Month: November 2022

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 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 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 January 1, 2014, Gitto, Rosaria; De Luca, Laura; Ferro, Stefania; Scala, Angela; Ronsisvalle, Simone; Parenti, Carmela; Prezzavento, Orazio; Buemi, Maria Rosa; Chimirri, Alba published an article.Formula: C11H14ClNO The title of the article was From NMDA receptor antagonists to discovery of selective σ2 receptor ligands. And the article contained the following:

Following previous studies focused on the search for new mols. targeting GluN2B-containing NMDA, a small series of 1-(1H-indol-3-yl)-2-(4-phenylpiperidin-1-yl)ethanone derivatives has been synthesized by using Microwave Assisted Organic Synthesis (MAOS). Given that GluN2B ligands frequently exert off-target effects we also tested their affinity towards sigma receptors. Binding assay revealed that only the 1-(5-hydroxy-1H-indol-3-yl)-2-(4-phenylpiperidin-1-yl)ethanone (7a) retained GluN2B affinity. Interestingly, the 5-methoxyindoles 5a and 6a were efficient and selective ligands toward σ2 receptor (Ki values of 10 nM and 20 nM, resp.). Thus, in this case the discovery of new σ2 receptor selective ligands was an unexpected result emerging from the screening of cross-activity against other CNS receptors. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Formula: C11H14ClNO

The Article related to indole derivative preparation binding glun2b nmda receptor structure, glun2b/nmda, glutamate, ifenprodil, indoles, sigma receptor, Pharmacology: Structure-Activity and other aspects.Formula: C11H14ClNO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On October 15, 2015, Kusumi, Kensuke; Shinozaki, Koji; Yamaura, Yoshiyuki; Hashimoto, Ai; Kurata, Haruto; Naganawa, Atsushi; Ueda, Hideyuki; Otsuki, Kazuhiro; Matsushita, Takeshi; Sekiguchi, Tetsuya; Kakuuchi, Akito; Seko, Takuya published an article.Safety of 4-(4-Chlorophenyl)piperidin-4-ol The title of the article was Discovery of novel S1P2 antagonists. Part 2: Improving the profile of a series of 1,3-bis(aryloxy)benzene derivatives. And the article contained the following:

The initial lead compound was modified to improve its metabolic stability. The resulting compound showed excellent metabolic stability in rat and human liver microsomes. The authors subsequently designed and synthesized compound N-[3-[4-(aminocarbonyl)phenoxy]-5-(4-fluorophenoxy)phenyl]-4-(4-chlorophenyl)-4-hydroxy-1-piperidinecarboxamide (I), which showed improved S1P2 antagonist activity and good metabolic stability. The subsequent introduction of a carboxylic acid moiety into I resulted in 4-[3-(4-fluorophenoxy)-5-[[[4-(4-fluorophenyl)-4-hydroxy-1-piperidinyl]carbonyl]amino]phenoxy]benzoic acid (II), which showed potent antagonist activity towards S1P2 with a much smaller species difference between human S1P2 and rat S1P2. Compound II also showed good metabolic stability and an improved safety profile compared with compound I. 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 aryloxybenzene preparation pharmacokinetics, antagonist, g protein-coupled receptors, metabolic stability, sphingosine-1-phosphate receptor 2, Pharmacology: Structure-Activity and other aspects.Safety of 4-(4-Chlorophenyl)piperidin-4-ol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Burslem, George M.; Ottis, Philipp; Jaime-Figueroa, Saul; Morgan, Alicia; Cromm, Philipp M.; Toure, Momar; Crews, Craig M. published an article in 2018, the title of the article was Efficient Synthesis of Immunomodulatory Drug Analogues Enables Exploration of Structure-Degradation Relationships.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid And the article contains the following content:

The immunomodulatory drugs (IMiDs) thalidomide, pomalidomide, and lenalidomide have been approved for the treatment of multiple myeloma for many years. Recently, their use as E3 ligase recruiting elements for small-mol.-induced protein degradation has led to a resurgence in interest in IMiD synthesis and functionalization. Traditional IMiD synthesis follows a stepwise route with multiple purification steps. Herein we describe a novel one-pot synthesis without purification that provides rapid access to a multitude of IMiD analogs. Binding studies with the IMiD target protein cereblon (CRBN) reveals a narrow structure-activity relationship with only a few compounds showing sub-micromolar binding affinity in the range of pomalidomide and lenalidomide. However, anti-proliferative activity as well as Aiolos degradation could be identified for two IMiD analogs. This study provides useful insight into the structure-degradation relationships for mols. of this type as well as a rapid and robust method for IMiD synthesis. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

The Article related to immunomodulator analog preparation structure protein degradation, cereblon, condensation reactions, imides, immunomodulatory drugs, protein degradation, Pharmacology: Structure-Activity and other aspects.Safety of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On August 15, 2016, Etukala, Jagan R.; Zhu, Xue Y.; Eyunni, Suresh V. K.; Onyameh, Edem K.; Ofori, Edward; Bricker, Barbara A.; Kang, Hye J.; Huang, Xi-Ping; Roth, Bryan L.; Ablordeppey, Seth Y. published an article.Computed Properties of 39512-49-7 The title of the article was Development of CNS multi-receptor ligands: Modification of known D2 pharmacophores. And the article contained the following:

Several known D2 pharmacophores have been explored as templates for identifying ligands with multiple binding affinities at dopamine and serotonin receptors considered as clin. relevant receptors in the treatment of neuropsychiatric diseases. This approach has resulted in the identification of ligands that target multiple CNS receptors while avoiding others associated with deleterious effects. Three compounds including I may have potential for further development as antipsychotic agents as they favorably interact with the clin. relevant receptors including D2R, 5-HT1AR, and 5-HT7R. The authors have also identified the pair of compounds I and II as high affinity D2R ligands with and without SERT binding affinities, resp. These differential binding profiles endow the pair with the potential for evaluating SERT contributions to antipsychotic drug activity in animal behavioral models. In addition, compound I has no significant affinity for 5-HT2CR and binds only moderately to the H1R, suggesting it may not induce weight gain or sedation when used clin. Taken together, compound I displays an interesting pharmacol. profile that necessitates the evaluation of its functional and in vivo effects in animal models which are currently ongoing. 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 central nervous system receptor ligand d2 pharmacophore antipsychotic, antipsychotic, cns receptor, dopamine receptor ligands, multi-receptor targeting, pharmacophore, Pharmacology: Structure-Activity and other aspects.Computed Properties of 39512-49-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On March 9, 2022, Rodrigalvarez, Jesus; Reeve, Luke A.; Miro, Javier; Gaunt, Matthew J. published an article.Formula: C11H14ClNO The title of the article was Pd(II)-Catalyzed Enantioselective C(sp3)-H Arylation of Cyclopropanes and Cyclobutanes Guided by Tertiary Alkylamines. And the article contained the following:

Here, a palladium-catalyzed enantioselective C(sp3)-H arylation of aminomethyl-cyclopropanes I [R = H, Me, (CH2)2OMe, 4-ClC6H44; R1 = NMe2, NEt2, N-piperidinyl, etc.; Ar = Ph, 2-naphthyl, 6-Cl-3-pyridinyl, etc.; n = 1] and -cyclobutanes I [n = 2] with aryl boronic acids was reported. A range of native tertiary alkylamine groups were able to direct C-H cleavage and forge carbon-aryl bonds on the strained cycloalkanes framework as single diastereomers and with excellent enantiomeric ratios. Central to the success of this strategy was the use of a simple N-acetyl amino acid ligand, which not only controls the enantioselectivity but also promotes γ-C-H activation of over other pathways. Computational anal. of the cyclopalladation step provided an understanding of how enantioselective C-H cleavage occurred and revealed distinct transition structures to our previous work on enantioselective desymmetrization of N-iso-Bu tertiary alkylamines. This straightforward and operationally simple method simplified the construction of functionalized aminomethyl-strained cycloalkanes, which was believed will find widespread use in academic and industrial settings relating to the synthesis of biol. active small mols. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Formula: C11H14ClNO

The Article related to diarylated aminomethyl cycloalkane enantioselective preparation, aminomethyl cycloalkane palladium catalyzed enantioselective arylation, Alicyclic Compounds: Cyclobutanes and other aspects.Formula: C11H14ClNO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On April 30, 2018, Mieszkowski, Dominik; Sroka, Wiktor Dariusz; Marszall, Michat Piotr published an article.Category: piperidines The title of the article was Ionic liquids as separation enhancers of haloperidol and its two metabolites in high-performance thin-layer chromatography supported with mass spectrometry. And the article contained the following:

High-performance thin-layer chromatog. (HPTLC)-densitometric method of haloperidol (HP) and its two metabolites (reduced haloperidol [RHP], 4-(4-chlorophenyl)-4-hydroxypiperidine [CPHP]) from human plasma has been developed by use of mobile-phase additives. The influence of the type of inorganic/organic additive on the retention of the studied compounds was evaluated. The chromatog. process was carried out with traditional mobile phase modifiers and 1-alkyl-imidazolium ionic liquid as separation enhancers, in the presence of chlorpromazine as internal standard 1-Ethyl-3-methylimidazolium tetrafluoroborate ([emim][BF4]) ionic liquid offered good selectivity in comparison with traditional mobile phase additives. The studied drugs were well distributed as the RF values were 0.31 for chlorpromazine hydrochloride (CPZ), 0.38 for HP, 0.44 for CPHP, and 0.58 for RHP, resp., with no apparent broadening and overlapping of spots. The test compounds were extracted using acetonitrile as precipitation agent. The identity of the bands from human plasma was addnl. confirmed by rapid and contamination-free CAMAG thin-layer chromatog.-mass spectrometry (TLC-MS) interface. The limit of detection (LOD) values obtained by densitometry scanning were 0.1807, 0.3158, and 0.3924μg spot-1 (for HP, RHP, and CPHP), whereas the limit of quantification (LOQ) values for the presented method were 0.5476, 0.9570, and 1.1892μg spot-1 (for HP, RHP, and CPHP). Recovery values of all tested compounds were in the range from 95.43% to 99.60% (intra-day) and 96.13% to 103.18% (inter-day);%RSD did not exceed the value of 5%. The results confirm the pos. effect of ionic liquids in the separation process related to their silanol blocking properties and their suitability for use in thin-layer chromatog./mass spectrometry method. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Category: piperidines

The Article related to ionic liquid haloperidol metabolite thin layer chromatog mass spectrometry, Organic Analytical Chemistry: Other and other aspects.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On April 30, 2014, Chai, Christina L. L.; Teo, Serena L. M.; Jameson, Felicity K. M.; Lee, Serina S. C.; Likhitsup, Asawin; Chen, Chia-Lung; Rittschof, Dan published an article.Synthetic Route of 39512-49-7 The title of the article was Loperamide-based compounds as additives for biofouling management. And the article contained the following:

The com. pharmaceutical Imodium, which contains the active ingredient loperamide hydrochloride, has been shown to have biofouling control properties. However, due to concerns associated with safety and persistence of this active pharmaceutical ingredient (API) in the environment, the development of loperamide as an anti-fouling additive is not desirable. In this paper, we report our efforts directed towards the design and synthesis of small mol. anti-foulants using the loperamide parent compound as the lead compound These loperamide-based compounds can be synthesized readily and inexpensively. Several of the compounds identified are potentially useful as additives in marine antifouling coatings as they control attachment of barnacles in laboratory tests and an estimation program (BIOWIN) developed by the US Environmental Protection Agency predicts that they will degrade completely in weeks to months. 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 balanus loperamide additive marine antifouling coating material, Agrochemical Bioregulators: Microbial and other aspects.Synthetic Route of 39512-49-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem