Tag: 400-500

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 May 1, 2018, Fan, Jianjia; Zhao, Rui Qi; Parro, Cameron; Zhao, Wenchen; Chou, Hsien-Ya; Robert, Jerome; Deeb, Tarek Z.; Raynoschek, Carina; Barichievy, Samantha; Engkvist, Ola; Maresca, Marcello; Hicks, Ryan; Meuller, Johan; Moss, Stephen J.; Brandon, Nicholas J.; Wood, Michael W.; Kulic, Iva; Wellington, Cheryl L. published an article.Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide The title of the article was Small molecule inducers of ABCA1 and apoE that act through indirect activation of the LXR pathway. And the article contained the following:

ApoE is the primary lipid carrier within the CNS and the strongest genetic risk factor for late onset Alzheimer’s disease (AD). apoE is primarily lipidated via ABCA1, and both are under transcriptional regulation by the nuclear liver X receptor (LXR). Considerable evidence from genetic (using ABCA1 overexpression) and pharmacol. (using synthetic LXR agonists) studies in AD mouse models suggests that increased levels of lipidated apoE can improve cognitive performance and, in some strains, can reduce amyloid burden. However, direct synthetic LXR ligands have hepatotoxic side effects that limit their clin. use. Here, we describe a set of small mols., previously annotated as antagonists of the purinergic receptor, P2X7, which enhance ABCA1 expression and activity as well as apoE secretion, and are not direct LXR ligands. Furthermore, P2X7 is not required for these mols. to induce ABCA1 upregulation and apoE secretion, demonstrating that the ABCA1 and apoE effects are mechanistically independent of P2X7 inhibition. Hence, we have identified novel dual activity compounds that upregulate ABCA1 across multiple CNS cell types, including human astrocytes, pericytes, and microglia, through an indirect LXR mechanism and that also independently inhibit P2X7 receptor activity. 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).Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide

The Article related to astrocytoma hepatoma cell abca1 apoe lxr, alzheimer’s disease, p2x7 receptor, adenosine 5′-triphosphate-binding cassette transporter a1, apolipoprotein e, astrocyte, brain, nuclear receptors/liver x receptor and other aspects.Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide

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

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 April 20, 2016, Ziff, Jeannie; Rudolph, Dale A.; Stenne, Brice; Koudriakova, Tatiana; Lord, Brian; Bonaventure, Pascal; Lovenberg, Timothy W.; Carruthers, Nicholas I.; Bhattacharya, Anindya; Letavic, Michael A.; Shireman, Brock T. published an article.COA of Formula: C28H32N4O2S The title of the article was Substituted 5,6-(Dihydropyrido[3,4-d]pyrimidin-7(8H)-yl)-methanones as P2X7 Antagonists. And the article contained the following:

We describe the synthesis of a novel class of brain penetrating P2X7 antagonists with high potency at both the rat and human P2X7 receptors. Disclosed herein are druglike mols. with demonstrated target engagement of the rat P2X7 receptors after an oral dose. Specifically, compound 20 occupied the P2X7 receptors >80% over the 6 h time course as measured by an ex vivo radioligand binding experiment In a dose-response assay, this mol. has a plasma EC50 of 8 ng/mL. Overall, 20 has suitable druglike properties and pharmacokinetics in rat and dog. This mol. and others disclosed herein will serve as addnl. tools to elucidate the role of the P2X7 receptor in neuropsychiatric disorders. 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 dihydropyrido pyrimidinyl methanone derivative preparation p2x7 antagonist, 5,6-dihydropyrido[3,4-d]pyrimidin-7(8h)-yl) methanones, cns, il-1β, p2x7, depression, neuroinflammation and other aspects.COA of Formula: C28H32N4O2S

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 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 March 31, 2020, Ly, Diane; Dongol, Anjila; Cuthbertson, Peter; Guy, Thomas V.; Geraghty, Nicholas J.; Sophocleous, Reece A.; Sin, Lucia; Turner, Bradley J.; Watson, Debbie; Yerbury, Justin J.; Sluyter, Ronald published an article.Application of 1428327-31-4 The title of the article was The P2X7 receptor antagonist JNJ-47965567 administered thrice weekly from disease onset does not alter progression of amyotrophic lateral sclerosis in SOD1G93A mice.. And the article contained the following:

Abstract: The ATP-gated P2X7 ion channel has emerging roles in amyotrophic lateral sclerosis (ALS) progression. Therefore, the current study aimed to determine whether the CNS-penetrant P2X7 antagonist, JNJ-47965567, could ameliorate ALS progression in SOD1G93A mice. A flow cytometric assay revealed that JNJ-47965567 impaired ATP-induced cation dye uptake in a concentration-dependent manner in murine J774 macrophages. Female and male SOD1G93A mice were injected i.p. with JNJ-47965567 (30 mg/kg) or 2-(hydroxypropyl)-beta-cyclodextrin (vehicle control) three times a week from disease onset until end stage, when tissues were collected and studied. JNJ-47965567 did not impact weight loss, clin. score, motor (rotarod) coordination or survival compared to control mice. NanoString anal. revealed altered spinal cord gene expression in JNJ-47965567 mice compared to control mice, but such differences were not confirmed by quant. PCR. Flow cytometric analyses revealed no differences between treatments in the frequencies or activation status of T cell or dendritic cell subsets in lymphoid tissues or in the concentrations of serum cytokines. Notably, serum IL-27, IFNbetaand IL-10 were present in relatively high concentrations compared to other cytokines in both groups. In conclusion, JNJ-47965567 administered thrice weekly from disease onset did not alter disease progression or mol. and cellular parameters in SOD1G93A mice. 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 amyotrophic lateral sclerosis p2x7 receptor antagonist jnj47965567, amyotrophic lateral sclerosis, motor neurone disease, nqo1, p2x7 receptor, purinergic receptor, sod1g93a mice and other aspects.Application of 1428327-31-4

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 May 1, 2018, Fan, Jianjia; Zhao, Rui Qi; Parro, Cameron; Zhao, Wenchen; Chou, Hsien-Ya; Robert, Jerome; Deeb, Tarek Z.; Raynoschek, Carina; Barichievy, Samantha; Engkvist, Ola; Maresca, Marcello; Hicks, Ryan; Meuller, Johan; Moss, Stephen J.; Brandon, Nicholas J.; Wood, Michael W.; Kulic, Iva; Wellington, Cheryl L. published an article.Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide The title of the article was Small molecule inducers of ABCA1 and apoE that act through indirect activation of the LXR pathway. And the article contained the following:

ApoE is the primary lipid carrier within the CNS and the strongest genetic risk factor for late onset Alzheimer’s disease (AD). apoE is primarily lipidated via ABCA1, and both are under transcriptional regulation by the nuclear liver X receptor (LXR). Considerable evidence from genetic (using ABCA1 overexpression) and pharmacol. (using synthetic LXR agonists) studies in AD mouse models suggests that increased levels of lipidated apoE can improve cognitive performance and, in some strains, can reduce amyloid burden. However, direct synthetic LXR ligands have hepatotoxic side effects that limit their clin. use. Here, we describe a set of small mols., previously annotated as antagonists of the purinergic receptor, P2X7, which enhance ABCA1 expression and activity as well as apoE secretion, and are not direct LXR ligands. Furthermore, P2X7 is not required for these mols. to induce ABCA1 upregulation and apoE secretion, demonstrating that the ABCA1 and apoE effects are mechanistically independent of P2X7 inhibition. Hence, we have identified novel dual activity compounds that upregulate ABCA1 across multiple CNS cell types, including human astrocytes, pericytes, and microglia, through an indirect LXR mechanism and that also independently inhibit P2X7 receptor activity. 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).Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide

The Article related to astrocytoma hepatoma cell abca1 apoe lxr, alzheimer’s disease, p2x7 receptor, adenosine 5′-triphosphate-binding cassette transporter a1, apolipoprotein e, astrocyte, brain, nuclear receptors/liver x receptor and other aspects.Recommanded Product: N-((4-(4-Phenylpiperazin-1-yl)tetrahydro-2H-pyran-4-yl)methyl)-2-(phenylthio)nicotinamide

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

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