Day: November 4, 2022

On February 9, 2017, Buckley, Dennis; Winter, Georg; Phillips, Andrew J.; Heffernan, Timothy; Bradner, James; Roberts, Justin; Nabet, Behnam published a patent.COA of Formula: C14H10N2O6 The title of the patent was Regulation of protein levels using ligand-binding domains for chemical regulation of proteolytic degradation. And the patent contained the following:

A method of modulating protein levels in vivo in a manner that avoids problems associated with CRISPR/Cas gene editing by making the protein susceptible to chem.-induced protein degradation is described. A sequence encoding a protein domain binding a heterobifunctional compound is inserted into the gene of interest, leading to synthesis of the fusion protein. One functional domain of the heterobifunctional compound binds to the fusion protein, and the other binds to a protein that recruits an E3 ubiquitin ligase leading to ubiquitination and degradation The use of FK506-binding proteins as the ligand-binding domains with heterobifunctional FK506 derivatives as the regulating mol. is demonstrated. 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 proteolysis induction fusion protein heterobifunctional ligand ubiquitination, General Biochemistry: Subcellular Processes and other aspects.COA of Formula: C14H10N2O6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Punetha, Ankita; Green, Keith D.; Garzan, Atefeh; Thamban Chandrika, Nishad; Willby, Melisa J.; Pang, Allan H.; Hou, Caixia; Holbrook, Selina Y. L.; Krieger, Kyle; Posey, James E.; Parish, Tanya; Tsodikov, Oleg V.; Garneau-Tsodikova, Sylvie published an article in 2021, the title of the article was Structure-based design of haloperidol analogues as inhibitors of acetyltransferase Eis from Mycobacterium tuberculosis to overcome kanamycin resistance.Application In Synthesis of 4-(4-Chlorophenyl)piperidin-4-ol And the article contains the following content:

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a deadly bacterial disease. Drug-resistant strains of Mtb make eradication of TB a daunting task. Overexpression of the enhanced intracellular survival (Eis) protein by Mtb confers resistance to the second-line antibiotic kanamycin (KAN). Eis is an acetyltransferase that acetylates KAN, inactivating its antimicrobial function. Development of Eis inhibitors as KAN adjuvant therapeutics is an attractive path to forestall and overcome KAN resistance. We discovered that an antipsychotic drug, haloperidol (HPD, 1), was a potent Eis inhibitor with IC50 = 0.39 ± 0.08 μM. We determined the crystal structure of the Eis-haloperidol (1) complex, which guided synthesis of 34 analogs. The structure-activity relationship study showed that in addition to haloperidol (1), eight analogs, some of which were smaller than 1, potently inhibited Eis (IC50 ≤ 1 μM). Crystal structures of Eis in complexes with three potent analogs and droperidol (DPD), an antiemetic and antipsychotic, were determined Three compounds partially restored KAN sensitivity of a KAN-resistant Mtb strain K204 overexpressing Eis. The Eis inhibitors generally did not exhibit cytotoxicity against mammalian cells. All tested compounds were modestly metabolically stable in human liver microsomes, exhibiting 30-60% metabolism over the course of the assay. While direct repurposing of haloperidol as an anti-TB agent is unlikely due to its neurotoxicity, this study reveals potential approaches to modifying this chem. scaffold to minimize toxicity and improve metabolic stability, while preserving potent Eis inhibition. 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 mycobacterium tuberculosis kanamycin resistance haloperidol analog acetyltransferase eis inhibitor, Placeholder for records without volume info and other aspects.Application In Synthesis of 4-(4-Chlorophenyl)piperidin-4-ol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On February 28, 2022, Lier, Svenja; Sellmer, Andreas; Orben, Felix; Heinzlmeir, Stephanie; Krauss, Lukas; Schneeweis, Christian; Hassan, Zonera; Schneider, Carolin; Schaefer, Arlette; Pongratz, Herwig; Engleitner, Thomas; Oellinger, Rupert; Kuisl, Anna; Bassermann, Florian; Schlag, Christoph; Kong, Bo; Dove, Stefan; Kuster, Bernhard; Rad, Roland; Reichert, Maximilian; Wirth, Matthias; Saur, Dieter; Mahboobi, Siavosh; Schneider, Guenter published an article.SDS of cas: 1216805-11-6 The title of the article was A novel Cereblon E3 ligase modulator with antitumor activity in gastrointestinal cancer. And the article contained the following:

Targeted protein degradation offers new opportunities to inactivate cancer drivers and has successfully entered the clinic. Ways to induce selective protein degradation include proteolysis targeting chimera (PROTAC) technol. and immunomodulatory (IMiDs) / next-generation Cereblon (CRBN) E3 ligase modulating drugs (CELMoDs). Here, we aimed to develop a MYC PROTAC based on the MYC-MAX dimerization inhibitor 10058-F4 derivative 28RH and Thalidomide, called MDEG-541. We show that a subgroup of gastrointestinal cancer cell lines and primary patient-derived organoids are MDEG-541 sensitive. Although MYC expression was regulated in a CRBN-, proteasome- and ubiquitin-dependent manner, we provide evidence that MDEG-541 induced the degradation of CRBN neosubstrates, including G1 to S phase transition 1/2 (GSPT1/2) and the Polo-like kinase 1 (PLK1). In sum, we have established a CRBN-dependent degrader of relevant cancer targets with activity in gastrointestinal cancers. The experimental process involved the reaction of 2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindoline-5-carboxylic acid(cas: 1216805-11-6).SDS of cas: 1216805-11-6

The Article related to gastrointestinal cancer plk1 cereblon e3 ligase modulator antitumor, cereblon, gspt1, gspt2, myc, plk1, Placeholder for records without volume info and other aspects.SDS of cas: 1216805-11-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On February 15, 2022, Dichiara, Maria; Artacho-Cordon, Antonia; Turnaturi, Rita; Santos-Caballero, Miriam; Gonzalez-Cano, Rafael; Pasquinucci, Lorella; Barbaraci, Carla; Rodriguez-Gomez, Isabel; Gomez-Guzman, Manuel; Marrazzo, Agostino; Cobos, Enrique J.; Amata, Emanuele published an article.Category: piperidines The title of the article was Dual Sigma-1 receptor antagonists and hydrogen sulfide-releasing compounds for pain treatment: Design, synthesis, and pharmacological evaluation. And the article contained the following:

The development of σ1 receptor antagonists hybridized with a H2S-donor is here reported. We aimed to obtain improved analgesic effects when compared to σ1 receptor antagonists or H2S-donors alone. In an in vivo model of sensory hypersensitivity, thioamide 1a induced analgesia which was synergistically enhanced when associated with the σ1 receptor antagonist BD-1063. The selective σ1 receptor agonist PRE-084 completely reversed this effect. Four thioamide H2S-σ1 receptor hybrids (5a-8a) and their amide derivatives (5b-8b) were synthesized. Compound 7a (AD164) robustly released H2S and showed selectivity for σ1 receptor over σ2 and opioid receptors. This compound induced marked analgesia that was reversed by PRE-084. The amide analog 7b (AD163) showed only minimal analgesia. Further studies showed that 7a exhibited negligible acute toxicity, together with a favorable pharmacokinetic profile. To the best of our knowledge, compound 7a is the first dual-acting ligand with simultaneous H2S-release and σ1 antagonistic activities. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Category: piperidines

The Article related to pain analgesic effect pharmacokinetics antagonism, analgesia, antagonist, dual ligands, hydrogen sulfide donor, sigma-1 receptor, Placeholder for records without volume info and other aspects.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On April 30, 2022, Zhu, Zhenjun; Huang, Rui; Liu, Wei; Wang, Juan; Wu, Shujian; Chen, Mengfei; Huang, Aohuan; Xie, Yizhen; Chen, Moutong; Jiao, Chunwei; Zhang, Jumei; Wu, Qingping; Ding, Yu published an article.Reference of 4-(4-Chlorophenyl)piperidin-4-ol The title of the article was Whole Agrocybe cylindracea Prevented Obesity Linking with Modification of Gut Microbiota and Associated Fecal Metabolites in High-Fat Diet-Fed Mice. And the article contained the following:

Whole-food-based strategies to prevent metabolic diseases are growing interests. Agrocybe cylindracea (AC) is a major edible mushroom with high values of nutrition, but little is known about its health benefits as a portion of whole food. Diet-induced obese, C57BL/6J mice are fed an high-fat diet (HFD) with or without AC (3% or 5%, weight/weight in the diet) for 9 wk. The results show that dietary AC reduced body weight, adipose accumulation, impairment of glucose tolerance, lipid levels, and liver injury in HFD-fed mice. Moreover, AC not only prevents HFD-induced gut disorder, as indicates by the enriched probiotic Bifidobacterium and reduced endotoxin-bearing Proteobacteria, but also improve the lipopolysaccharide (LPS) level and gut tissue structure. Fecal metabolites such as harmine and harmanine are also remarkably altered by AC. Spearman′s correlation anal. reveals that the AC-altered microbes and metabolites are strongly correlated with obesity-related indexes. These findings suggest that dietary AC prevents HFD-induced obesity and its complications in association with modulating gut microbiota and associated fecal metabolites. 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 agrocybe cylindracea prevent obesity gut microbiota metabolite hfd, agrocybe cylindracea, gut microbiota, high-fat diet, metabolites, whole food, Placeholder for records without volume info and other aspects.Reference of 4-(4-Chlorophenyl)piperidin-4-ol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Rampa, Angela; Bartolini, Manuela; Pruccoli, Letizia; Naldi, Marina; Iriepa, Isabel; Moraleda, Ignacio; Belluti, Federica; Gobbi, Silvia; Tarozzi, Andrea; Bisi, Alessandra published an article in 2018, the title of the article was Exploiting the chalcone scaffold to develop multifunctional agents for Alzheimer′s disease.Reference of 4-(4-Chlorophenyl)piperidin-4-ol And the article contains the following content:

Alzheimer′s disease still represents an untreated multifaceted pathol., and drugs able to stop or reverse its progression are urgently needed. In this paper, a series of naturally inspired chalcone-based derivatives was designed as structural simplification of our previously reported benzofuran lead compound, aiming at targeting both acetyl (AChE)- and butyryl (BuChE) cholinesterases that, despite having been studied for years, still deserve considerable attention. In addition, the new compounds could also modulate different pathways involved in disease progression, due to the peculiar trans-a,β-unsaturated ketone in the chalcone framework. All mols. presented in this study were evaluated for cholinesterase inhibition on the human enzymes and for antioxidant and neuroprotective activities on a SH-SY5Y cell line. The results proved that almost all the new compounds were low micromolar inhibitors, showing different selectivity depending on the appended substituent; some of them were also effective antioxidant and neuroprotective agents. In particular, compound 4, endowed with dual AChE/BuChE inhibitory activity, was able to decrease ROS formation and increase GSH levels, resulting in enhanced antioxidant endogenous defense. Moreover, this compound also proved to counteract the neurotoxicity elicited by Aβ1-42 oligomers, showing a promising neuroprotective potential. 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 alzheimer disease chalcone scaffold cholinesterase antioxidant neuroprotective, alzheimer’s disease, antioxidants, chalcones, cholinesterase inhibitors, neuroprotection, Placeholder for records without volume info and other aspects.Reference of 4-(4-Chlorophenyl)piperidin-4-ol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On October 31, 2020, Neganova, Margarita E.; Klochkov, Sergey G.; Pukhov, Sergey A.; Afanasieva, Svetlana V.; Aleksandrova, Yulia R.; Yandulova, Ekaterina Y.; Avila-Rodriguez, Marco F.; Mikhaleva, Liudmila M.; Nikolenko, Vladimir N.; Somasundaram, Siva G.; Kirkland, Cecil E.; Aliev, Gjumrakch published an article.Related Products of 39512-49-7 The title of the article was Synthesis and Cytotoxic Activity of Azine Derivatives of 6-Hydroxyxanthanodiene. And the article contained the following:

Background: The conjugates of the sesquiterpene lactone of the eremophilane series of 6-hydroxyxanthanodiene with hydrogenated azines (piperidines and piperazines) have been synthesized and identified by NMR spectrometer. Objective: A lactone with an unusual skeleton “6-hydroxyxanthanodiene” was extracted from the plant Elecampane (Inula helenium L) and identified various species with NMR spectrometer. Methods: The cytotoxic, mitochondrial, and antioxidant activities on different tumor lines such as A549, HCT116, RD and Jurkat were investigated and determined possible mechanisms. Results: The results showed that the most potent compound was IIIi exhibiting highest cytotoxicity against RD cells (IC50 25.23 ± 0.04 μM), depolarized the mitochondrial membrane and was an effective antioxidant (IC50 inhibition of LP 10.68 ± 3.21 μM) without any toxic side effect on healthy cells. Conclusion: The conjugates of sesquiterpene lactone 6-hydroxyxanthanodiene III and hydrogenated azines may help to design potential promising anticancer drugs. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).Related Products of 39512-49-7

The Article related to hydroxyxanthanodiene azine derivative cytotoxicity anticancer drug, 6-hydroxyxanthanodiene, anticancer drug, antioxidants, apoptosis, azines, cytotoxicity, mitochondria, Placeholder for records without volume info and other aspects.Related Products of 39512-49-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On January 6, 2022, Anderson, Kenneth C.; Hideshima, Teru; Dhe-Paganon, Sirano; Seo, Hyuk-Soo; Mizutani, Takashi; Zhang, Tinghu published a patent.Category: piperidines The title of the patent was PRPK inhibitors. And the patent contained the following:

This disclosure relates to compounds of formula (I) as defined in the Specification. This disclosure also relates to methods of synthesizing the compound of formula I and using the compounds of formula I for treating a disease (e.g., cancer). 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 prpk inhibitor cancer, Pharmaceuticals: Formulation and Compounding and other aspects.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

On August 6, 2020, U. Dighe, Shashikant; Julia, Fabio; Luridiana, Alberto; Douglas, James J.; Leonori, Daniele published an article.HPLC of Formula: 39512-49-7 The title of the article was A photochemical dehydrogenative strategy for aniline synthesis. And the article contained the following:

Chem. reactions that reliably join two mol. fragments together (cross-couplings) are essential to the discovery and manufacture of pharmaceuticals and agrochems.1,2. The introduction of amines onto functionalized aromatics at specific and pre-determined positions (ortho vs. meta vs. para) is currently achievable only in transition-metal-catalyzed processes and requires halogen- or boron-containing substrates3-6. The introduction of these groups around the aromatic unit is dictated by the intrinsic reactivity profile of the method (electrophilic halogenation or C-H borylation) so selective targeting of all positions is often not possible. Here we report a non-canonical cross-coupling approach for the construction of anilines, exploiting saturated cyclohexanones as aryl electrophile surrogates. Condensation between amines and carbonyls, a process that frequently occurs in nature and is often used by (bio-)organic chemists7, enables a predetermined and site-selective carbon-nitrogen (C-N) bond formation, while a photoredox- and cobalt-based catalytic system progressively desaturates the cyclohexene ring en route to the aniline. Given that functionalized cyclohexanones are readily accessible with complete regiocontrol using the well established carbonyl reactivity, this approach bypasses some of the frequent selectivity issues of aromatic chem. We demonstrate the utility of this C-N coupling protocol by preparing com. medicines and by the late-stage amination-aromatization of natural products, steroids and terpene feedstocks. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).HPLC of Formula: 39512-49-7

The Article related to aniline preparation photochem dehydrogenative amination, General Organic Chemistry: Synthetic Methods and other aspects.HPLC of Formula: 39512-49-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Kumar, Rayala Naveen; Meshram, H. M. published an article in 2016, the title of the article was ‘Claycop’ catalyzed highly efficient and chemoselective aza-Michael addition under solvent free condition.HPLC of Formula: 39512-49-7 And the article contains the following content:

A chemoselective and highly efficient addition of amines to electron deficient alkenes is described in the presence of claycop in solvent free condition. The reaction is very rapid and exhibited higher yields in comparison with slurry reaction. Claycop can be readily recovered and reused after activation. This method is suitable for a variety of amines and alkenes. Solvent free condition and recyclability of supported catalyst makes procedure more environmental friendly. The experimental process involved the reaction of 4-(4-Chlorophenyl)piperidin-4-ol(cas: 39512-49-7).HPLC of Formula: 39512-49-7

The Article related to electron deficient alkene amine addition claycop solvent free condition, General Organic Chemistry: Synthetic Methods and other aspects.HPLC of Formula: 39512-49-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem