Day: October 14, 2022

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

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

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

《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

《Preparation and evaluation of soluble epoxide hydrolase inhibitors with improved physical properties and potencies for treating diabetic neuropathic pain》 was written by Lee, Kin Sing Stephen; Ng, Jen C.; Yang, Jun; Hwang, Sung-Hee; Morisseau, Christophe; Wagner, Karen; Hammock, Bruce D.. Application of 87120-72-7This research focused onurea drug design preparation sEH inhibitor diabetic neuropathic pain; Drug design; Drug target residence time; Inhibitor; Neuropathic pain; Physical properties; Soluble epoxide hydrolase. The article conveys some information:

Soluble epoxide hydrolase (sEH), a novel therapeutic target for neuropathic pain, is a largely cytosolic enzyme that degrades epoxy-fatty acids (EpFAs), an important class of lipid signaling mols. Many inhibitors of sEH have been reported, and to date, the 1,3-disubstituted urea has the highest affinity reported for the sEH among the central pharmacophores evaluated. An earlier somewhat water soluble sEH inhibitor taken to the clinic for blood pressure control had mediocre potency (both affinity and kinetics) and a short in vivo half-life. We undertook a study to overcome these difficulties, but the sEH inhibitors carrying a 1,3-disubstituted urea often suffer poor phys. properties that hinder their formulation. In this report, we described new strategies to improve the phys. properties of sEH inhibitors with a 1,3-disubstituted urea while maintaining their potency and drug-target residence time (a complementary in vitro parameter) against sEH. To our surprise, we identified two structural modifications that substantially improve the potency and phys. properties of sEH inhibitors carrying a 1,3-disubstituted urea pharmacophore. Such improvements will greatly facilitate the movement of sEH inhibitors to the clinic. 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

《Site-selective α-C-H Functionalization of Trialkylamines via Reversible HAT-Catalysis》 was written by Shen, Yangyang; Funez-Ardoiz, Ignacio; Schoenebeck, Franziska; Rovis, Tomislav. Formula: C6H11NOThis research focused ontrialkylamine regioselective functionalization reversible HAT catalysis. The article conveys some information:

Despite the recent breakthrough of catalytic alkylation of dialkylamines, the selective α-C(sp3)-H bond functionalization of widely available trialkylamine scaffolds holds promise to streamline complex trialkylamine synthesis, accelerate drug discovery and execute late-stage pharmaceutical modification with complementary reactivity. However, the canonical methods always result in functionalization at the less-crowded site. Herein, authors describe a solution to switch the reaction site through fundamentally overcoming the steric control that dominates such processes. By rapidly establishing an equilibrium between α-amino C(sp3)-H bonds and a highly electrophilic thiol radical via reversible hydrogen atom transfer, authors leverage a slower radical-trapping step with electron-deficient olefins to selectively forge a C(sp3)-C(sp3) bond with the more-crowded α-amino radical, with the overall selectivity guided by Curtin-Hammett principle. This subtle reaction profile has unlocked a new strategic concept in direct C-H functionalization arena for forging C-C bonds from a diverse set of trialkylamines with high levels of site-selectivity and preparative utility. The broad consequences of this dynamic system, together with the ability to forge N-substituted quaternary carbon centers and implement late-stage functionalization techniques, holds potential to streamline complex trialkylamine synthesis and accelerate small-mol. drug discovery. In the experiment, the researchers used 1-Methyl-4-piperidone(cas: 1445-73-4Formula: C6H11NO)

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.Formula: C6H11NO

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Related Products of 126832-81-3On October 20, 2017 ,《Discovery of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: Design, synthesis, and biological evaluation》 was published in European Journal of Medicinal Chemistry. The article was written by Wang, Zhengyu; Shi, Xiaofan; Zhang, Huan; Yu, Liang; Cheng, Yanhua; Zhang, Hefeng; Zhang, Huibin; Zhou, Jinpei; Chen, Jing; Shen, Xu; Duan, Wenhu. The article contains the following contents:

Glucokinase (GK) activators are being developed for the treatment of type 2 diabetes mellitus (T2DM). However, existing GK activators have risks of hypoglycemia caused by over-activation of GK in islet cells and dyslipidemia caused by over-activation of intrahepatic GK. In the effort to mitigate risks of hypoglycemia and dyslipidemia while maintaining the promising efficacy of GK activator, the authors investigated a series of cycloalkyl-fused N-thiazol-2-yl-benzamides as tissue non-specific partial GK activators. This led to the identification of compound 72 (tert-Bu(S)-2-(3-(4-(azetidine-1-carbonyl)phenoxy)-5-((1-methoxypropan-2-yl)oxy)benzamido)-6,7-dihydrothiazolo[5,4-c]pyridine-5(4H)-carboxylate) that showed a good balance between in vitro potency and enzyme kinetic parameters. Compound 72 also protected β-cells from streptozotocin-induced apoptosis. Chronic treatment of compound 72 demonstrated its potent activity in regulation of glucose homeostasis and low risk of dyslipidemia with diabetic db/db mice in oral glucose tolerance test (OGTT). Moreover, acute treatment of compound 72 did not induce hypoglycemia in C57BL/6J mice even at 200 mg/kg via oral administration. The results came from multiple reactions, including the reaction of 1-Pyridin-4-ylpiperidin-4-one(cas: 126832-81-3Related Products of 126832-81-3)

1-Pyridin-4-ylpiperidin-4-one(cas: 126832-81-3) belongs to piperidines. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions. Related Products of 126832-81-3

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Guo, Shuai; Liu, Lidong; Guo, Xin; Liu, Tiecheng; Li, Xingcan; Li, Guangyu published an article in Journal of Environmental Chemical Engineering. The title of the article was 《Unveiling the mechanism of NOx precursor formation during sewage sludge pyrolysis: Effects of carbohydrate-protein interactions》.Recommanded Product: Triacetonamine The author mentioned the following in the article:

Municipal sewage sludge poses environmental and health risks, and thus, requires proper disposal using pyrolytic techniques. However, these techniques are hindered by the production of NH3 and HCN (NOx precursors) by the sludge. Hence, a comprehensive understanding of NH3 and HCN formation during sludge pyrolysis is required to minimize its NOx footprint. As sludge N mainly occurs in proteins forms, its transformations can be modeled using amino acids. Here, we aimed to the study the mechanism by which carbohydrates influence the formation of NOx precursors during sludge protein pyrolysis at different temperatures using glutamic acid, tyrosine, and histidine as protein models and cellulose and lignin as carbohydrate models. During pyrolysis, the release of NH3 and HCN was promoted by high temperatures and inhibited by carbohydrates. Despite this inhibitory effect, the results suggested that the release of NH3 should be considered for samples rich in aliphatic amino acids. For glutamic acid and tyrosine, NOx precursor formation was inhibited by N fixation in coke under the action of volatiles produced during carbohydrate pyrolysis. For glutamic acid, adding cellulose and lignin increased the coke-N content by 25.32% and 44.73% at 700°C. For histidine, this effect was ascribed to the ring-opening reactions induced by the free radical products of carbohydrate decomposition and the enhanced transfer of N-containing compounds to tar after ring-opening recombination. Further, heterocyclic-N within tar increased to 69.12% due to lignin-histidine interactions at 700°C. The results of this study can assist in regulating sludge protein pyrolysis intended for minimizing the production of NOx precursors. In the experiment, the researchers used many compounds, for example, Triacetonamine(cas: 826-36-8Recommanded Product: Triacetonamine)

Triacetonamine(cas: 826-36-8) 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.Recommanded Product: Triacetonamine

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

In 2019,Energies (Basel, Switzerland) included an article by Devia-Orjuela, John Steven; Alvarez-Pugliese, Christian E.; Donneys-Victoria, Dayana; Cabrales, Nilson Marriaga; Ho, Luz Edith Barba; Brem, Balazs; Sauciuc, Anca; Gal, Emese; Espin, Douglas; Schichtel, Martin; Lang, Dimitrina; Giardinelli, Sebastiano; Briceno, Maria. Recommanded Product: Triacetonamine. The article was titled 《Evaluation of press mud, vinasse powder and extraction sludge with ethanol in a pyrolysis process》. The information in the text is summarized as follows:

The effluents of the sugar and bio-ethanol industry, mainly vinasse as well as lignocellulosic waste, are produced in high volumes Therefore, their treatment and valorization would reduce the environmental impact and make this industry more productive and competitive. The purpose of this study was to determine the potential use of press mud (lignocellulosic waste), vinasse powder, and vinasse sludge from an extraction process with ethanol, as raw materials for conventional pyrolysis evaluating the physicochem. characteristics that affect this thermochem. process, such as calorific power, d., ash content, volatile material, moisture and nitrogen, sulfur, carbon and hydrogen content, thermogravimetric profile, and quantification of lignin cellulose and hemicellulose. The batch pyrolysis experiments showed that all three wastes could be converted successfully into more valuable products. The powder vinasse led to the formation of the lowest content of bio-char (42.7%), the highest production of volatiles (61.6 weight%), and the lowest ash content (20.5 weight%). Besides, it showed the high heating value of 15.63 MJ/kg. Meanwhile, the extraction sludge presented the highest liquid yield (32%) with the lowest gas formation (18.2 weight%) and the lowest heating value of 8.57 MJ/kg. Thus, the sludge could be a good feedstock for production of bio-oil and bio-char. In the experiment, the researchers used many compounds, for example, Triacetonamine(cas: 826-36-8Recommanded Product: Triacetonamine)

Triacetonamine(cas: 826-36-8) 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.Recommanded Product: Triacetonamine

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem

Pierson, Pascale David; Fettes, Alec; Freichel, Christian; Gatti-McArthur, Silvia; Hertel, Cornelia; Huwyler, Jorg; Mohr, Peter; Nakagawa, Toshito; Nettekoven, Matthias; Plancher, Jean-Marc; Raab, Susanne; Richter, Hans; Roche, Olivier; Rodriguez Sarmiento, Rosa Maria; Schmitt, Monique; Schuler, Franz; Takahashi, Tadakatsu; Taylor, Sven; Ullmer, Christoph; Wiegand, Ruby published an article in Journal of Medicinal Chemistry. The title of the article was 《5-Hydroxyindole-2-carboxylic Acid Amides: Novel Histamine-3 Receptor Inverse Agonists for the Treatment of Obesity》.HPLC of Formula: 851847-62-6 The author mentioned the following in the article:

Obesity is a major risk factor in the development of conditions such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and cancer. Several pieces of evidence across different species, including primates, underscore the implication of the histamine 3 receptor (H3R) in the regulation of food intake and body weight and the potential therapeutic effect of H3R inverse agonists. A pharmacophore model, based on public information and validated by previous investigations, was used to design several potential scaffolds. Out of these scaffolds, the 5-hydroxyindole-2-carboxylic acid amide appeared to be of great potential as a novel series of H3R inverse agonist. Extensive structure-activity relationships revealed the interconnectivity of microsomal clearance and hERG (human ether-a-go-go-related gene) affinity with lipophilicity, artificial membrane permeation, and basicity. This effort led to the identification of compounds reversing the (R)-α-methylhistamine-induced water intake increase in Wistar rats and, further, reducing food intake in diet-induced obese Sprague-Dawley rats. Of these, the biochem., pharmacokinetic, and pharmacodynamic characteristics of (4,4-difluoropiperidin-1-yl)[1-isopropyl-5-(1-isopropylpiperidin-4-yloxy)-1H-indol-2-yl]methanone 36 are detailed. In addition to this study using 1-Cyclopropylpiperidin-4-ol, there are many other studies that have used 1-Cyclopropylpiperidin-4-ol(cas: 851847-62-6HPLC of Formula: 851847-62-6) was used in this study.

1-Cyclopropylpiperidin-4-ol(cas: 851847-62-6) belongs to piperidines. Piperidine derivatives are also used in solid-phase peptide synthesis (SPPS) and many degradation reactions. HPLC of Formula: 851847-62-6

Referemce:
Piperidine – Wikipedia,
Piperidine | C5H11N – PubChem