Tag: 200-300

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 Amines are formally derivatives of ammonia (NH3), wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group (these may respectively be called alkylamines and arylamines; amines in which both types of substituent are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

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,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,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

《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

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

Metwally, Kamel A.; Dukat, Malgorzata; Egan, Christina T.; Smith, Carol; DuPre, Ann; Gauthier, Colleen B.; Herrick-Davis, Katharine; Teitler, Milt; Glennon, Richard A. published their research in Journal of Medicinal Chemistry on December 3 ,1998. The article was titled 《Spiperone: Influence of Spiro Ring Substituents on 5-HT2A Serotonin Receptor Binding》.Recommanded Product: 136624-42-5 The article contains the following contents:

Spiperone is a widely used pharmacol. tool that acts as a potent dopamine D2, serotonin 5-HT1A, and serotonin 5-HT2A antagonist. Although spiperone also binds at 5-HT2C receptors, it is one of the very few agents that display some (∼1000-fold) binding selectivity for 5-HT2A vs. 5-HT2C receptors and, hence, might serve as a useful template for the development of novel 5-HT2A antagonists if the impact of its various substituent groups on binding was known. In the present investigation we focused on the 1,3,8-triazaspiro[4.5]decanone portion of spiperone and found that replacement of the N1-Ph group with a Me group only slightly decreased affinity for cloned rat 5-HT2A receptors. However, N1-Me derivatives displayed significantly reduced affinity for 5-HT1A, 5-HT2C, and dopamine D2 receptors. Several representative examples were shown to behave as 5-HT2 antagonists. As such, N1-alkyl analogs of spiperone may afford entry into a novel series of 5-HT2A-selective antagonists. The experimental process involved the reaction of 4-Amino-1-benzylpiperidine-4-carbonitrile(cas: 136624-42-5Recommanded Product: 136624-42-5)

4-Amino-1-benzylpiperidine-4-carbonitrile(cas: 136624-42-5) belongs to anime. Examples of direct uses of amines and their salts are as corrosion inhibitors in boilers and in lubricating oils (morpholine), as antioxidants for rubber and roofing asphalt (diarylamines), as stabilizers for cellulose nitrate explosives (diphenylamine), as protectants against damage from gamma radiation (diarylamines), as developers in photography (aromatic diamines), as flotation agents in mining, as anticling and waterproofing agents for textiles, as fabric softeners, in paper coating, and for solubilizing herbicides.Recommanded Product: 136624-42-5

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Synthetic Route of C13H16N2OOn September 30, 1983 ,《New antihypertensive agents. III. Synthesis and antihypertensive activity of some arylalkyl piperidines carrying a heterocycle at the 4-position》 was published in Chemical & Pharmaceutical Bulletin. The article was written by Obase, Hiroyuki; Nakamizo, Nobuhiro; Takai, Haruki; Teranishi, Masayuki; Kubo, Kazuhiro; Shuto, Katsuichi; Kasuya, Yutaka; Shigenobu, Koki; Hashikami, Makiko. The article contains the following contents:

Arylalkyl piperidines carrying a heterocycle at the 4-position of piperidine e.g. I, II, III, and IV were prepared and the hypotensive activities of the products examined Thus, 2-indolinone was treated with 1-benzyl-4-piperidinone followed by hydrogenolysis to give 4-(2-oxoindolin-3-yl)piperidine which was treated with 2-bromo-3′,4′-methylenedioxyacetophenone to give IV. Compound I had the highest hypotensive activity in anesthetized normotensive rats (-78 mmHg, 30 mg/kg, i.p.) and compound II showed the strongest hypotensive activity (-95 mmHg, 30 mg/kg p.o) in unanesthetized spontaneously hypertensive rats. Only III produced a considerable decrease in blood pressure in both animal models. In the experiment, the researchers used 3-(Piperidin-4-yl)indolin-2-one(cas: 72831-89-1Synthetic Route of C13H16N2O)

3-(Piperidin-4-yl)indolin-2-one(cas: 72831-89-1) belongs to piperidines. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions. Synthetic Route of C13H16N2O

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Thu, Zaw Min; Sun, Jian; Ji, Jingwen; He, Lili; Ji, Jinbo; Iqbal, Zafar; Myo, Ko Ko; Gao, Yuanyu; Zhai, Lijuan; Mu, Yangxiu; Tang, Dong; Vidari, Giovanni; Yang, Haikang; Yang, Zhixiang published an article in 2021. The article was titled 《Synthesis and antibacterial evaluation of new monobactams》, and you may find the article in Bioorganic & Medicinal Chemistry Letters.Application of 87120-72-7 The information in the text is summarized as follows:

Monobactams play an important role in antibiotic drug discovery. Based on the structural characteristics of aztreonam and its biol. targets, six new monobactam derivatives were synthesized and their in vitro antibacterial activities were investigated. Some compounds showed higher activities against tested gram-neg. bacteria than that of parent aztreonam. Monobactam I exhibited the most potent activities, with MIC ranging from 0.25 to 2μg/mL against most bacteria. The experimental part of the paper was very detailed, including the reaction process of 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. Many important products require amines as part of their syntheses. Methylamine is utilized in the production of the analgesic meperidine (trade name Demerol) and the photographic developer Metol (trademark), and dimethylamine is used in the synthesis of the antihistamine diphenhydramine (trade name Benadryl), the solvent dimethylformamide (DMF), and the rocket propellant 1,1-dimethylhydrazine. The synthesis of the insect repellent N,N-diethyl-m-toluamide (DEET) incorporates diethylamine while that of the synthetic fibre Kevlar requires aromatic amines.Application of 87120-72-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Luo, Guoshun; Lin, Xin; Li, Zhenbang; Xiao, Maoxu; Li, Xinyu; Zhang, Dayong; Xiang, Hua published an article in 2021. The article was titled 《Structure-guided modification of isoxazole-type FXR agonists: Identification of a potent and orally bioavailable FXR modulator》, and you may find the article in European Journal of Medicinal Chemistry.Name: tert-Butyl 4-hydroxypiperidine-1-carboxylate The information in the text is summarized as follows:

Farnesoid X receptor (FXR) agonists are emerging as potential therapeutics for the treatment of various metabolic diseases, as they display multiple effects on bile acid, lipid, and glucose homeostasis. Although the steroidal obeticholic acid, a full FXR agonist, was recently approved, several side effects probably due to insufficient pharmacol. selectivity impede its further clin. application. Activating FXR in a partial manner is therefore crucial in the development of novel FXR modulators. Our efforts focusing on isoxazole-type FXR agonists, common nonsteroidal agonists for FXR, led to the discovery a series of novel FXR agonists bearing aryl urea moieties through structural simplification of LJN452 (phase 2). Encouragingly, compound I was discovered as a potent FXR agonist which exhibited similar FXR agonism potency but lower maximum efficacy compared to full agonists GW4064 and LJN452 in cell-based FXR transactivation assay. Extensive in vitro evaluation further confirmed partial efficacy of I in cellular FXR-dependent gene modulation, and revealed its lipid-reducing activity. More importantly, orally administration of I in mice exhibited desirable pharmacokinetic characters resulting in promising in vivo FXR agonistic activity. The results came from multiple reactions, including the reaction of tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Name: tert-Butyl 4-hydroxypiperidine-1-carboxylate)

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.Name: tert-Butyl 4-hydroxypiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem