Day: October 18, 2022

Yang, Hao; Murigi, Francis N.; Wang, Zhijian; Li, Junfeng; Jin, Hongjun; Tu, Zhude published an article on February 15 ,2015. The article was titled 《Synthesis and in vitro characterization of cinnoline and benzimidazole analogues as phosphodiesterase 10A inhibitors》, and you may find the article in Bioorganic & Medicinal Chemistry Letters.Name: 4-(Pyridin-3-yl)piperidin-4-ol The information in the text is summarized as follows:

Fifteen cinnoline analogs and six benzimidazole phosphodiesterase 10A (PDE10A) inhibitors were synthesized as potential PET radiopharmaceuticals and their in vitro activity as PDE10A inhibitors was determined Nine out of twenty-one compounds were potent inhibitors of PDE10A with IC50 values ranging from 1.5 to 18.6 nM. Notably, the IC50 values of compounds I [R = H, F] and II were 1.52 ± 0.18, 2.86 ± 0.10, and 3.73 ± 0.60 nM, resp.; these three compounds also showed high in vitro selectivity (>1000-fold) for PDE10A over PDE 3A/3B, PDE4A/4B. The high potency and selectivity of these three compounds suggests that they could be radiolabeled with PET radionuclides for further evaluation of their in vivo pharmacol. behavior and ability to quantify PDE10A in the brain. After reading the article, we found that the author used 4-(Pyridin-3-yl)piperidin-4-ol(cas: 50461-59-1Name: 4-(Pyridin-3-yl)piperidin-4-ol)

4-(Pyridin-3-yl)piperidin-4-ol(cas: 50461-59-1) belongs to piperidines. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions. Name: 4-(Pyridin-3-yl)piperidin-4-ol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2018,European Journal of Medicinal Chemistry included an article by Bai, Zhongjie; Zhang, Jinlong; Zhang, Qiuping; Zhang, Taofeng; Li, Jili; Zhao, Quanyi; Wang, Zhen; He, Dian; Cheng, Jie; Zhang, Jingke; Liu, Bin. Reference of 2-(Piperidin-4-yl)ethanol. The article was titled 《Synthesis, toxicities and bio-activities of manganese complexes with CO and H2S dual donors》. The information in the text is summarized as follows:

A series of H2S-CO dual-donors [Mn(CO)4CS2NR1R2] was synthesized, and evaluated from toxicity and bioactivity. The CO-H2S measuring test showed all the complexes not only released CO, but released H2S. The resulting data of cytotoxicity showed all the complexes had activities against the cell proliferation; among them, complexes 1, 2 and 7 displayed higher activities than the others, and their potencies were close to cis-platinum (DDP); whereas the precursors A1-A22 had almost no activities against all five tumor cell lines and W138 cell line proliferation. It is worth noting that complex 1 displayed the highest activity to MCF-7, complex 2 displayed the highest activity to HePG2, and complex 7 showed selectivity inhibition to both A549 and HeLa. The developmental toxicities of the complex were assessed using zebrafish embryos. The results showed complexes 1 and 2 had effect on the mortality and hatching rate of zebrafish embryos in dose-dependent manner. They caused zebrafish malformations when they were over 10 μM. Meanwhile, they displayed dose-dependent toxicities to larval zebrafish. In the test of bio-activities, complexes 1 and 2 had strong anti-inflammatory activities; they not only down-regulated the expression levels of iNOS and TNF-α, up-regulated the expression of HO-1 and IL-10, but also up-regulated COX-2 levels. In contrast, the precursor compound (A1 or A2) displayed lower anti-inflammatory activity than the corresponding complex, which suggests both the CO and H2S from the complex took synergistic effects in the process of anti-inflammation. In addition, the complex showed antihypertensive effect and myocardial protection. This effect also possibly resulted from this synergistic effect. All these suggest the complexes have potential to be candidate medicines. After reading the article, we found that the author used 2-(Piperidin-4-yl)ethanol(cas: 622-26-4Reference of 2-(Piperidin-4-yl)ethanol)

2-(Piperidin-4-yl)ethanol(cas: 622-26-4) can be used to synthese ursolic acid derivatives, spiroimidazolidinone NPC1L1 inhibitors, neurokinin-2 receptor antagonists, antagonists for inhibition of platelet aggregation.Reference of 2-(Piperidin-4-yl)ethanol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

The author of 《Discovery of Evobrutinib: An Oral, Potent, and Highly Selective, Covalent Bruton’s Tyrosine Kinase (BTK) Inhibitor for the Treatment of Immunological Diseases》 were Caldwell, Richard D.; Qiu, Hui; Askew, Ben C.; Bender, Andrew T.; Brugger, Nadia; Camps, Montserrat; Dhanabal, Mohanraj; Dutt, Vikram; Eichhorn, Thomas; Gardberg, Anna S.; Goutopoulos, Andreas; Grenningloh, Roland; Head, Jared; Healey, Brian; Hodous, Brian L.; Huck, Bayard R.; Johnson, Theresa L.; Jones, Christopher; Jones, Reinaldo C.; Mochalkin, Igor; Morandi, Federica; Nguyen, Ngan; Meyring, Michael; Potnick, Justin R.; Santos, Dusica Cvetinovic; Schmidt, Ralf; Sherer, Brian; Shutes, Adam; Urbahns, Klaus; Follis, Ariele Viacava; Wegener, Ansgar A.; Zimmerli, Simone C.; Liu-Bujalski, Lesley. And the article was published in Journal of Medicinal Chemistry in 2019. Safety of tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:

Bruton’s tyrosine kinase (BTK) inhibitors such as ibrutinib hold a prominent role in the treatment of B cell malignancies. However, further refinement is needed to this class of agents, particularly in terms of adverse events (potentially driven by kinase promiscuity), which preclude their evaluation in nononcol. indications. Here, we report the discovery and preclin. characterization of evobrutinib, a potent, obligate covalent inhibitor with high kinase selectivity. Evobrutinib displayed sufficient preclin. pharmacokinetic and pharmacodynamic characteristics which allowed for in vivo evaluation in efficacy models. Moreover, the high selectivity of evobrutinib for BTK over epidermal growth factor receptor and other Tec family kinases suggested a low potential for off-target related adverse effects. Clin. investigation of evobrutinib is ongoing in several autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus.tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Safety of tert-Butyl 4-aminopiperidine-1-carboxylate) was used in this study.

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Acylation is one of the most important reactions of primary and secondary amines; a hydrogen atom is replaced by an acyl group (a group derived from an acid, such as RCOOH or RSO3H, by removal of ―OH, such as RC(=O)―, RS(O)2―, and so on). Reagents may be acid chlorides (RCOC1, RSO2C1), anhydrides ((RCO)2O), or even esters (RCOOR′); the products are amides of the corresponding acids.Safety of tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Chloroquine fumardiamides as novel quorum sensing inhibitors》 was published in Bioorganic & Medicinal Chemistry Letters in 2020. These research results belong to Beus, Maja; Savijoki, Kirsi; Patel, Jayendra Z.; Yli-Kauhaluoma, Jari; Fallarero, Adyary; Zorc, Branka. Name: tert-Butyl 4-aminopiperidine-1-carboxylate The article mentions the following:

In our study, a set of twenty-six fumardiamides with a quinoline head-group were evaluated as potential QSIs. Two strains of Gram-neg. Chromobacterium violaceum (violacein-producing strain ATCC31532 and violacein-neg., mini-Tn5 mutant derivative CV026) were used as QS reporters for testing anti-QS and bactericidal activity of various quinoline fumardiamides. The initial screening of eighteen fumardiamides with primaquine, mefloquine and chloroquine scaffolds identified chloroquine derivatives as the most promising QSIs. Tail-group optimization of chloroquine fumardiamides led to the most active compounds 27, 29 and 30 bearing aminoethyl or piperidine moieties. At 400 μM concentration, these compounds inhibited the QS of C. violaceum strains in a manner similar to quercetin (the model QSI), while at the 40 μM concentration their inhibitory effect was twice less than that of quercetin. As none of the compounds displayed a bactericidal effect and that the QS inhibition was specific to the CV026 strain, our findings indicate that the structurally optimized chloroquine derivatives could function as quorum quenching (QQ) agents with a potential to block the signaling without entering the cell. In conclusion, our finding provides an important step toward the further design of agents targeting cell-to-cell communication. The experimental process involved the reaction of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Name: tert-Butyl 4-aminopiperidine-1-carboxylate)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.Name: tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Tang, Weiqin; Mu, Tong; Che, Xuefu; Dong, Jianhao; Yang, Jingshuai published their research in ACS Sustainable Chemistry & Engineering in 2021. The article was titled 《Highly Selective Anion Exchange Membrane Based on Quaternized Poly(triphenyl piperidine) for the Vanadium Redox Flow Battery》.Recommanded Product: 1445-73-4 The article contains the following contents:

Vanadium redox flow batteries (VRFBs) have attracted great attention recently owing to the increasing supply of intermittent renewable energies. However, VRFBs usually suffer from serious vanadium ion crossover and high cost when perfluorinated membranes are employed as the separator. In this study, a highly selective anion exchange membrane (AEM) is synthesized from the aryl ether-free poly(terphenyl piperidine) (PTP). Using 3-chloro-2-hydroxypropyltrimethyl ammonium chloride (CHPTMA-Cl) as the quaternization reagent, not only are the piperidinium cations formed in the PTP main chain, but also the side-chain quaternary ammonium cation and hydroxyl group are introduced into the PTP backbone. Compared with pure PTP-TFA and Me quaternized PTP (PTP-Me) membranes, the obtained hydroxypropyltrimethyl ammonium grafted poly(terphenyl piperidinium) (PTP-CHPTMA) membrane exhibits high H+ permeability (1.82 x 10-5 cm2 min-1) and low area resistance (0.35 Ω cm2) mainly due to the presence of the hydrophilic hydroxyl group. Owing to the electrostatic repulsion effect of main-chain piperidinium and side-chain quaternary ammonium cations to vanadium ions, the PTP-CHPTMA membrane achieves a low vanadium ion permeability (1.21 x 10-8 cm2 min-1). Consequently, the PTP-CHPTMA membrane reaches 2 orders of magnitude higher ion selectivity than Nafion 115. The assembled single VRFB with PTP-CHPTMA possesses high Coulombic efficiencies of close to 100% at 60-160 mA cm-2 and higher energy efficiencies than the cell with Nafion 115. The self-discharge duration of the cell with PTP-CHPTMA (381 h) is nearly 4.5 times longer than that of Nafion 115 (86 h). Meanwhile, the VRFB based on PTP-CHPTMA displays excellent cycle stability and discharge capacity retention over 580 charge-discharge cycles at 100 mA cm-2. The results came from multiple reactions, including the reaction of 1-Methyl-4-piperidone(cas: 1445-73-4Recommanded Product: 1445-73-4)

1-Methyl-4-piperidone(cas: 1445-73-4) is a member of piperidine. Piperidine is ubiquitous structural motif widely occurred in diverse synthetically and naturally occurring bioactive molecules. Piperidines are an immensely important class of compounds medicinally: the piperidine ring is the most common heterocyclic subunit among FDA approved drugs.Recommanded Product: 1445-73-4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Zha, Liang; Xie, Yunfeng; Wu, Chengyao; Lei, Ming; Lu, Xueer; Tang, Wenjian; Zhang, Jing published an article in European Journal of Medicinal Chemistry. The title of the article was 《Novel benzothiazole-urea hybrids: Design, synthesis and biological activity as potent anti-bacterial agents against MRSA》.Category: piperidines The author mentioned the following in the article:

Novel benzothiazole-urea hybrids were designed, synthesized and evaluated for their anti-bacterial activity. They only exhibited anti-bacterial activity against Gram-pos. bacteria, including clin. methicillin-resistant S. aureus (MRSA), compounds I (R = 4-CF3C6H4NH, 2,4-F2C6H3NH), II (R1 = H, R2 = 4-CF3C6H4NH), II (R1 = Cl, R2 = 4-CF3C6H4NH), and II (R1 = Cl, R2 = 2,4-F2C6H3NH) exhibited potent activity (MIC = 0.39 and 0.39/0.78μM against SA and MRSA, resp.). Crystal violet assay showed that compounds I (R = 4-CF3C6H4NH) II (R1 = H, R2 = 4-CF3C6H4NH), and II (R1 = Cl, R2 = 2,4-F2C6H3NH) not only inhibited the formation of biofilms but also eradicated preformed biofilms. Compound II (R1 = Cl, R2 = 2,4-F2C6H3NH) had membrane disruption, little propensity to induce resistance, benign safety and in vivo anti-MRSA efficacy in a mouse model of abdominal infection. Therefore, authors data demonstrated the potential to advance benzothiazole-urea hybrids as a new class of antibiotics. In the part of experimental materials, we found many familiar compounds, such as tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Category: piperidines)

tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas:109384-19-2) is a 4-hydroxypyridine with a boc protecting group used in the preparation of neurologically active agents and other pharmaceutical compounds.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Villegas, Alondra; Satheeshkumar, Rajendran; Ballesteros-Casallas, Andres; Paulino, Margot; Castro, Alejandro; Espinosa-Bustos, Christian; Salas, Cristian O. published an article in Journal of Heterocyclic Chemistry. The title of the article was 《Convergent synthesis, drug target prediction, and docking studies of new 2,6,9-trisubstituted purine derivatives》.Application of 87120-72-7 The author mentioned the following in the article:

A set of new 2,6,9-trisubstituted purine derivatives were designed and synthesized from 6-chloro-2-fluoro-9-alkyl-9H-purine as the key starting material. These purines were synthesized via a multistep protocol and finally subjected to SNAr with various aminopiperidinyl salts. The structures of these compounds were established by substantiating them through spectral techniques like FT-IR, 1H-NMR, 13C-NMR, and 19F-NMR. In addition, for two purine derivatives, a reverse screening strategy based on ligand similarity (PharmMapper web server) resulted in a set of predicted protein target candidates. Interestingly, for both purines, the main potential target candidates belonged to key proteins involved within signaling pathways that are related to proliferation or survival of cancer cells. These proteins correspond mainly to enzymes and specifically kinases. To check if our purines could be ligands for two kinases involved in cancer, docking studies were performed. The results indicated that these purines fitted in the same cavity of crystalized inhibitors. Therefore, in this work we are developed new purine derivatives that could be good inhibitors of some kinases. In the experimental materials used by the author, we found tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Application of 87120-72-7)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Halogenation, in which one or more hydrogen atoms of an amine is replaced by a halogen atom, occurs with chlorine, bromine, and iodine, as well as with some other reagents, notably hypochlorous acid (HClO). With primary amines the reaction proceeds in two stages, producing N-chloro- and N,N-dichloro-amines, RNHCl and RNCl2, respectively. With tertiary amines, an alkyl group may be displaced by a halogen.Application of 87120-72-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Li, Xing-Zi; Jiang, Shi-You; Li, Guo-Qiang; Jiang, Qian-Ru; Li, Jue-Wan; Li, Chen-Chen; Han, Yu-Qin; Song, Bao-Liang; Ma, Xin-Ran; Qi, Wei; Qiu, Wen-Wei published an article in European Journal of Medicinal Chemistry. The title of the article was 《Synthesis of heterocyclic ring-fused analogs of HMG499 as novel degraders of HMG-CoA reductase that lower cholesterol》.Related Products of 87120-72-7 The author mentioned the following in the article:

HMG-CoA reductase (HMGCR) is the rate-limiting enzyme in cholesterol de novo biosynthesis and its degradation may bring therapeutic benefits for the treatment of cardiovascular disease (CVD) and nonalcoholic steatohepatitis (NASH). Before, we disclosed compound HMG499 (I) as a potent HMGCR degrader, which could be a promising agent for treating CVD, however its side-effect of promoting cholesterol accumulation in cells should be eliminated before progression. Herein, a series of novel heterocyclic ring-fused analogs of HMG499 were synthesized and investigated for their activities of stimulating HMGCR degradation using a HMGCR (TM1-8)-GFP reporting system. Among them, the most active compound 29 (II) (QH536) showed an EC50 of 0.22μM in promoting HMGCR degradation, which was about 2 times more potent than HMG499 (EC50 = 0.43μM). Interestingly, 29 was different from HMG499, it had no side-effect of inducing cholesterol accumulation in cells. Mechanistic studies disclosed that 29 could significantly decrease statin-induced accumulation of HMGCR protein via ubiquitination and degradation of HMGCR through ubiquitin-proteasome pathway and inhibit the cholesterol biosynthesis in cells. Therefore, these heterocyclic ring-fused analogs could be used as promising leads for the development of new types of agents against CVD. Furthermore, 29 also lowered cholesterol levels and suppressed TGFβ1-induced proliferation of LX-2 hepatic stellate cells in a dose-dependent manner. In particular, 29 not only decreased the NASH associated fibrotic mRNA and protein expression of α-SMA, COL1A1, TIMP1 and TGFβ1 but also suppressed cholesterol levels and inflammatory genes of TNF-α, IL-6 an IL-1β in RAW264.7 macrophage cells, indicating that 29 may bring therapeutic benefit to treat NASH. The results came from multiple reactions, including the reaction of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Related Products of 87120-72-7)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. Primary amines having a tertiary alkyl group (R3CNH2) are difficult to prepare with most methods but are made industrially by the Ritter reaction. In this method a tertiary alcohol reacts with hydrogen cyanide (HCN) in the presence of a concentrated strong acid; a formamide, RNH―CHO, is formed first, which then undergoes hydrolysis.Related Products of 87120-72-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Holman, Samuel D. L.; Wills, Alfie G.; Fazakerley, Neal J.; Poole, Darren L.; Coe, Diane M.; Berlouis, Leonard A.; Reid, Marc published an article in Chemistry – A European Journal. The title of the article was 《Electrochemical Synthesis of Isoxazolines: Method and Mechanism》.Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:

An electrochem. method for the green and practical synthesis of a broad range of substituted isoxazoline cores is presented. Both aryl and more challenging alkyl aldoximes are converted to the desired isoxazoline in an electrochem. enabled regio- and diastereoselective reaction with electron-deficient alkenes. Addnl., in-situ reaction monitoring methods compatible with electrochem. equipment have been developed in order to probe the reaction pathway. Supporting analyses from kinetic (time-course) modeling and d. functional theory support a stepwise, radical-mediated mechanism, and discounts hypothesised involvement of closed shell [3+2] cycloaddition pathways. The results came from multiple reactions, including the reaction of tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate)

tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7) belongs to anime. In organic chemistry, amines are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (NH3), wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group (these may respectively be called alkylamines and arylamines; amines in which both types of substituent are attached to one nitrogen atom may be called alkylarylamines).Application In Synthesis of tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Product Details of 1445-73-4In 2021 ,《High chemical stability anion exchange membrane based on poly(aryl piperidinium): Effect of monomer configuration on membrane properties》 appeared in International Journal of Hydrogen Energy. The author of the article were Long, Chuan; Wang, Zhihua; Zhu, Hong. The article conveys some information:

In recent years, ether-free polyaryl polymers prepared by superacid-catalyzed Friedel-Crafts polymerization have attracted great research interest in the development of anion exchange membranes(AEMs) due to their high alkali resistance and simple synthesis methods. However, the selection of monomers for high-performance polymer backbone and the relationship between polymer structure construction and properties need further investigated. Herein, a series of free-ether poly(aryl piperidinium) (PAP) with different polymer backbone steric construction were synthesized as stable anion exchange membranes. Meta-terphenyl, p-terphenyl and diphenyl-terphenyl copolymer were chosen as monomers to regulate the spatial arrangement of the polymer backbone, which tethered with stable piperidinium cation to improve the chem. stability. In addition, a multi-cation crosslinking strategy has been applied to improve ion conductivity and mech. stability of AEMs, and further compared with the performance of uncrosslinked AEMs. The properties of the resulting AEMs were investigated and correlated with their polymer structure. In particular, m-terphenyl based AEMs exhibited better dimensional stability and the highest hydroxide conductivity of 144.2 mS/cm at 80°C than other membranes, which can be attributed to their advantages of polymer backbone arrangement. Furthermore, the hydroxide conductivity of the prepared AEMs remains 80%-90% after treated by 2 M NaOH for 1600 h, exhibiting excellent alk. stability. The single cell test of m-PTP-20Q4 exhibits a maximum power d. of 239 mW/cm2 at 80°C. Hence, the results may guide the selection of polymer monomers to improve performance and alk. durability for anion exchange membranes.1-Methyl-4-piperidone(cas: 1445-73-4Product Details of 1445-73-4) was used in this study.

1-Methyl-4-piperidone(cas: 1445-73-4) is a member of piperidine. Piperidine-containing compounds are also frequently employed in synthesis as ligands or auxiliaries. Accordingly, many efforts have been devoted to the development of novel methods for the synthesis of these compounds over the years.Product Details of 1445-73-4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem