, Han-Guang; Chen, Yan; Wu, Rui; Wen, Yan-Tao; Zhang, Li-Wen; Ying, You-Min; Wang, Jian-Wei; Zhan, Zha-Jun published an article.Recommanded Product: 4-Ethyl-piperazine-1-carbonyl chloride The title of the article was Synthesis of 3- and 29-substituted celastrol derivatives and structure-activity relationship studies of their cytotoxic activities. And the article contained the following:

A series of 3-carbamate and 29-ester celastrol derivatives I (R1 = H, R2 = H, Me, Et, CHMe2, CH2CH:CH2, CH2Ph, 3-ClC6H4CH2, etc.; R1 = CONMePh, piperidinocarbonyl, morpholinocarbonyl, etc.) were designed and synthesized. These analogs were evaluated for their cytotoxic activities against several cancer cell lines. Cytotoxicity data revealed that the properties of substituents and substitution position had important influence on cytotoxic activity. Modification of C-3 hydroxyl with size-limited groups did not reduce the activity obviously. The introduction of polarity group like piperazine could improve the solubility Compound I (R1 = 4-piperazinocarbonyl, R2 = CH2Ph) (II) was chosen to further evaluate anti-tumor efficacy in vivo. It showed higher inhibition rate and better safety than celastrol during in vivo experiment by intragastric administration. The preliminary antitumor studies of compound II in vivo showed that it might be promising for the development of new antitumor agents. The experimental process involved the reaction of 4-Ethyl-piperazine-1-carbonyl chloride(cas: 53788-12-8).Recommanded Product: 4-Ethyl-piperazine-1-carbonyl chloride

The Article related to celastrol derivative preparation antitumor structure activity, c-3 hydroxyl derivatives, celastrol, cytotoxicity, in vivo activity, intragastric administration, Terpenes and Terpenoids: Triterpenes (C30), Including Limonoids and other aspects.Recommanded Product: 4-Ethyl-piperazine-1-carbonyl chloride

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

On March 21, 1990, Kishimoto, Shoji; Fujita, Takeshi published a patent.Quality Control of 4-Ethyl-piperazine-1-carbonyl chloride The title of the patent was Preparation of O-acylfumagillol derivatives as angiogenesis inhibitors. And the patent contained the following:

The title compounds [I; R1 = CH:CMe2, (un)substituted CH2CHMe2; R2 = substituted alkanoyl, aroyl, (un)substituted heterocyclylcarbonyl, CONH2, alkyl, etc.] were prepared, e.g., by acylation of I (R2 = H). Thus, fumagillol was stirred 20 h with diglycolic anhydride in pyridine to give I (R1 = COCH2OCH2CO2H, R2 = CH:CMe2) which reduced bovine fibroblast growth factor-induced angiogenesis in cornea of 8 of 8 rats evaluated after 7 days. The experimental process involved the reaction of 4-Ethyl-piperazine-1-carbonyl chloride(cas: 53788-12-8).Quality Control of 4-Ethyl-piperazine-1-carbonyl chloride

The Article related to fumagillol substituted preparation angiogenesis inhibitor, Terpenes and Terpenoids: Sesquiterpenes (C15), Including Ionones and other aspects.Quality Control of 4-Ethyl-piperazine-1-carbonyl chloride

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

On March 7, 1990, Kishimoto, Shoji; Fujita, Takeshi; Kanamaru, Tsuneo; Folkman, Moses Judah; Ingber, Donald published a patent.COA of Formula: C7H13ClN2O The title of the patent was Preparation of O-acylfumagillols and analogs as angiogenesis inhibitors. And the patent contained the following:

The title compounds [I; R1 = (un)substituted CH:CMe2, CH2CHMe2; R2 = substituted alkanoyl, aroyl, (un)substituted heteroarylcarbonyl, CONH2, alkyl, PhSO2, alkylsulfonyl, H2NSO2, alkoxycarbonyl, PhO2C] were prepared Thus, fumagillol was stirred 2 h at 0° with ClCH2CONCO in CH2Cl2 containing dimethylaminopyridine to give I (R1 = CH:CMe2, R2 = CONHCOCH2Cl) which suppressed B16 mouse melanoma tumor growth to 20% that of controls after 3 wk in mice receiving 30 mg/kg s.c. every other day. The experimental process involved the reaction of 4-Ethyl-piperazine-1-carbonyl chloride(cas: 53788-12-8).COA of Formula: C7H13ClN2O

The Article related to acylfumagillol preparation angiogenesis inhibitor, fumagillol acyl preparation angiogenesis inhibitor, Terpenes and Terpenoids: Sesquiterpenes (C15), Including Ionones and other aspects.COA of Formula: C7H13ClN2O

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

On August 31, 2021, Lakkireddy, Samyuktha; Jayaraman, Archana; Aula, Sangeetha; Kapley, Atya; Kutala, Vijay Kumar; Jamil, Kaiser published an article.Reference 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 In Silico Docking Studies of Vascular Endothelial Growth Factor-A (VEGFA): Possible Implications in Chronic Myeloid Leukemia (CML) Therapy. And the article contained the following:

Background: Dysregulated angiogenesis resulting in neovascularization is a critical event in the expansion and progression of Chronic Myeloid Leukemia (CML), hematopoietic cancer. Vascular Endothelial Growth Factor- A (VEGFA), an important angiogenesis mediator, has been a target for treating cancer. Although several anti-VEGFA drugs are available, they are associated with adverse side effects, promoting the need to identify better drugs that may be less toxic. Objective: Our aim was to investigate whether Tyrosine Kinase Inhibitors (TKIs) could be repurposed for use as VEGFA inhibitors via in silico docking software. We also investigated the potential of phytochems. as VEGFA inhibitors. Methods: We performed mol. docking using Schrodinger Maestro software suite 2014-3 to determine the most potent phytochem. and TKI VEGFA antagonists. Results: Among the TKIs investigated, Bosutinib had the best binding affinity and may be the most potent TKI against VEGFA. The order of binding affinities for the top ten docked ligands was: Ginsenoside Rg3> Bosutinib> Vitamin D> Paclitaxel> Dasatinib> Saponins> Ponatinib> Squalamine> Imatinib> Nilotinib. We found that Ginsenoside Rg3 had the highest binding affinity (MMGBSA score= -99.4 kcal/mol, glide Gscore = -9.16 kcal/mol) to VEGFA. Conclusion: Our study has shown for the first time the binding poses of these TKIs and phytochems. to VEGFA, using computational methods. We propose that the use of the top scoring ligands, in isolation or a combination of phytochems. plus TKI, could serve as potent angiogenesis inhibitors via their binding to and inhibiting VEGFA expression to prevent CML progression. We have also profiled the ligand binding residues, which may be explored in designing pharmacophores. 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).Reference of 4-((2,4-Dichloro-5-methoxyphenyl)amino)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinoline-3-carbonitrile

The Article related to chronic myeloid leukemia docking vegfa, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Reference 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 November 25, 2021, Rea, Delphine; Mauro, Michael J.; Boquimpani, Carla; Minami, Yosuke; Lomaia, Elza; Voloshin, Sergey; Turkina, Anna; Kim, Dong-Wook; Apperley, Jane F.; Abdo, Andre; Fogliatto, Laura Maria; Kim, Dennis Dong Hwan; le Coutre, Philipp; Saussele, Susanne; Annunziata, Mario; Hughes, Timothy P.; Chaudhri, Naeem; Sasaki, Koji; Chee, Lynette; Garcia-Gutierrez, Valentin; Cortes, Jorge E.; Aimone, Paola; Allepuz, Alex; Quenet, Sara; Bedoucha, Veronique; Hochhaus, Andreas published an article.SDS of cas: 380843-75-4 The title of the article was A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. And the article contained the following:

Patients with chronic myeloid leukemia in chronic phase (CML-CP) resistant/intolerant to ≥2 tyrosine kinase inhibitors (TKIs) are at high risk of experiencing poor outcomes because of disease biol. and inadequate efficacy and/or safety of current therapies. Asciminib, a first-in-class BCR-ABL1 inhibitor Specifically Targeting the ABL Myristoyl Pocket (STAMP), has the potential to overcome resistance/intolerance to approved TKIs. In this phase 3, open-label study, patients with CML-CP previously treated with ≥2 TKIs were randomized (2:1) to receive asciminib 40 mg twice daily vs bosutinib 500 mg once daily. Randomization was stratified by major cytogenetic response (MCyR) status at baseline. The primary objective was to compare the major mol. response (MMR) rate at week 24 for asciminib vs bosutinib. A total of 233 patients were randomized to asciminib (n = 157) or bosutinib (n = 76). Median follow-up was 14.9 mo. The MMR rate at week 24 was 25.5% with asciminib and 13.2% with bosutinib. The difference in MMR rate between treatment arms, after adjusting for MCyR at baseline, was 12.2% (95% confidence interval, 2.19-22.30; 2-sided P = .029). Fewer grade ≥3 adverse events (50.6% vs 60.5%) and adverse events leading to treatment discontinuation (5.8% vs 21.1%) occurred with asciminib than with bosutinib. The study showed a superior efficacy of asciminib compared with that of bosutinib, together with a favorable safety profile. These results support the use of asciminib as a new therapy in patients with CML-CP who are resistant/intolerant to ≥2 prior TKIs. This trial was registered at www.clinicaltrials.gov as #NCT03106779. 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).SDS of cas: 380843-75-4

The Article related to bosutinib anticancer agent chronic myeloid leukemia, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.SDS of cas: 380843-75-4

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

Cayssials, Emilie; Torregrosa-Diaz, Jose; Leleu, Xavier; Guilhot, Francois; Chomel, Jean-Claude published an article in 2021, the title of the article was Reply to Comment on low-dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment-free remission in chronic myeloid leukemia patients: Results of a retrospective study.SDS of cas: 380843-75-4 And the article contains the following content:

The present invention relates to a retrospective study on reply to comment on low-dose tyrosine kinase inhibitors before treatment discontinuation do not impair treatment-free remission in chronic myeloid leukemia patients. 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).SDS of cas: 380843-75-4

The Article related to tyrosine kinase inhibitor chronic myeloid leukemia human, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.SDS of cas: 380843-75-4

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

Abaza, Yasmin; Kantarjian, Hagop; Alwash, Yasmin; Borthakur, Gautam; Champlin, Richard; Kadia, Tapan; Garcia-Manero, Guillermo; Daver, Naval; Ravandi, Farhad; Verstovsek, Srdan; Burger, Jan; Estrov, Zeev; Ohanian, Maro; Lim, Miranda; Pemmaraju, Naveen; Jabbour, Elias; Cortes, Jorge published an article in 2020, the title of the article was Phase I/II study of dasatinib in combination with decitabine in patients with accelerated or blast phase chronic myeloid leukemia.Application In Synthesis of 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:

Treatment of advanced-phase chronic myeloid leukemia (CML) remains unsatisfactory. Single-agent tyrosine kinase inhibitors have modest and short-lived activity in this setting. We conducted a phase I/II study to determine safety and efficacy of the combination of dasatinib and decitabine in patients with advanced CML. Two different dose schedules were investigated with a starting decitabine dose of either 10 mg/m2 or 20 mg/m2 daily for 10 days plus dasatinib 100 mg daily. The target dose level was decitabine 10 mg/m2 or 20 mg/m2 daily for 10 days plus dasatinib 140 mg daily. Thirty patients were enrolled, including seven with accelerated-phase CML, 19 with blast-phase CML, and four with Philadelphia-chromosome pos. acute myeloid leukemia. No dose-limiting toxicity was observed at the starting dose level with either schedule. Grade ≥3 treatment emergent hematol. adverse events were reported in 28 patients. Thirteen patients (48%) achieved a major hematol. response and six (22%) achieved a minor hematol. response, with 44% of these patients achieving a major cytogenetic response and 33% achieving a major mol. response. Median overall survival (OS) was 13.8 mo, with significantly higher OS among patients who achieved a hematol. response compared to non-responders (not reached vs 4.65 mo; P < .001). Decitabine plus dasatinib is a safe and active regimen in advanced CML. Further studies using this combination are warranted. 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 dasatinib decitabine anticancer agent chronic myeloid leukemia, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents 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