Category: piperidines

《Molecular Tuning of a Vitamin E-Scaffold pH-Sensitive and Reductive Cleavable Lipid-like Material for Accelerated in Vivo Hepatic siRNA Delivery》 was written by Akita, Hidetaka; Noguchi, Yuki; Hatakeyama, Hiroto; Sato, Yusuke; Tange, Kota; Nakai, Yuta; Harashima, Hideyoshi. Recommanded Product: 2-(Piperidin-4-yl)ethanolThis research focused onvitamin E pH reductive cleavable lipid liver siRNA targeting; drug delivery system; liposomal nanoparticle; liver; siRNA. The article conveys some information:

A lipid nanoparticle (LNP) composed of a series of SS-cleavable and pH-activated lipid-like materials (ssPalm) was previously developed as a platform of a gene delivery system. A tertiary amine and disulfide bonding were employed to destabilize the endosomal membrane and for intracellular collapse. We report herein on the development of a hepatocyte-targeting siRNA carrier by the mol. tuning of the hydrophobic scaffold, and tertiary amine structures. The gene knockdown activity against a hepatocyte-specific marker (factor VII: FVII) was improved when a more fat-soluble vitamin (vitamin E) was employed as a hydrophobic scaffold. Moreover, to allow the tertiary amines to accept protons by sensing a slight change in endosomal acidification, its structural flexibility was minimized by fixing it in a piperidine structure, and the distance between the surface of the particle to the ternary amine was increased. As a result, the pKa value was increased to the approx. 6.18 depending on its distance, while the pKa reached plateau when the tertiary amine was linked by an excess number of linear carbon chains. The pH-dependent membrane destabilization activity, as assessed by a hemolysis assay, was increased in parallel with the pKa value. Moreover, the gene knockdown activity was improved in parallel with hemolytic activity. Finally, further optimization of the lipid/siRNA ratio, and the use of chem. (2′-fluoro) modified siRNA synergistically improved the gene knockdown efficacy to an ED (ED50) of 0.035 mg/kg. The developed ssPalm represents a promising platform for use as a hepatocyte-targeting siRNA carrier. The results came from multiple reactions, including the reaction of 2-(Piperidin-4-yl)ethanol(cas: 622-26-4Recommanded Product: 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 FAKRecommanded Product: 2-(Piperidin-4-yl)ethanol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

《Diffusion of reduced arecoline and arecaidine through human vaginal and buccal mucosa》 was written by Van der Bijl, P.; Van Eyk, A. D.; Van Wyk, C. W.; Stander, I. A.. Category: piperidines And the article was included in Journal of Oral Pathology & Medicine on April 30 ,2001. The article conveys some information:

Because alkaloids from areca nut, arecoline and arecaidine, have been implicated in the development of oral submucous fibrosis, the authors determined their diffusion kinetics through human buccal and vaginal mucosa. Four clin. healthy vaginal mucosa specimens (mean patient age ± standard deviation: 47±15 yr; age range: 31-60 yr) and 4 buccal mucosa specimens from 2 male patients and 2 female patients (mean patient age ± standard deviation: 31±9 yr; age range: 17-53 yr) were obtained during surgery. In vitro flux rates of reduced arecoline and arecaidine (r-arecoline and r-arecaidine) were determined by use of a flow-through diffusion apparatus Anal. of variance, a Duncan multiple range test, and an unpaired t-test were used to determine steady state kinetics and flux differences over time intervals. Although statistically significant differences were observed between flux values for both alkaloids and tissues at certain time points, these were not considered to be of biol. (clin.) significance. However, the flux rates across both mucosa of r-arecoline were significantly higher statistically than those of r-arecaidine. The findings demonstrated the differences in the diffusion kinetics between r-arecoline and r-arecaidine across human buccal and vaginal mucosa, an observation that could be explained in terms of their ionization characteristics. Addnl., the results obtained further support the hypothesis that human vaginal mucosa can be used as a model for buccal mucosa in studies of permeability to various chem. compounds The results came from multiple reactions, including the reaction of Methyl 1-methylpiperidine-3-carboxylate(cas: 1690-72-8Category: piperidines)

Methyl 1-methylpiperidine-3-carboxylate(cas: 1690-72-8) 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.Category: piperidines

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

COA of Formula: C7H15NOIn 2013 ,《Structure-based discovery of cellular-active allosteric inhibitors of FAK》 appeared in Bioorganic & Medicinal Chemistry Letters. The author of the article were Tomita, Naoki; Hayashi, Yoko; Suzuki, Shinkichi; Oomori, Yoshimasa; Aramaki, Yoshio; Matsushita, Yoshihiro; Iwatani, Misa; Iwata, Hidehisa; Okabe, Atsutoshi; Awazu, Yoshiko; Isono, Osamu; Skene, Robert J.; Hosfield, David J.; Miki, Hiroshi; Kawamoto, Tomohiro; Hori, Akira; Baba, Atsuo. The article conveys some information:

In order to develop potent and selective focal adhesion kinase (FAK) inhibitors, synthetic studies on pyrazolo[4,3-c][2,1]benzothiazines targeted for the FAK allosteric site were carried out. Based on the X-ray structural anal. of the co-crystal of the lead compound, 8-(4-ethylphenyl)-5-methyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazine 4,4-dioxide 1 with FAK, we designed and prepared 1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin derivatives which selectively inhibited kinase activity of FAK without affecting seven other kinases. The optimized compound, N-(4-tert-butylbenzyl)-1,5-dimethyl-1,5-dihydropyrazolo[4,3-c][2,1]benzothiazin-8-amine 4,4-dioxide 30 possessed significant FAK kinase inhibitory activities both in cell-free (IC50 = 0.64 μM) and in cellular assays (IC50 = 7.1 μM). These results clearly demonstrated a potential of FAK allosteric inhibitors as antitumor agents. The experimental part of the paper was very detailed, including the reaction process of 2-(Piperidin-4-yl)ethanol(cas: 622-26-4COA of Formula: C7H15NO)

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 FAKCOA of Formula: C7H15NO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Lu, Shaoyong; Fu, Zhong; Li, Fu; Weng, Kangkang; Zhou, Likuan; Zhang, Lipeng; Yang, Yuchen; Qiu, Hengwei; Liu, Dan; Qing, Wenyue; Ding, He; Sheng, Xing; Chen, Menglu; Tang, Xin; Duan, Lian; Liu, Wenyong; Wu, Longjia; Yang, Yixing; Zhang, Hao; Li, Jinghong published an article in Angewandte Chemie, International Edition. The title of the article was 《Beyond a Linker: The Role of Photochemistry of Crosslinkers in the Direct Optical Patterning of Colloidal Nanocrystals》.Electric Literature of C6H11NO The author mentioned the following in the article:

Surface chem. mediated direct optical patterning represents an emerging strategy for incorporating colloidal nanocrystals (NCs) in integrated optoelectronic platforms including displays and image sensors. However, the role of photochem. of crosslinkers and other photoactive species in patterning remains elusive. Here we show the design of nitrene- and carbene-based photocrosslinkers can strongly affect the patterning capabilities and photophys. properties of NCs, especially quantum dots (QDs). Their role beyond phys. linkers stems from structure-dictated electronic configuration, energy alignment and associated reaction kinetics and thermodn. Patterned QD layers with designed carbene-based crosslinkers fully preserve their photoluminescent and electroluminescent properties. Patterned light emitting diodes (QLEDs) show a maximum external quantum efficiency of ∼12 % and lifetime over 4800 h, among the highest for reported patterned QLEDs. These results would guide the rational design of photoactive species in NC patterning and create new possibilities in the monolithic integration of NCs in high-performance device platforms. The experimental part of the paper was very detailed, including the reaction process of 1-Methyl-4-piperidone(cas: 1445-73-4Electric Literature of C6H11NO)

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.Electric Literature of C6H11NO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Safety of 2-(Piperidin-4-yl)ethanolIn 2014 ,《Synthesis and in vitro evaluation of tetrahydroisoquinolines with pendent aromatics as sigma-2 (σ2) selective ligands》 was published in Organic & Biomolecular Chemistry. The article was written by Ashford, Mark E.; Nguyen, Vu H.; Greguric, Ivan; Pham, Tien Q.; Keller, Paul A.; Katsifis, Andrew. The article contains the following contents:

5-Bromo-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl]-2,3-dimethoxybenzamide 1 is a potent and selective σ2 receptor ligand suitable for further development. A series of new analogs, incorporating a variety of isoquinoline and carboxylic acid moieties,e.g. I [R = 2-indolyl, styryl, 1-naphthyl, etc.], linked together with either a linear or cyclic amine spacer have been synthesized and assessed for their σ1/σ2 binding affinity and selectivity. Compounds with a rigid piperidine spacer gave Ki values for the σ2 receptor between 8.7-845 nM. Changing the configuration of the methoxy groups on the isoquinoline moiety resulted in mols. with σ2Ki values of 4.4-133 nM whereas varying the length and flexibility of the carbon spaces gave σ2Ki values 0.88-15.0 nM, some of the most active, selective σ2 ligands to date. Thus, the flexibility and length of the carbon linker and the carboxylic acid moiety are confirmed to be key to the exceptional binding affinity and selectivity for this active series. Addnl., the incorporation of a halogen on selected carboxylic acid moieties provided a convenient strategy for the introduction of a radiohalogen for applications in pharmacol. and imaging studies. In the experiment, the researchers used 2-(Piperidin-4-yl)ethanol(cas: 622-26-4Safety 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 FAKSafety of 2-(Piperidin-4-yl)ethanol

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Cao, Yu; Tu, Yutong; Fu, Liping; Yu, Qian; Gao, Lixin; Zhang, Mengmeng; Zeng, Linghui; Zhang, Chong; Shao, Jiaan; Zhu, Huajian; Zhou, Yubo; Li, Jia; Zhang, Jiankang published an article in European Journal of Medicinal Chemistry. The title of the article was 《Metabolism guided optimization of peptidomimetics as non-covalent proteasome inhibitors for cancer treatment》.Name: tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:

A series of novel non-covalent peptidomimetic proteasome inhibitors possessing bulky group at the C-terminus and N-alkylation at the N-terminus were designed with the aim to increase metabolic stabilities in vivo. All the target compounds were screened for their inhibitory activities against human 20S proteasome, and most analogs exhibited notable potency compared with the pos. control bortezomib with IC50 values lower than 10 nM, which also displayed potent cytotoxic activities against multiple myeloma (MM) cell lines and human acute myeloid leukemia (AML) cells. Furthermore, whole blood stability and in vivo proteasome inhibitory activity experiments of selected compounds were conducted for further evaluation, and the representative compound 43 (IC50 = 8.39 ± 2.32 nM, RPMI-8226: IC50 = 15.290 ± 2.281 nM, MM-1S: IC50 = 9.067 ± 3.103 nM, MV-4-11: IC50 = 2.464 ± 0.713 nM) revealed a half-life extension of greater than 9-fold (329.21 min VS 36.79 min) and potent proteasome inhibitory activity in vivo. The pos. results confirmed the reliability of the metabolism guided optimization strategy, and the analogs discovered are potential leads for exploring new anti-MM drugs. In the part of experimental materials, we found many familiar compounds, such as 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. 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.Name: tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Huang, Mingming; Hu, Jiefeng; Krummenacher, Ivo; Friedrich, Alexandra; Braunschweig, Holger; Westcott, Stephen A.; Radius, Udo; Marder, Todd B. published an article in Chemistry – A European Journal. The title of the article was 《Base-Mediated Radical Borylation of Alkyl Sulfones》.Reference of tert-Butyl 4-hydroxypiperidine-1-carboxylate The author mentioned the following in the article:

A practical and direct method was developed for the production of versatile alkyl boronate esters via transition metal-free borylation of primary and secondary alkyl sulfones. The key to the success of the strategy is the use of bis(neopentyl glycolato) diboron (B2neop2), with a stoichiometric amount of base as a promoter. The practicality and industrial potential of this protocol are highlighted by its wide functional group tolerance, the late-stage modification of complex compounds, no need for further transesterification, and operational simplicity. Radical clock, radical trap experiments, and EPR studies were conducted which show that the borylation process involves radical intermediates. In the experiment, the researchers used tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Reference 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.Reference of tert-Butyl 4-hydroxypiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Zhang, Zhuming; Connolly, Peter J.; Trabalon Escolar, Luis; Rocaboy, Christian; Pande, Vineet; Meerpoel, Lieven; Lim, Heng-Keang; Branch, Jonathan R.; Ondrus, Janine; Hickson, Ian; Bush, Tammy L.; Bischoff, James R.; Bignan, Gilles published their research in ACS Medicinal Chemistry Letters in 2021. The article was titled 《Spirocyclic Thiohydantoin Antagonists of F877L and Wild-Type Androgen Receptor for Castration-Resistant Prostate Cancer》.Formula: C10H19NO3 The article contains the following contents:

Androgen receptor (AR) transcriptional reactivation plays a key role in the development and progression of lethal castration-resistant prostate cancer (CRPC). Recurrent alterations in the AR enable persistent AR pathway signaling and drive resistance to the treatment of second-generation antiandrogens. AR F877L, a point mutation in the ligand binding domain of the AR, was identified in patients who acquired resistance to enzalutamide or apalutamide. In parallel to our previous structure-activity relationship (SAR) studies of compound 4 (JNJ-pan-AR) and clin. stage compound 5 (JNJ-63576253), we discovered addnl. AR antagonists that provide opportunities for future development. Here we report a highly potent series of spirocyclic thiohydantoins as AR antagonists for the treatment of the F877L mutant and wild-type CRPC. A chirally pure enantiomer,(R)-29 (I) is a full antagonist against AR F877L. In the part of experimental materials, we found many familiar compounds, such as 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

《Novel pleuromutilin derivatives with substituted 6-methylpyrimidine: Design, synthesis and antibacterial evaluation》 was written by Fan, Yuan; Liu, Yu; Wang, Hao; Shi, Tao; Cheng, Feng; Hao, Baocheng; Yi, Yunpeng; Shang, Ruofeng. SDS of cas: 622-26-4 And the article was included in European Journal of Medicinal Chemistry in 2020. The article conveys some information:

A series of novel pleuromutilin derivatives with substituted 6-methylpyrimidine moieties was designed, synthesized, and evaluated for their antibacterial activities. Most of the tested compounds exhibited potent antibacterial activities against Staphylococcus aureus ATCC 25923 (S. aureus-25923), methicillin-resistant Staphylococcus epidermidis ATCC 51625 (MRSE-51625), methicillin-resistant Staphylococcus aureus BNCC 337371 (MRSA-337371), Streptococcus dysgalactiae (S. dysgalactiae) and Streptococcus agalactiae (S. agalactiae). Compounds I (NR1R2 = pyrrolidino, morpholino) were the most active and displayed bacteriostatic activities against MRSA. In vivo mouse systemic infection experiment showed that I (NR1R2 = pyrrolidino) significantly improved the survival rate of mice (ED50 = 18.02 mg/kg), reduced the bacterial load and alleviated the pathol. changes in the lungs of the affected mice. In the part of experimental materials, we found many familiar compounds, such as 2-(Piperidin-4-yl)ethanol(cas: 622-26-4SDS of cas: 622-26-4)

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 FAKSDS of cas: 622-26-4

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

The author of 《Preclinical efficacy of a novel dual PI3K/mTOR inhibitor, CMG002, alone and in combination with sorafenib in hepatocellular carcinoma》 were Kim, Mi Na; Lee, Seung Min; Kim, Jin Sung; Hwang, Seong Gyu. And the article was published in Cancer Chemotherapy and Pharmacology in 2019. Synthetic Route of C10H20N2O2 The author mentioned the following in the article:

Sorafenib has been the only first systemic drug that improves survival of patients with advanced hepatocellular carcinoma (HCC). However, because the response rate of sorafenib is relatively low, novel therapeutic strategies are needed to improve survival in patients with HCC. This study investigated the effect of CMG002 alone and in combination with sorafenib on HCC in vitro and vivo. The effect of a newly developed dual PI3K/mTOR inhibitor, CMG002, on the proliferation of Huh-7 and HepG2 HCC cells was investigated using the MTT assay. Western blotting was performed to assess phosphorylation of the key enzymes in the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. HepG2 cells were inoculated into mice, which were treated with vehicle, sorafenib, CMG002, and their combinations. Tumor cell proliferation and tumor angiogenesis were evaluated by immunohistochem. anal. of Ki-67 and CD31, resp. Tumor cell apoptosis was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Levels of key enzymes in the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways were evaluated by western blot anal. The combination of sorafenib and CMG002 additively inhibited Huh-7 and HepG2 cell proliferation compared to single-agent treatment. Sorafenib and CMG002 as single agents differentially inhibited or activated key enzymes in the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. The combination of sorafenib and CMG002 inhibited all key enzymes in the two pathways. Treatment with CMG002 for 4 wk alone and in combination with sorafenib strongly inhibited tumor growth. CMG002 inhibited HCC cell proliferation, induced apoptosis, and decreased tumor angiogenesis. Furthermore, these effects were enhanced when CMG002 was combined with sorafenib. The combination of CMG002 and sorafenib significantly inhibited HCC cell proliferation and tumorigenesis by inhibiting the Ras/Raf/MAPK and PI3K/AKT/mTOR pathways. These findings suggest that CMG002 to be a potential novel candidate treatment for HCC. After reading the article, we found that the author used tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Synthetic Route of C10H20N2O2)

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.Synthetic Route of C10H20N2O2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem