Heterocyclic Building Blocks-piperidine

《Amine-Responsive Disassembly of AuI-CuI Double Salts for Oxidative Carbonylation》 was published in Angewandte Chemie, International Edition in 2020. These research results belong to Cao, Yanwei; Yang, Jian-Gong; Deng, Yi; Wang, Shengchun; Liu, Qi; Shen, Chaoren; Lu, Wei; Che, Chi-Ming; Chen, Yong; He, Lin. Application In Synthesis of tert-Butyl 4-hydroxypiperidine-1-carboxylate The article mentions the following:

A sensitive amine-responsive disassembly of self-assembled AuI-CuI double salts was observed and its use for the synergistic catalysis was enlightened. Study of the disassembly of [Au(NHC)2][CuI2] revealed the contribution of Cu-assisted ligand exchange of N-heterocyclic carbene (NHC) by amine in [Au(NHC)2]+ and the capacity of [CuI2]- on the oxidative step. By integrating the implicative information coded in the responsive behavior and inherent catalytic functions of d10 metal complexes, a catalyst for the oxidative carbonylation of amines was developed. The advantages of this method were clearly reflected on mild reaction conditions and the significantly expanded scope (51 examples); both primary and steric secondary amines can be employed as substrates. The cooperative reactivity from Au and Cu centers, as an indispensable prerequisite for the excellent catalytic performance, was validated in the synthesis of (un)sym. ureas and carbamates. The results came from multiple reactions, including the reaction of tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Application In Synthesis of 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.Application In Synthesis of tert-Butyl 4-hydroxypiperidine-1-carboxylate

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

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

Reference of 2-(Piperidin-4-yl)ethanolIn 2022 ,《Discovery and structure-based design of a new series of potent and selective PPARδ agonists utilizing a virtual screening method》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Kato, Terukazu; Ohara, Takafumi; Suzuki, Naoyuki; Muto, Susumu; Tokuyama, Ryukou; Mizutani, Miho; Fukasawa, Hiroshi; Matsumura, Ken-ichi; Itai, Akiko. The article conveys some information:

Novel PPARδ agonists, 2-(1-piperidinyl)-1,3-benzothiazole derivatives were discovered by our proprietary docking-based virtual screening technique. Compound 1 as the initial hit was effectively modified to acquire PPARδ agonist activity, resulting in the discovery of compound 12 with high agonistic potency for PPARδ and selectivity over PPARα and PPARγ. Compound 12 also had good ADME profiles and showed in vivo efficacy as a lead. In the part of experimental materials, we found many familiar compounds, such as 2-(Piperidin-4-yl)ethanol(cas: 622-26-4Reference of 2-(Piperidin-4-yl)ethanol)

2-(Piperidin-4-yl)ethanol(cas: 622-26-4) have been used as an intermediate in the synthetic preparation of cellular-active allosteric inhibitors of FAKReference of 2-(Piperidin-4-yl)ethanol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

HPLC of Formula: 1445-73-4In 2019 ,《Protein labelling and albumin binding characteristics of the near-IR Cy7 fluorophore, QuatCy》 appeared in Organic & Biomolecular Chemistry. The author of the article were Thavornpradit, Sopida; Usama, Syed Muhammad; Lin, Chen-Ming; Burgess, Kevin. The article conveys some information:

Free cysteine residues react with QuatCy 1, by simply mixing the protein and dye in aqueous buffer at 37°C. Another dye, MHI-148, can be used for a similar labeling protocol, but QuatCy reacts faster with all proteins studied, except albumin; it emerges here that this is because MHI-148 instantly forms of a non-covalent complex with albumin, but QuatCy does not. Labeling with QuatCy has advantages insofar as it is over five times brighter, and much more photostable, than MHI-148, and combination labeling with this dye pair will allow multiplexing in the near-IR region. In the experimental materials used by the author, we found 1-Methyl-4-piperidone(cas: 1445-73-4HPLC of Formula: 1445-73-4)

1-Methyl-4-piperidone(cas: 1445-73-4) is a member of piperidine. Piperidine is a key saturated heterocyclic scaffold found in several of the top-selling small molecule pharmaceuticals and natural alkaloids, with a diverse range of biological activities. Hence, continuous efforts have been made to develop convenient methods to prepare piperidine derivatives.HPLC of Formula: 1445-73-4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Formula: C10H19NO3In 2019 ,《Discovery of (R)-5-((5-(1-methyl-1H-pyrazol-4-yl)-4-(methylamino)pyrimidin-2-yl)amino)-3-(piperidin-3-yloxy)picolinonitrile, a novel CHK1 inhibitor for hematologic malignancies》 appeared in European Journal of Medicinal Chemistry. The author of the article were Tong, Lexian; Song, Pinrao; Jiang, Kailong; Xu, Lei; Jin, Tingting; Wang, Peipei; Hu, Xiaobei; Fang, Sui; Gao, Anhui; Zhou, Yubo; Liu, Tao; Li, Jia; Hu, Yongzhou. The article conveys some information:

Through virtual screening, we identified the lead compound MCL1020, which exhibited modest CHK1 inhibitory activity. Then a series of 5-(pyrimidin-2-ylamino)picolinonitrile derivatives as CHK1 inhibitors were discovered by further rational optimization. One promising mol., I, whose potency was one of the best, had an IC50 of 0.4 nM with remarkable selectivity (>4300-fold CHK1 vs. CHK2). Compound I effectively inhibited the growth of malignant hematopathy cell lines especially Z-138 (IC50: 0.013 μM) and displayed low affinity for hERG (IC50 > 40 μM). Moreover, I significantly suppressed the tumor growth in Z-138 cell inoculated xenograft model (20 mg/kg I.V., TGI = 90.29%) as a single agent with body weight unaffected. Taken together, our data demonstrated compound I could be a promising drug candidate for the treatment of hematol. malignancies. The results came from multiple reactions, including the reaction of tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Formula: C10H19NO3)

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.Formula: C10H19NO3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Application of 87120-72-7In 2020 ,《Design, synthesis, biological evaluation and molecular docking study of novel thieno[3,2-d]pyrimidine derivatives as potent FAK inhibitors》 was published in European Journal of Medicinal Chemistry. The article was written by Wang, Ruifeng; Yu, Sijia; Zhao, Xiangxin; Chen, Yixuan; Yang, Bowen; Wu, Tianxiao; Hao, Chenzhou; Zhao, Dongmei; Cheng, Maosheng. The article contains the following contents:

A series of 2,7-disubstituted thieno[3,2-d]pyrimidine derivatives I [R1 = 2-methoxy, 3-acetyl, 3-methylsulfonyl, etc.], II [R2 = methylcarbamoyl, piperidine-3-carbonylamino, diethoxyphosphorylmethyl, etc.], III [R3 = H, Me, ethoxy, etc.; R4 = H, fluoro, methyl; R5 = H, fluoro] and IV [R6 = pyrrolidin-3-yl, tetrahydro-2H-pyran-4-yl, piperidin-3-ylmethyl, etc.] were synthesized and evaluated as novel focal adhesion kinase (FAK) inhibitors. The novel 2,7-disubstituted thieno[3,2-d]pyrimidine scaffold was designed as a new kinase inhibitor platform that mimics the bioactive conformation of the well-known diaminopyrimidine motif. Most of the compounds potently suppressed the enzymic activities of FAK and potently inhibited the proliferation of U-87MG, A-549 and MDA-MB-231 cancer cell lines. Among these derivatives, the optimized compound III [R3 = R5 = H, R4 = fluoro] potently inhibited the enzyme (IC50 = 28.2 nM) and displayed stronger potency than TAE-226 in U-87MG, A-549 and MDA-MB-231 cells, with IC50 values of 0.16, 0.27, and 0.19μM, resp. Compound III [R3 = R5 = H, R4 = fluoro] also exhibited relatively less cytotoxicity (IC50 = 3.32μM) toward a normal human cell line, HK2. According to the flow cytometry results, compound III [R3 = R5 = H, R4 = fluoro] induced the apoptosis of MDA-MB-231 cells in a dose-dependent manner and effectively arrested MDA-MB-231 cells in G0/G1 phase. Further investigations revealed that compound III [R3 = R5 = H, R4 = fluoro] potently suppressed the migration of MDA-MB-231 cells. Collectively, these data support the further development of compound III [R3 = R5 = H, R4 = fluoro] as a lead compound for FAK-targeted anticancer drug discovery. 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. Amines have a free lone pair with which they can coordinate to metal centers. Amine–metal bonds are weaker because amines are incapable of backbonding, but they are still important for sensing applications.While stronger than hydrogen bonds, amine–metal bonds are still weaker than both covalent and ionic bonds.Application of 87120-72-7

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Safety of Piperidine-4-carboxamideOn October 19, 2020 ,《Biocarbon Supported Nanoscale Ruthenium Oxide-Based Catalyst for Clean Hydrogenation of Arenes and Heteroarenes》 was published in ACS Sustainable Chemistry & Engineering. The article was written by Kumar, Adarsh; Goyal, Vishakha; Sarki, Naina; Singh, Baint; Ray, Anjan; Bhaskar, Thallada; Bordoloi, Ankur; Narani, Anand; Natte, Kishore. The article contains the following contents:

Despite considerable achievements in the hydrogenation of aromatic hydrocarbons over the past few years, the ability to hydrogenate arene or heteroarene rings in a highly selective manner in the presence of other reducible sites or without harming the remaining mol. structure has long been a major challenge. Such chemoselectivity and functional group tolerance is highly desirable for enabling direct access to key building blocks of polymers and pharmaceutical agents. For achieving such high selectivity, the development of suitable catalysts is of central importance. Herein, we report a convenient method for the scalable preparation of ruthenium oxide (RuO2) nanoparticles supported on pine needle char (PNC) by simple impregnation of ruthenium salt on unactivated PNC, a solid byproduct (biochar) obtained in the slow pyrolysis of biomass pine needles. The resulting RuO2-based nanocatalyst (RuO2@PNC) exhibited remarkable activity and high selectivity for the hydrogenation of more than 50 challenging arenes and heteroarenes, including biomass-derived aromatic compounds (e.g., 4-n-propylphenol, furfuryl alc., and 2-Me furan). The synthetic value of this transformation is showcased for the hydrogenation of arene mixture present in petroleum refineries or coal tars as well as biomass-derived oils (bio-oils) with enriched furfural, ether, and phenol derivatives Under optimized conditions, the performance of this new catalyst was compared with state-of-the-art com. catalysts such as Ru/C, Pd/C, and Raney nickel and found that RuO2@PNC is more superior and selective. Furthermore, the catalyst is easily recovered and reused up to four cycles. Biocarbon supported RuO2-based catalyst exhibited remarkable activity and selectivity for clean hydrogenation of arenes and heteroarenes. After reading the article, we found that the author used Piperidine-4-carboxamide(cas: 39546-32-2Safety of Piperidine-4-carboxamide)

Piperidine-4-carboxamide(cas: 39546-32-2) belongs to anime. Hydrogen peroxide (H2O2) and peroxy acids generally add an oxygen atom to the nitrogen of amines. With primary amines, this step is normally followed by further oxidation, leading to nitroso compounds, RNO, or nitro compounds, RNO2. Secondary amines are converted to hydroxylamines, R2NOH, and tertiary amines to amine oxides, R3NO.Safety of Piperidine-4-carboxamide

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Reference of Piperidine-4-carboxamideOn March 15, 2019, de Andrade, Peterson; Mantoani, Susimaire P.; Goncalves Nunes, Paulo Sergio; Magadan, Carlos Roca; Perez, Concepcion; Xavier, Danilo Jordao; Hojo, Elza Tiemi Sakamoto; Campillo, Nuria E.; Martinez, Ana; Carvalho, Ivone published an article in Bioorganic & Medicinal Chemistry. The article was 《Highly potent and selective aryl-1,2,3-triazolyl benzylpiperidine inhibitors toward butyrylcholinesterase in Alzheimer’s disease》. The article mentions the following:

Acetylcholinesterase (AChE) is the key enzyme targeted in Alzheimer’s disease (AD) therapy, nevertheless butyrylcholinesterase (BuChE) has been drawing attention due to its role in the disease progression. Thus, we aimed to synthesize novel cholinesterases inhibitors considering structural differences in their peripheral site, exploiting a moiety replacement approach based on the potent and selective hAChE drug donepezil. Hence, two small series of N-benzylpiperidine based compounds have successfully been synthesized as novel potent and selective hBuChE inhibitors. The most promising compounds (9(I) and 11(II)) were not cytotoxic and their kinetic study accounted for dual binding site mode of interaction, which is in agreement with further docking and mol. dynamics studies. Therefore, this study demonstrates how our strategy enabled the discovery of novel promising and privileged structures. Remarkably, II proved to be one of the most potent (0.17 nM) and selective (>58,000-fold) hBuChE inhibitor ever reported. In the experiment, the researchers used many compounds, for example, Piperidine-4-carboxamide(cas: 39546-32-2Reference of Piperidine-4-carboxamide)

Piperidine-4-carboxamide(cas: 39546-32-2) belongs to anime. Amines characteristically form salts with acids; a hydrogen ion, H+, adds to the nitrogen. With the strong mineral acids (e.g., H2SO4, HNO3, and HCl), the reaction is vigorous. Salt formation is instantly reversed by strong bases such as NaOH. Neutral electrophiles (compounds attracted to regions of negative charge) also react with amines; alkyl halides (R′X) and analogous alkylating agents are important examples of electrophilic reagents.Reference of Piperidine-4-carboxamide

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Name: Piperidine-4-carboxamideOn October 15, 2020 ,《Design, synthesis and bioevaluation of novel substituted triazines as potential dual PI3K/mTOR inhibitors》 was published in European Journal of Medicinal Chemistry. The article was written by Wu, Ting-Ting; Guo, Qing-Qing; Chen, Zi-Li; Wang, Li-Li; Du, Yao; Chen, Rui; Mao, Yuan-Hu; Yang, Sheng-Gang; Huang, Jing; Wang, Jian-Ta; Wang, Ling; Tang, Lei; Zhang, Ji-Quan. The article contains the following contents:

A series of novel substituted triazines bearing a benzimidazole scaffold I [R = morpholino, 4-methylpiperazin-1-yl, ((1S)-2-amino-1-methyl-2-oxo-ethyl)amino, etc.] were designed and synthesized based on the structures of known anti-cancer agents, namely gedatolisib and alpelisib. All the target compounds were screened for inhibitory activity against PI3Kα and mTOR kinases. Notably, most analogs exhibited IC50 in the nanomolar range. Investigation of the isoenzyme selectivity indicated that the compounds exhibited remarkable inhibitory activity against PI3Kδ, especially compound I [R = 4-carbamoyl-1-piperidyl] showed an IC50 value of 2.3 nM for PI3Kδ and moderate δ-isoenzyme selectivity over other class I PI3K isoforms and mTOR (with IC50 values of 14.6, 34.0, 849.0 and 15.4 nM for PI3Kα, β, γ and mTOR, resp.). An in vitro MTT assay was conducted to assess the antiproliferative and cytotoxic effects of the prepared analogs. It was revealed that the compounds displayed significant inhibitory activities against the HCT116 human colon cancer cell line. Compound I [R = morpholino] showed 4.7-fold higher potency than the pos. control gedatolisib (0.3 vs. 1.4μM, IC50 values). Phosphoblot studies demonstrated that I [R = morpholino, (2R)-2-carbamoylpyrrolidin-1-yl] could significantly suppress the PI3K/Akt/mTOR signaling pathway at 10μM. Moreover, analogs I [R = morpholino, (2S)-2-carbamoylpyrrolidin-1-yl, (2R)-2-carbamoylpyrrolidin-1-yl] displayed better stability in artificial gastric fluids than gedatolisib, while I [R = morpholino] was indicated not very stable in rat liver microsomes, and may occur phase I metabolic transformations. After reading the article, we found that the author used Piperidine-4-carboxamide(cas: 39546-32-2Name: Piperidine-4-carboxamide)

Piperidine-4-carboxamide(cas: 39546-32-2) belongs to anime. Hydrogen peroxide (H2O2) and peroxy acids generally add an oxygen atom to the nitrogen of amines. With primary amines, this step is normally followed by further oxidation, leading to nitroso compounds, RNO, or nitro compounds, RNO2. Secondary amines are converted to hydroxylamines, R2NOH, and tertiary amines to amine oxides, R3NO.Name: Piperidine-4-carboxamide

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem