Month: November 2022

On April 30, 2020, Daerr, Markus; Allmendinger, Lars; Hoefner, Georg; Wanner, Klaus T. published an article.Synthetic Route of 39512-49-7 The title of the article was Synthesis and biological evaluation of fluorescent GAT-ligands based on asymmetric substituted BODIPY dyes. And the article contained the following:

The present study aimed at the development of fluorescent inhibitors addressing the GABA transporters mGAT1-mGAT4 as potential tool compounds in fluorescence based biol. assays. The design of these fluorescent GAT inhibitors followed the structural motifs common for many GAT1-GAT4 inhibitors publicly known except that the lipophilic domain present in this compounds was replaced by a BODIPY moiety to serve as a fluorescent subunit. The fluorescent compounds obtained that way were tested for their inhibitory potencies and subtype selectivities at the four murine GABA transporter subtypes mGAT1-mGAT4 and for their binding affinity for mGAT1. All BODIPY derivatives displayed only low inhibitory potencies and subtype selectivities at the GABA transport proteins mGAT1-mGAT4, as well as low affinities for mGAT1. Still, compounds were found with reasonable binding affinities towards mGAT1 (pKi ∼ 5.0) and inhibitory potencies at mGAT2 and mGAT4 (pIC50 ∼ 5.0). The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Synthetic Route of 39512-49-7

The Article related to fluorescent gat ligand asymmetry bodipy dye, Pharmacology: Structure-Activity and other aspects.Synthetic Route of 39512-49-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On November 14, 2019, Fyfe, Tim J.; Kellam, Barrie; Sykes, David A.; Capuano, Ben; Scammells, Peter J.; Lane, J. Robert; Charlton, Steven J.; Mistry, Shailesh N. published an article.Quality Control of 4-(4-Chlorophenyl)piperidin-4-ol The title of the article was Structure-Kinetic Profiling of Haloperidol Analogues at the Human Dopamine D2 Receptor. And the article contained the following:

Haloperidol is a typical antipsychotic drug (APD) associated with an increased risk of extrapyramidal side-effects (EPS) and hyperprolactinemia relative to atypical APDs such as clozapine. Both drugs are dopamine D2 receptor (D2R) antagonists, with contrasting kinetic profiles. Haloperidol displays fast association/slow dissociation at the D2R whereas clozapine exhibits relatively slow association/fast dissociation Recently, the authors have provided evidence that slow dissociation from the D2R predicts hyperprolactinemia, whereas fast association predicts EPS. Unfortunately, clozapine can cause severe side-effects independent of its D2R action. The results suggest an optimal kinetic profile for D2R antagonist APDs that avoids EPS. To begin exploring this hypothesis, the authors conducted a structure-kinetic relationship study of haloperidol and reveal that subtle structural modifications dramatically change binding kinetic rate constants, affording compounds with a clozapine-like kinetic profile. Thus, optimization of these kinetic parameters may allow development of novel APDs based on the haloperidol scaffold with improved side-effect profiles. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Quality Control of 4-(4-Chlorophenyl)piperidin-4-ol

The Article related to structure pharmacokinetics haloperidol dopamine d2 receptor, Pharmacology: Structure-Activity and other aspects.Quality Control of 4-(4-Chlorophenyl)piperidin-4-ol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On November 15, 2009, Burgey, Christopher S.; Potteiger, Craig M.; Deng, James Z.; Mosser, Scott D.; Salvatore, Christopher A.; Yu, Sean; Roller, Shane; Kane, Stefanie A.; Vacca, Joseph P.; Williams, Theresa M. published an article.Formula: C19H18ClN3O4 The title of the article was Optimization of azepanone calcitonin gene-related peptide (CGRP) receptor antagonists: Development of novel spiropiperidines. And the article contained the following:

Several novel spiropiperidine-based CGRP receptor antagonists have been developed that maintain good potency and have reduced potential for metabolism The experimental process involved the reaction of Benzyl 7′-chloro-2′-oxo-1′,2′-dihydrospiro[piperidine-4,4′-pyrido[2,3-d][1,3]oxazine]-1-carboxylate(cas: 883984-95-0).Formula: C19H18ClN3O4

The Article related to spiropiperidine cgrp receptor antagonist preparation migraine, Pharmacology: Structure-Activity and other aspects.Formula: C19H18ClN3O4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Yue, Liyan; Du, Juanjuan; Ye, Fei; Chen, Zhifeng; Li, Lianchun; Lian, Fulin; Zhang, Bidong; Zhang, Yuanyuan; Jiang, Hualiang; Chen, Kaixian; Li, Yuanchao; Zhou, Bing; Zhang, Naixia; Yang, Yaxi; Luo, Cheng published an article in 2016, the title of the article was Identification of novel small-molecule inhibitors targeting menin-MLL interaction, repurposing the antidiarrheal loperamide.Reference of 4-(4-Chlorophenyl)piperidin-4-ol And the article contains the following content:

Leukemia with a mixed lineage leukemia (MLL) rearrangement, which harbors a variety of MLL fusion proteins, has a poor prognosis despite the latest improved treatment options. Menin has been reported to be a required cofactor for the leukemogenic activity of MLL fusion proteins. Thus, the disruption of the protein-protein interactions between menin and MLL represents a very promising strategy for curing MLL leukemia. Making use of menin-MLL inhibitors with a shape-based scaffold hopping approach, the authors have discovered that the antidiarrheal loperamide displays previously unreported mild inhibition for the menin-MLL interaction (IC50 = 69±3 μM). In an effort to repurpose this drug, a series of chem. modification analyses was performed, and three of the loperamide-based analogs, DC_YM21, DC_YM25 and DC_YM26 displayed better activities with IC50 values of 0.83±0.13 μM, 0.69±0.07 μM and 0.66±0.05 μM, resp. Further treatment with DC_YM21 demonstrated potent and selective blockage of proliferation and induction of both cell cycle arrest and differentiation of leukemia cells harboring MLL translocations, which confirmed the specific mechanism of action. In conclusion, mols. of a novel scaffold targeting menin-MLL interactions were reported and they may serve as new potential therapeutic agents for MLL leukemia. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Reference of 4-(4-Chlorophenyl)piperidin-4-ol

The Article related to menin mll inhibitor interaction loperamide antitumor leukemia, Pharmacology: Structure-Activity and other aspects.Reference of 4-(4-Chlorophenyl)piperidin-4-ol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On November 11, 2021, Bricelj, Alesa; Dora Ng, Yuen Lam; Ferber, Dominic; Kuchta, Robert; Muller, Sina; Monschke, Marius; Wagner, Karl G.; Kronke, Jan; Sosic, Izidor; Gutschow, Michael; Steinebach, Christian published an article.Category: piperidines The title of the article was Influence of Linker Attachment Points on the Stability and Neosubstrate Degradation of Cereblon Ligands. And the article contained the following:

Proteolysis targeting chimeras (PROTACs) hijacking the cereblon (CRBN) E3 ubiquitin ligase have emerged as a novel paradigm in drug development. Herein we found that linker attachment points of CRBN ligands highly affect their aqueous stability and neosubstrate degradation features. This work provides a blueprint for the assembly of future heterodimeric CRBN-based degraders with tailored properties. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Category: piperidines

The Article related to protac crbn stability neosubstrate cereblon linker degradation, Pharmacology: Structure-Activity and other aspects.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On January 15, 2010, Stewart, Scott G.; Braun, Carlos J.; Ng, Sze-Ling; Polomska, Marta E.; Karimi, Mahdad; Abraham, Lawrence J. published an article.Electric Literature of 1216805-11-6 The title of the article was New thalidomide analogues derived through Sonogashira or Suzuki reactions and their TNF expression inhibition profiles. And the article contained the following:

A library of new thalidomide C4/5 analogs containing either a Ph or alkyne tether were synthesized using Sonogashira or Suzuki cross coupling reactions from their aryl halogenated precursors. All thalidomide analogs were tested for their ability to inhibit the expression of the proinflammatory cytokine Tumor Necrosis Factor (TNF). More explicitly the use of a novel reporter system utilizing the promoter region of the TNF gene in a human T-cell line provided a rapid and effective measure of NFκB transcriptional activity. Several compounds either containing either an aryl-iso-Bu or aryl-isopropoxy group were the most effective in inhibiting TNF expression, and were several times more active than thalidomide itself. Five of the more active derivatives indicated an apoptotic response while one of these compounds, containing an aldehyde tether, showed possible influence of cell cycling effects. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Electric Literature of 1216805-11-6

The Article related to structure thalidomide analog preparation tnf inhibition cancer, Pharmacology: Structure-Activity and other aspects.Electric Literature of 1216805-11-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On June 12, 2014, Szabo, Monika; Klein Herenbrink, Carmen; Christopoulos, Arthur; Lane, J. Robert; Capuano, Ben published an article.Computed Properties of 39512-49-7 The title of the article was Structure-Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D2 Receptor. And the article contained the following:

Biased agonism at GPCRs highlights the potential for the discovery and design of pathway-selective ligands and may confer therapeutic advantages to ligands targeting the dopamine D2 receptor (D2R). We investigated the determinants of efficacy, affinity, and bias for three privileged structures for the D2R, exploring changes to linker length and incorporation of a heterocyclic unit. Profiling the compounds in two signaling assays (cAMP and pERK1/2) allowed us to identify and quantify determinants of biased agonism at the D2R. Substitution on the phenylpiperazine privileged structures (2-methoxy vs 2,3-dichloro) influenced bias when the thienopyridine heterocycle was absent. Upon inclusion of the thienopyridine unit, the substitution pattern (4,6-di-Me vs 5-chloro-6-methoxy-4-methyl) had a significant effect on bias that overruled the effect of the phenylpiperazine substitution pattern. This latter observation could be reconciled with an extended binding mode for these compounds, whereby the interaction of the heterocycle with a secondary binding pocket may engender bias. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Computed Properties of 39512-49-7

The Article related to methoxyphenylpiperazine linker d2 receptor ligand preparation sar, Pharmacology: Structure-Activity and other aspects.Computed Properties of 39512-49-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On November 26, 2012, Cavallaro, Cullen L.; Briceno, Stephanie; Chen, Jing; Cvijic, Mary Ellen; Davies, Paul; Hynes, John; Liu, Rui-Qin; Mandlekar, Sandhya; Rose, Anne V.; Tebben, Andrew J.; Van Kirk, Katy; Watson, Andrew; Wu, Hong; Yang, Guchen; Carter, Percy H. published an article.Computed Properties of 39512-49-7 The title of the article was Discovery and Lead Optimization of a Novel Series of CC Chemokine Receptor 1 (CCR1)-Selective Piperidine Antagonists via Parallel Synthesis. And the article contained the following:

A series of novel, potent CCR1 inhibitors was developed from a moderately active hit using an iterative parallel synthesis approach. The initial hit (composed of three subunits: an amine, a central amino acid, and an N-terminal cap) became the basis for a series of parallel chem. libraries designed to generate SAR data. Libraries were synthesized that explored each of the three subunits; the CCR1 binding data obtained revealed the following: changes to the amine are not well tolerated; small alkylamino acids are preferred in the center of the mol.; substitutions at the N-terminus are generally well tolerated. These data were used to drive the optimization of the series, ultimately providing a lead with a CCR1 binding IC50 of 28 nM (48). This lead demonstrates high selectivity for CCR1 over other CCR-family members, high microsomal stability, and good pharmacokinetics in mice. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Computed Properties of 39512-49-7

The Article related to structure activity preparation chemokine receptor ccr1 antagonist, Pharmacology: Structure-Activity and other aspects.Computed Properties of 39512-49-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On May 15, 2006, Gilmore, John L.; King, Bryan W.; Harris, Cathy; Maduskuie, Thomas; Mercer, Stephen E.; Liu, Rui-Qin; Covington, Maryanne B.; Qian, Mingxin; Ribadeneria, Maria D.; Vaddi, Krishna; Trzaskos, James M.; Newton, Robert C.; Decicco, Carl P.; Duan, James J.-W. published an article.Safety of tert-Butyl 4-amino-4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate The title of the article was Synthesis and structure-activity relationship of a novel, achiral series of TNF-α converting enzyme inhibitors. And the article contained the following:

A novel series of achiral TNF-α converting enzyme (TACE) inhibitors has been discovered. These compounds exhibited activities from 0.35 to 11 nM in a porcine TACE assay and inhibited TNF-α production in an LPS-stimulated whole blood assay with an IC50 value of 23 nM for the most potent one. They also have excellent selectivities over related metalloproteases including aggrecanases. The experimental process involved the reaction of tert-Butyl 4-amino-4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate(cas: 362703-57-9).Safety of tert-Butyl 4-amino-4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate

The Article related to metalloprotease preparation sar tnf tumor necrosis factor inhibitor, Pharmacology: Structure-Activity and other aspects.Safety of tert-Butyl 4-amino-4-(2-methoxy-2-oxoethyl)piperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On April 20, 2018, Amato, Anastasia; Lucas, Xavier; Bortoluzzi, Alessio; Wright, David; Ciulli, Alessio published an article.Safety of 4-(4-Chlorophenyl)piperidin-4-ol The title of the article was Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach. And the article contained the following:

Plant homeodomain (PHD) zinc fingers are histone reader domains that are often associated with human diseases. Despite this, they constitute a poorly targeted class of readers, suggesting low ligandability. Here, the authors describe a successful fragment-based campaign targeting PHD fingers from the proteins BAZ2A and BAZ2B as model systems. The authors validated a pool of in silico fragments both biophys. and structurally and solved the first crystal structures of PHD zinc fingers in complex with fragments bound to an anchoring pocket at the histone binding site. The best-validated hits displace a histone H3 tail peptide in competition assays. This work identifies new chem. scaffolds that provide suitable starting points for future ligand optimization using structure-guided approaches. The demonstrated ligandability of the PHD reader domains could pave the way for the development of chem. probes to drug this family of epigenetic readers. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Safety of 4-(4-Chlorophenyl)piperidin-4-ol

The Article related to ligandable pocket plant homeodomain zinc finger domain drug scanning, Pharmacology: Structure-Activity and other aspects.Safety of 4-(4-Chlorophenyl)piperidin-4-ol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem