Category: piperazines

On March 2, 2021, Biswas, Debabrata; Ambalavanan, Poornima; Ravins, Miriam; Anand, Aparna; Sharma, Abhinay; Lim, Kimberly Xuan Zhen; Tan, Rachel Ying Min; Lim, Hwee Ying; Sol, Asaf; Bachrach, Gilad; Angeli, Veronique; Hanski, Emanuel published an article.Category: piperazines The title of the article was LL-37-mediated activation of host receptors is critical for defense against group A streptococcal infection. And the article contained the following:

Group A Streptococcus (GAS) causes diverse human diseases, including life-threatening soft-tissue infections. It is accepted that the human antimicrobial peptide LL-37 protects the host by killing GAS. Here, we show that GAS extracellular protease ScpC N-terminally cleaves LL-37 into two fragments of 8 and 29 amino acids, preserving its bactericidal activity. At sub-bactericidal concentrations, the cleavage inhibits LL-37-mediated neutrophil chemotaxis, shortens neutrophil lifespan, and eliminates P2X7 and EGF receptors ‘ activation. Mutations at the LL-37 cleavage site protect the peptide from ScpC-mediated splitting, maintaining all its functions. The mouse LL-37 ortholog CRAMP is neither cleaved by ScpC nor does it activate P2X7 or EGF receptors. Treating wild-type or CRAMP-null mice with sub-bactericidal concentrations of the non-cleavable LL-37 analogs promotes GAS clearance that is abolished by the administration of either P2X7 or EGF receptor antagonists. We demonstrate that LL-37-mediated activation of host receptors is critical for defense against GAS soft-tissue infections. 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).Category: piperazines

The Article related to host receptor ll37 activation defense streptococcal infection, cramp, egfr, gas, ll-37, p2x7r, group a streptococcus, host-defense peptides, innate immunity, murine models of human gas soft-tissue infections, neutrophils and other aspects.Category: piperazines

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

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 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

On March 31, 2021, Liu, Juan; Zhang, Yuan; Huang, Honglin; Lei, Xiaoyong; Tang, Guotao; Cao, Xuan; Peng, Junmei published an article.COA of Formula: C26H29Cl2N5O3 The title of the article was Recent advances in Bcr-Abl tyrosine kinase inhibitors for overriding T315I mutation. And the article contained the following:

A review. BCR-ABL is a gene produced by the fusion of the bcr gene and the c-abl proto-oncogene and is considered to be the main cause of chronic myelogenous leukemia (CML) production Therefore, the development of selective Bcr-Abl kinase inhibitors is an attractive strategy for the treatment of CML. However, in the treatment of CML with a Bcr-Abl kinase inhibitor, the T315I gatekeeper mutant disrupts the important contact interaction between the inhibitor and the enzyme, resistant to the first- and second-generation drugs currently approved, such as imatinib, bosutinib, nilotinib, and dasatinib. In order to overcome this special resistance, several different strategies have been explored, and many mols. have been studied to effectively inhibit Bcr-Abl T315I. Some of these mols. are still under development, and some are being studied preclinically, and still others are in clin. research. Herein, this review reports some of the major examples of third-generation Bcr-Abl inhibitors against the T315I mutation. 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).COA of Formula: C26H29Cl2N5O3

The Article related to review imatinib bosutinib anticancer bcr abl chronic myelogenous leukemia, atp-competitive inhibitors, bcr-abl, t315i mutation, chronic myelogenous leukemia, non-atp-competitive inhibitors and other aspects.COA of Formula: C26H29Cl2N5O3

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

On June 30, 2013, Shou, Kai-jun; Li, Jie; Jin, Yi; Lv, Yan-wen published an article.Recommanded Product: 1-Cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid hydrochloride hydrate The title of the article was Design, synthesis, biological evaluation, and molecular docking studies of quinolone derivatives as potential antitumor topoisomerase I inhibitors. And the article contained the following:

A novel series of quinolone derivatives were designed and synthesized, and their biol. activities were evaluated as potential antitumor topoisomerase I (Top I) inhibitors. Among these compounds, one compound exhibited the most potent antitumor activities against multiple cancer cell lines. Docking simulation was performed to insert compound this compound into the crystal structure of DNA-Top I to determine the probable binding model. 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).Recommanded Product: 1-Cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid hydrochloride hydrate

The Article related to phenylsulfonyl carbamidoyl quinolone preparation topoisomerase inhibitor structure activity relationship, topoisomerase phenylsulfonyl carbamidoyl quinolone docking antitumor drug design and other aspects.Recommanded Product: 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 October 31, 2013, Bhattacharya, Anindya; Wang, Qi; Ao, Hong; Shoblock, James R.; Lord, Brian; Aluisio, Leah; Fraser, Ian; Nepomuceno, Diane; Neff, Robert A.; Welty, Natalie; Lovenberg, Timothy W.; Bonaventure, Pascal; Wickenden, Alan D.; Letavic, Michael A. published an article.COA of Formula: C28H32N4O2S The title of the article was Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567. And the article contained the following:

Background and Purpose : An increasing body of evidence suggests that the purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7) in the CNS may play a key role in neuropsychiatry, neurodegeneration and chronic pain. In this study, we characterized JNJ-47965567, a centrally permeable, high-affinity, selective P2X7 antagonist. Exptl. Approach : We have used a combination of in vitro assays (calcium flux, radioligand binding, electrophysiol., IL-1β release) in both recombinant and native systems. Target engagement of JNJ-47965567 was demonstrated by ex vivo receptor binding autoradiog. and in vivo blockade of Bz-ATP induced IL-1β release in the rat brain. Finally, the efficacy of JNJ-47965567 was tested in standard models of depression, mania and neuropathic pain. Key Results : JNJ-47965567 is potent high affinity (pKi 7.9 ± 0.07), selective human P2X7 antagonist, with no significant observed speciation. In native systems, the potency of the compound to attenuate IL-1β release was 6.7 ± 0.07 (human blood), 7.5 ± 0.07 (human monocytes) and 7.1 ± 0.1 (rat microglia). JNJ-47965567 exhibited target engagement in rat brain, with a brain EC50 of 78 ± 19 ng·mL-1 (P2X7 receptor autoradiog.) and functional block of Bz-ATP induced IL-1β release. JNJ-47965567 (30 mg·kg-1) attenuated amphetamine-induced hyperactivity and exhibited modest, yet significant efficacy in the rat model of neuropathic pain. No efficacy was observed in forced swim test. Conclusion and Implications : JNJ-47965567 is centrally permeable, high affinity P2X7 antagonist that can be used to probe the role of central P2X7 in rodent models of CNS pathophysiol. 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).COA of Formula: C28H32N4O2S

The Article related to neuroprotectant jnj47965567 p2x7 receptor antagonist central nervous system, p2x7, autoradiography, depression, interleukin 1β (il-1β), mania, microdialysis, neuropathic pain, purinergic and other aspects.COA of Formula: C28H32N4O2S

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

On February 5, 2022, Degirmencioglu, Ismail; Iren, Kubra; Yalcin, Izzet; Gol, Cem; Durmus, Mahmut published an article.Name: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone The title of the article was Synthesis of axially disubstituted silicon(IV) phthalocyanines and investigation of their photophysical and photochemical properties. And the article contained the following:

In this study, the axially 1-(4-(3-(6-hydroxyhexyl)-3,4-dihydro-2H-benzo[e][1,3]oxazin-6-yl)piperazin-1-yl)ethanone and 1-(4-(3-(2-(2-hydroxyethoxy)ethyl)-3,4-dihydro-2H-benzo[e][1,3]oxazin-6-yl)piperazin-1-yl)ethanone disubstituted silicon(IV) phthalocyanines and their corresponding quaternized derivatives were synthesized for the first time as candidate photosensitizers for photodynamic therapy (PDT) in cancer treatment. The structures of these novel compounds were confirmed by some spectroscopic techniques such as FT-IR, 1H NMR, 13C NMR, UV-Vis, and mass. The axially substitution increased the solubility of the silicon(IV) phthalocyanines. The prepared silicon(IV) phthalocyanines showed great results achieved from photochem. and photophys. investigations in DMSO solution Especially, high singlet oxygen and the fluorescence quantum yield values of the quaternized silicon (IV) phthalocyanines indicates that these compounds have major potential as photosensitizers in PDT. Furthermore, studied silicon(IV) phthalocyanine complexes could be classified as the stable photosensitizer in accordance with photodegradation study results. The fluorescence quenching behavior of these phthalocyanine complexes was also examined using fluorescence quenching method by 1,4-benzoquinone (BQ). The experimental process involved the reaction of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone(cas: 67914-60-7).Name: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone

The Article related to silicon phthalocyanine disubstituted axial preparation photophys photochem property, fluorescence quenching solubility absorbance photolysis silicon phthalocyanine disubstituted axial and other aspects.Name: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone

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

On May 10, 2018, Yu, Le-Mao; Hu, Zhu; Chen, Yu; Ravji, Azhar; Lopez, Sophia; Plescia, Caroline B.; Yu, Qian; Yang, Hui; Abdelmalak, Monica; Saha, Sourav; Agama, Keli; Kiselev, Evgeny; Marchand, Christophe; Pommier, Yves; An, Lin-Kun published an article.COA of Formula: C12H16N2O2 The title of the article was Synthesis and structure-activity relationship of furoquinolinediones as inhibitors of Tyrosyl-DNA phosphodiesterase 2 (TDP2). And the article contained the following:

Tyrosyl-DNA phosphodiesterase 2 (TDP2) is a recently discovered enzyme specifically repairing topoisomerase II (TOP2)-mediated DNA damage. It has been shown that inhibition of TDP2 synergize with TOP2 inhibitors. Herein, we report the discovery of the furoquinolinedione chemotype as a suitable skeleton for the development of selective TDP2 inhibitors. Compound 1 was identified as a TDP2 inhibitor as a result of screening our inhouse compound library for compounds selective for TDP2 vs. TDP1. Further SAR studies provide several selective TDP2 inhibitors at low-micromolar range. The most potent compound 74 shows inhibitory activity with IC50 of 1.9 and 2.1 μM against recombinant TDP2 and TDP2 in whole cell extracts (WCE), resp. The experimental process involved the reaction of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone(cas: 67914-60-7).COA of Formula: C12H16N2O2

The Article related to furoquinoline dione derivative preparation structure tyrosyl dna phosphodiesterase inhibitor, dna repair, furoquinolinedione, inhibitor, topoisomerase, tyrosyl-dna phosphodiesterase and other aspects.COA of Formula: C12H16N2O2

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

On May 31, 2020, Botros, Liza; Pronk, Manon C. A.; Juschten, Jenny; Liddle, John; Morsing, Sofia K. H.; van Buul, Jaap D.; Bates, Robert H.; Tuinman, Pieter R.; van Bezu, Jan S. M.; Huveneers, Stephan; Bogaard, Harm Jan; van Hinsbergh, Victor W. M.; Hordijk, Peter L.; Aman, Jurjan published an article.COA of Formula: C26H29Cl2N5O3 The title of the article was Bosutinib prevents vascular leakage by reducing focal adhesion turnover and reinforcing junctional integrity. And the article contained the following:

Endothelial barrier dysfunction leads to edema and vascular leak, causing high morbidity and mortality. Previously, Abl kinase inhibition has been shown to protect against vascular leak. Using the distinct inhibitory profiles of clin. available Abl kinase inhibitors, we aimed to provide a mechanistic basis for novel treatment strategies against vascular leakage syndromes. We found that the inhibitor bosutinib most potently protected against inflammation-induced endothelial barrier disruption. In vivo, bosutinib prevented lipopolysaccharide (LPS)-induced alveolar protein extravasation in an acute lung injury mice model. Mechanistically, mitogen-activated protein 4 kinase 4 (MAP4K4) was identified as important novel mediator of endothelial permeability, which signaled via ezrin, radixin and moesin proteins to increase turnover of integrin-based focal adhesions. The combined inhibition of MAP4K4 and Abl-related gene (Arg, also known as ABL2) by bosutinib preserved adherens junction integrity and reduced turnover of focal adhesions, which synergistically act to stabilize the endothelial barrier during inflammation. We conclude that MAP4K4 is an important regulator of endothelial barrier integrity, increasing focal adhesion turnover and disruption of cell-cell junctions during inflammation. Because it inhibits both Arg and MAP4K4, use of the clin. available drug bosutinib might form a viable strategy against vascular leakage syndromes. 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).COA of Formula: C26H29Cl2N5O3

The Article related to bosutinib antiinflammatory agent focal adhesion acute lung injury, bosutinib, endothelial barrier function, focal adhesion, map4k4, tyrosine kinase inhibitors, vascular permeability and other aspects.COA of Formula: C26H29Cl2N5O3

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