Category: piperidines

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

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

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

《Design, Synthesis, and Fungicidal Activities of Novel Piperidyl Thiazole Derivatives Containing Oxime Ether or Oxime Ester Moieties》 was written by Bian, Qiang; Zhao, Rui-Qi; Peng, Xing-Jie; Gao, Li-Jie; Zhou, Guo-Na; Yu, Shu-Jing; Zhao, Wei-Guang. Application of 39546-32-2 And the article was included in Journal of Agricultural and Food Chemistry on April 7 ,2021. The article conveys some information:

To explore the influence of the positions of the two nitrogen atoms on the thiazole ring and the isoxazoline ring on the activity, a series of novel piperidyl thiazole derivatives containing oxime ether and oxime ester moieties with two nitrogen atoms on the same or opposite sides have been designed, synthesized, and first evaluated for their fungicidal activities against Phytophthora capsiciin vitro. The bioassay results showed that the target compounds possessed moderate to good fungicidal activities against P. capsici, among which oxime ether compound I shows the highest fungicidal activity in vitro (EC50 = 0.0104μg/mL) which is higher than dimethomorph (EC50 = 0.1148μg/mL) and diacetylenyl amide (EC50 = 0.040μg/mL). Compared with oxime ether compounds (the two nitrogen atoms are on the opposite sides), the activities of oxime ester compounds were significantly reduced. It is different from the com. fungicide fluoxapiprolin, and the activities of the compounds with the two nitrogen atoms on the same side were significantly reduced compared to the compounds with the two nitrogen atoms on the opposite sides. Moreover, some compounds showed moderate to good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. SEM of compound I on the hyphae morphol. showed that compound I might cause mycelial abnormalities of P. capsici. In the experimental materials used by the author, we found Piperidine-4-carboxamide(cas: 39546-32-2Application of 39546-32-2)

Piperidine-4-carboxamide(cas: 39546-32-2) belongs to anime. Milder oxidation, using reagents such as NaOCl, can remove four hydrogen atoms from primary amines of the type RCH2NH2 to form nitriles (R―C≡N), and oxidation with reagents such as MnO2 can remove two hydrogen atoms from secondary amines (R2CH―NHR′) to form imines (R2C=NR′). Tertiary amines can be oxidized to enamines (R2C=CHNR2) by a variety of reagents.Application of 39546-32-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Name: tert-Butyl 4-aminopiperidine-1-carboxylateIn 2019 ,《Synthesis, docking and antibacterial studies of more potent amine and hydrazone rifamycin congeners than rifampicin》 was published in European Journal of Medicinal Chemistry. The article was written by Pyta, Krystian; Janas, Anna; Szukowska, Monika; Pecyna, Paulina; Jaworska, Marcelina; Gajecka, Marzena; Bartl, Franz; Przybylski, Piotr. The article contains the following contents:

New rifamycin congeners with incorporated amine and hydrazone substituents leading to lipophilic and/or basic nature and altered rigidity of modified C(3) arm were synthesized and structurally characterized in detail. NMR spectroscopic studies at different temperatures indicate two types of structures of rifamycin congeners that are realized in solution: zwitterionic and non-ionic forms in dependence of the basicity of modified C(3) arm. The presence of rifamycin congeners in these two possible forms has a significant impact on the physico-chem. parameters such as lipophilicity (clogP) and water solubility and different binding mode of the C(3) arm of antibiotic at RNAP binding pocket (mol. target) leading to different antibacterial potency. The highest antibacterial potency against S. aureus (including MRSA and MLSB strains) and S. epidermidis strains, even higher than reference rifampicin and rifaximin antibiotics, was found for rifamycin congeners bearing at the C(3) arm relatively rigid and basic substituents (bipiperidine and guanidine groups). These modifications provide favorable docking mode and excellent water solubility resulting in high potency (MICs 0.0078 μg/mL what gives ∼ 8.5 nM), irresp. whether rifamycin congener is a tertiary amine or hydrazone. In turn, for a higher antibacterial potency of rifamycin congeners against E. faecalis strain (MICs 0.5 μg/mL that is 0.6 μM) as compared to Rif and Rifx, the most crucial factors are: bulkiness and the lipophilic character of the end of the C(3) rebuilt arm. The experimental part of the paper was very detailed, including the reaction process 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. 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.Name: tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Recommanded Product: 109384-19-2In 2020 ,《Discovery of Bispecific Antagonists of Retinol Binding Protein 4 That Stabilize Transthyretin Tetramers: Scaffolding Hopping, Optimization, and Preclinical Pharmacological Evaluation as a Potential Therapy for Two Common Age-Related Comorbidities》 appeared in Journal of Medicinal Chemistry. The author of the article were Cioffi, Christopher L.; Muthuraman, Parthasarathy; Raja, Arun; Varadi, Andras; Racz, Boglarka; Petrukhin, Konstantin. The article conveys some information:

Accumulation of cytotoxic lipofuscin bisretinoids may contribute to atrophic age-related macular degeneration (AMD) pathogenesis. Retinal bisretinoid synthesis depends on the influx of serum all-trans-retinol delivered via a tertiary retinol binding protein 4 (RBP4)-transthyretin (TTR)-retinol complex. We previously identified selective RBP4 antagonists that dissociate circulating RBP4-TTR-retinol complexes, reduce serum RBP4 levels, and inhibit bisretinoid synthesis in models of enhanced retinal lipofuscinogenesis. However, the release of TTR by selective RBP4 antagonists may be associated with TTR tetramer destabilization and, potentially, TTR amyloid formation. We describe herein the identification of bispecific RBP4 antagonist-TTR tetramer kinetic stabilizers. Standout analog I possesses suitable potency for both targets, significantly lowers mouse plasma RBP4 levels, and prevents TTR aggregation in a gel-based assay. This new class of bispecific compounds may be especially important as a therapy for dry AMD patients who have another common age-related comorbidity, senile systemic amyloidosis, a nongenetic disease associated with wild-type TTR misfolding.tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Recommanded Product: 109384-19-2) was used in this study.

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.Recommanded Product: 109384-19-2

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2022,Goldberg, Frederick W.; Ting, Attilla K. T.; Beattie, David; Lamont, Gillian M.; Fallan, Charlene; Finlay, M. Raymond V.; Williamson, Beth; Schimpl, Marianne; Harmer, Alexander R.; Adeyemi, Oladipupo B.; Nordell, Par; Cronin, Anna S.; Vazquez-Chantada, Mercedes; Barratt, Derek; Ramos-Montoya, Antonio; Cadogan, Elaine B.; Davies, Barry R. published an article in ACS Medicinal Chemistry Letters. The title of the article was 《Optimization of hERG and Pharmacokinetic Properties for Basic Dihydro-8H-purin-8-one Inhibitors of DNA-PK》.Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate The author mentioned the following in the article:

Series of neutral DNA-PKcs inhibitors were modified to incorporate a basic group, with the rationale that increasing the volume of distribution while maintaining good metabolic stability should increase the half-life. However, adding a basic group introduced hERG activity and basic compounds with modest hERG activity (IC50 = 10-15μM) prolonged QTc (time from the start of the Q wave to the end of the T wave, corrected by heart rate) in an anesthetized guinea pig cardiovascular model. Further optimization were necessary, including modulation of pKa, to identify I, which combines low hERG activity (IC50 = 75μM) with excellent kinome selectivity and favorable pharmacokinetic properties. In the experiment, the researchers used tert-Butyl 4-aminopiperidine-1-carboxylate(cas: 87120-72-7Quality Control of 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.Quality Control of tert-Butyl 4-aminopiperidine-1-carboxylate

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Wang, Liujiao; You, Rixin; Ling, Yuxuan; Xie, Yu; Mei, Cenyu; Li, Ziming; Wang, Fanghui published an article in 2021. The article was titled 《Covalent cross-linked anion exchange membrane based on poly(biphenyl piperidine) and poly(styrene-b-(ethylene-co-butylene)-b-styrene): preparation and properties》, and you may find the article in Polymer-Plastics Technology and Materials.Computed Properties of C6H11NO The information in the text is summarized as follows:

Poly(biphenyl piperidine) and polystyrene-b-poly(ethylene-co-butylene)-b-polystyrene were cross-linked to form a polymer backbone, piperidine as the ionic conducting group to improve the chem. stability of the anion exchange membrane. Results indicate that the cross-linked membranes could still retain more than 95% of ion conductivity after being soaked in 1-M KOH solution at 80°C for 800 h, indicating that this cross-linked membrane exhibits good alk. stability. The optimized microphase separation morphol. could promote the ion transport (81.68 mS/cm, 80°C). The cross-linked structure helped to restrain the swelling behavior. The membrane became flexible after crosslinking, which is beneficial to the fuel-cell assembly. In the part of experimental materials, we found many familiar compounds, such as 1-Methyl-4-piperidone(cas: 1445-73-4Computed Properties of C6H11NO)

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.Computed Properties of C6H11NO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Renk, Dana R.; Skraban, Marcel; Bier, Dirk; Schulze, Annette; Wabbals, Erika; Wedekind, Franziska; Neumaier, Felix; Neumaier, Bernd; Holschbach, Marcus published an article in 2021. The article was titled 《Design, synthesis and biological evaluation of Tozadenant analogues as adenosine A2A receptor ligands》, and you may find the article in European Journal of Medicinal Chemistry.Synthetic Route of C10H19NO3 The information in the text is summarized as follows:

With the aim to obtain potent adenosine A2A receptor (A2AR) ligands, a series of eighteen derivatives of 4-hydroxy-N-(4-methoxy-7-morpholin-4-yl-1,3-benzo[d]thiazol-2-yl)-4-methylpiperidine-1-carboxamide were designed and synthesized. The target compounds were obtained by a chem. building block principle that involved reaction of the appropriate aminobenzothiazole Ph carbamates with either com. available or readily synthesized functionalized piperidines. Ki values for human A2AR ranged from 2.4 to 38 nM, with more than 120-fold selectivity over A1 receptors for all evaluated compounds except 4-Fluoro-4-(hydroxymethyl)-N-(4-methoxy-7-morpholinobenzo[d]thiazol-2-yl)piperidine-1-carboxamide which had a Ki of 361 nM and 18-fold selectivity. The most potent fluorine-containing derivatives exhibited Ki values of 4.9 nM, 3.6 nM and 2.8 nM for the human A2AR. Interestingly, the corresponding values for rat A2AR were found to be four to five times higher. Their binding to A2AR was further confirmed by radiolabeling with 18F and in vitro autoradiog. in rat brain slices, which showed almost exclusive striatal binding and complete displacement by the A2AR antagonist ZM 241385. Authors conclude that these compounds represent potential candidates for the visualization of the A2A receptor and open pathways to novel therapeutic treatments of neurodegenerative disorders or cancer. In the experimental materials used by the author, we found tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Synthetic Route of 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.Synthetic Route of C10H19NO3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Zhang, Minkui; Tang, Li; Jiang, Liu; Wei, Jun; Hu, Yongzhou; Sheng, Rong published their research in European Journal of Medicinal Chemistry in 2021. The article was titled 《Identification of N-phenyl-3-methoxy-4-pyridinones as orally bioavailable H3 receptor antagonists and β-amyloid aggregation inhibitors for the treatment of Alzheimer’s disease》.Name: tert-Butyl 4-hydroxypiperidine-1-carboxylate The article contains the following contents:

Based on our previous work, a series of N-phenyl-3-methoxy-4-pyridinone derivatives were designed as orally bioavailable dual functional agents for therapy of Alzheimer’s disease, through introducing alkyloxy moiety into 4-pyridinone ring to avoid the possible phase II metabolism of 3-hydroxy-4-pyridinone in lead compound 3-hydroxy-2-methyl-1-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl)-pyridin-4(1H)-one (4). In vitro studies indicated that most of these compounds exhibit excellent H3 receptor antagonistic activities and potent self-induced Aβ1-40/Aβ1-42 aggregation inhibitory activities. In particular, 3-methoxy-1-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl)-pyridin-4(1H)-one (7i) demonstrated IC50 value of 0.52 nM in H3R antagonism and good selectivity over other histamine receptor subtypes. The transmission electron microscopy (TEM) images showed that compound 7i can inhibit self-mediated Aβ1-40/Aβ1-42 aggregation efficiently. As expected, it exhibited desirable pharmacokinetic properties in plasma and good BBB permeability. Furthermore, compound 7i can efficiently block (R)-α-methylhistamine- induced dipsogenia and reverse scopolamine-induced learning deficits of rats. All above results indicated that compound 7i was a promising orally bioavailable dual functional agents with potential use in the treatment of Alzheimer’s disease. In addition to this study using tert-Butyl 4-hydroxypiperidine-1-carboxylate, there are many other studies that have used tert-Butyl 4-hydroxypiperidine-1-carboxylate(cas: 109384-19-2Name: tert-Butyl 4-hydroxypiperidine-1-carboxylate) was used in this study.

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