Category: piperidines

On July 30, 2012, Zhang, Wei; Chen, Niangen; Huang, Jian; Zhai, Ruirui; Fu, Naiguang published an article.Application of 39512-49-7 The title of the article was Study on synthetic and salifying process of loperamide hydrochloride. And the article contained the following:

To study the preparation of the synthetic process of loperamide hydrochloride, a drug which was widely used in the treatment of acute diarrhea with low side effect. Loperamide hydrochloride was synthesized from 2, 2-diphenyl-4-hydroxybutyric acid-γ-lactone as raw material via ring-opening, SN2 substitution, acidylation, quaternization, condensation and salifying. In the first step, when the reaction time was 24 h and temperature was 25°C, the yield was 81%. In the second step, when the molar ratio of n(SOCl2):n(2,2-phenyl-4-bromobutyric acid)=2:1 and temperature was reflux, the content of 4-bromo-2, 2-diphenylbutyroyl chloride(4) was 97.25%. And the key intermediate dimethyl(tetrahydro-3, 3-diphenyl-2-furylidene)ammonium bromide(5) was obtained with the yield increased from 50%(literature reported) to 68% when the molar ratio of n(4):n(Na2CO3):dimethylamine=1.0:1.2:1.5 and temperature was 0∼5°C. When the molar ratio of n(5):n(4-p-chlorophenyl-4-piperidinol):n(Na2CO3)=1.0:1.2:1.1, loperamide(6) was obtained with yield of 85%. After simple salification, the target compound 1 was synthesized from(6) with the yield of 89.6%. The overall yield was 34% and its structure was characterized by IR, 1H-NMR, 13C-NMR and MS spectra. Some drawbacks in the literature was improved and the method was easy for synthesis and suitable for industrial manufacturing The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Application of 39512-49-7

The Article related to loperamide hydrochloride synthetic salifying process, Pharmacology: Methods and other aspects.Application of 39512-49-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On March 16, 2018, Ishoey, Mette; Chorn, Someth; Singh, Natesh; Jaeger, Martin G.; Brand, Matthias; Paulk, Joshiawa; Bauer, Sophie; Erb, Michael A.; Parapatics, Katja; Muller, Andre C.; Bennett, Keiryn L.; Ecker, Gerhard F.; Bradner, James E.; Winter, Georg E. published an article.COA of Formula: C14H10N2O6 The title of the article was Translation Termination Factor GSPT1 Is a Phenotypically Relevant Off-Target of Heterobifunctional Phthalimide Degraders. And the article contained the following:

Protein degradation is an emerging therapeutic strategy with a unique mol. pharmacol. that enables the disruption of all functions associated with a target. This is particularly relevant for proteins depending on mol. scaffolding, such as transcription factors or receptor tyrosine kinases (RTKs). To address tractability of multiple RTKs for chem. degradation by the E3 ligase CUL4-RBX1-DDB1-CRBN (CRL4CRBN), we synthesized a series of phthalimide degraders based on the promiscuous kinase inhibitors sunitinib and PHA665752. While both series failed to induce degradation of their consensus targets, individual mols. displayed pronounced efficacy in leukemia cell lines. Orthogonal target identification supported by mol. docking led us to identify the translation termination factor G1 to S phase transition 1 (GSPT1) as a converging off-target, resulting from inadvertent E3 ligase modulation. This research highlights the importance of monitoring degradation events that are independent of the resp. targeting ligand as a unique feature of small-mol. degraders. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).COA of Formula: C14H10N2O6

The Article related to sunitinib pha665752 phthalimide synthesis antitumor translation termination factor gspt1, Pharmacology: Structure-Activity and other aspects.COA of Formula: C14H10N2O6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On September 21, 2018, Steinebach, Christian; Lindner, Stefanie; Udeshi, Namrata D.; Mani, Deepak C.; Kehm, Hannes; Koepff, Simon; Carr, Steven A.; Guetschow, Michael; Kroenke, Jan published an article.Computed Properties of 1216805-11-6 The title of the article was Homo-PROTACs for the Chemical Knockdown of Cereblon. And the article contained the following:

The immunomodulatory drugs (IMiDs) thalidomide, lenalidomide, and pomalidomide, all approved for the treatment of multiple myeloma, induce targeted ubiquitination and degradation of Ikaros (IKZF1) and Aiolos (IKZF3) via the cereblon (CRBN) E3 ubiquitin ligase. IMiD-based proteolysis-targeting chimeras (PROTACs) can efficiently recruit CRBN to a protein of interest, leading to its ubiquitination and proteasomal degradation By linking two pomalidomide mols., we designed homobifunctional, so-called homo-PROTACs and investigated their ability to induce self-directed ubiquitination and degradation The homodimerized compound I was characterized as a highly potent and efficient CRBN degrader with only minimal effects on IKZF1 and IKZF3. The cellular selectivity of I for CRBN degradation was confirmed at the proteome level by quant. mass spectrometry. Inactivation by compound I did not affect proliferation of different cell lines, prevented pomalidomide-induced degradation of IKZF1 and IKZF3, and antagonized the effects of pomalidomide on multiple myeloma cells. Homobifunctional CRBN degraders will be useful tools for future biomedical investigations of CRBN-related signaling and may help to further elucidate the mol. mechanism of thalidomide analogs. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Computed Properties of 1216805-11-6

The Article related to phthalimido glutarimide synthesis antitumor cereblon ikzf1 ikzf3 multiple myeloma, Pharmacology: Structure-Activity and other aspects.Computed Properties of 1216805-11-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On February 1, 2012, Peprah, Kwakye; Zhu, Xue Y.; Eyunni, Suresh V. K.; Setola, Vincent; Roth, Bryan L.; Ablordeppey, Seth Y. published an article.Application In Synthesis of 4-(4-Chlorophenyl)piperidin-4-ol The title of the article was Multi-receptor drug design: Haloperidol as a scaffold for the design and synthesis of atypical antipsychotic agents. And the article contained the following:

Using haloperidol as a scaffold, new agents were designed to investigate the structural contributions of various groups to binding at CNS receptors associated with atypical antipsychotic pharmacol. It is clear that each pharmacophoric group, the butyrophenone, the piperidine and the 4-chlorophenyl moieties contributes to changes in binding to the receptors of interest. This strategy has resulted in the identification of several new agents, compounds 16, 18, 19, 23, 24 and 25, with binding profiles which satisfy our stated criteria for agents to act as potential atypical antipsychotics. This research demonstrates that haloperidol can serve as a useful lead in the identification and design of new agents that target multiple receptors associated with antipsychotic pharmacol. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Application In Synthesis of 4-(4-Chlorophenyl)piperidin-4-ol

The Article related to haloperidol scaffold design synthesis atypical antipsychotic structure, Pharmacology: Structure-Activity and other aspects.Application In Synthesis of 4-(4-Chlorophenyl)piperidin-4-ol

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

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 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 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 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 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