Category: piperidines

Muste, Cathy published the artcileBTK-inhibitor drug covalent binding to lysine in human serum albumin using LC-MS/MS, Safety of (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, the publication is Drug Metabolism and Pharmacokinetics (2022), 100433, database is CAplus and MEDLINE.

Irreversible Bruton’s tyrosine kinase (BTK) inhibitor drugs are designed to bind covalently to a free-thiol cysteine in the BTK protein active site. However, these reactive drugs bind to off-target proteins as well. In this study, seven BTK-inhibitor drugs containing acrylamide warheads were incubated with human serum albumin (HSA) and analyzed using an LC-MS/MS peptide mapping approach to determine the amino acid sites of drug covalent binding. Significant adduction at the free-thiol cysteine of HSA was only observed for two of the drugs. However, significant adduction was observed for at least four lysine residues. This is just a small percentage of the 59 total lysine residues in HSA. These four lysine residues are likely partially buried, accessible to the drugs, and exist at least partially in a neutral state. The levels of adduction observed in the in-vitro exptl. conditions are only indicative of a relative propensity for adduction with the individual lysine residues of HSA, and are not in-vivo predictions. Widespread off-target lysine binding could impact clearance and bioavailability for irreversible inhibitor drugs. However, the extent of the impact on clearance may be limited in comparison to conjugation with glutathione.

Drug Metabolism and Pharmacokinetics published new progress about 1971920-73-6. 1971920-73-6 belongs to piperidines, auxiliary class Other Aliphatic Heterocyclic,Piperidine,Alkenyl,Amine,Benzene,Ether,Inhibitor,Inhibitor, name is (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one, and the molecular formula is C26H25N5O3, Safety of (R)-1-(1-Acryloylpiperidin-3-yl)-4-amino-3-(4-phenoxyphenyl)-1H-imidazo[4,5-c]pyridin-2(3H)-one.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Wu, Yong-Jin published the artcileDevelopment of New Benzenesulfonamides As Potent and Selective Na_v1.7 Inhibitors for the Treatment of Pain, Computed Properties of 14613-37-7, the publication is Journal of Medicinal Chemistry (2017), 60(6), 2513-2525, database is CAplus and MEDLINE.

By taking advantage of certain features in piperidine (I), the authors developed a novel series of cyclohexylamine- and piperidine-based benzenesulfonamides as potent and selective Na_v1.7 inhibitors. However, 4-((((1S,4S)-4-aminocydohexyl)methyl)amino)-5-chloro-2-fluoro-N-(thiazol-2-yl)benzenesulfonamide (24), one of the early analogs, failed to reduce phase 2 flinching in the mouse formalin test even at a dose of 100 mpk PO due to insufficient DRG exposure attributed to poor membrane permeability. Two analogs with improved membrane permeability showed much increased DRG concentrations at doses of 30 mpk PO but, confoundingly, only one of these was effective in the formalin test. More data are needed to understand the disconnect between efficacy and exposure relationships.

Journal of Medicinal Chemistry published new progress about 14613-37-7. 14613-37-7 belongs to piperidines, auxiliary class Piperidine,Amine, name is (1-Methylpiperidin-3-yl)methanamine, and the molecular formula is C12H10FeO4, Computed Properties of 14613-37-7.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Kozikowski, Alan P. published the artcileIdentification of a Glycogen Synthase Kinase-3β Inhibitor that Attenuates Hyperactivity in CLOCK Mutant Mice, HPLC of Formula: 170364-89-3, the publication is ChemMedChem (2011), 6(9), 1593-1602, database is CAplus and MEDLINE.

Bipolar disorder is characterized by a cycle of mania and depression, which affects approx. 5 million people in the United States. Current treatment regimes include the so-called “mood-stabilizing drugs”, such as lithium and valproate that are relatively dated drugs with various known side effects. Glycogen synthase kinase-3β (GSK-3β) plays a central role in regulating circadian rhythms, and lithium is known to be a direct inhibitor of GSK-3β. We designed a series of second generation benzofuran-3-yl-(indol-3-yl)maleimides containing a piperidine ring that possess IC₅₀ values in the range of 4 to 680 nM against human GSK-3β. Compound 3a (I) exhibits reasonable kinase selectivity and promising preliminary absorption, distribution, metabolism, and excretion (ADME) data. The administration of this compound at doses of 10 to 25 mg kg^-1 resulted in the attenuation of hyperactivity in amphetamine/chlordiazepoxide-induced manic-like mice together with enhancement of prepulse inhibition, similar to the effects found for valproate (400 mg kg^-1) and the antipsychotic haloperidol (1 mg kg^-1). We also tested this compound in mice carrying a mutation in the central transcriptional activator of mol. rhythms, the CLOCK gene, and found that the same compound attenuates locomotor hyperactivity in response to novelty. This study further demonstrates the use of inhibitors of GSK-3β in the treatment of manic episodes of bipolar/mood disorders, thus further validating GSK-3β as a relevant therapeutic target in the identification of new therapies for bipolar patients.

ChemMedChem published new progress about 170364-89-3. 170364-89-3 belongs to piperidines, auxiliary class Indole,Piperidine,Amide, name is tert-Butyl 4-(1H-indol-1-yl)piperidine-1-carboxylate, and the molecular formula is C18H24N2O2, HPLC of Formula: 170364-89-3.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Han, Si-yin published the artcileMaillard reaction of sisal hemp juice hydrolysate and its volatile composition, Recommanded Product: 1-Ethylpiperidin-3-ol, the publication is Shipin Gongye (Shanghai, China) (2014), 35(3), 14-17, database is CAplus.

Sisal hemp juice was hydrolyzed by muriatic acid, hydrolyzate obtained from that would have Maillard reaction, and volatile components of the Maillard reaction products were detected. A hydrolysis of sisal hemp juice by muriatic acid 6 mol/L, volume ratio of muriatic acid and sisal juice 4:1 and hydrolysis in 100 °C for 14 h leaded to a degree hydrolysis of 16.8%. The highest browning degree was measured in the hydrolyzate at pH 7 after incubation in 100 °C for 30 min. Under this condition the volatile components of these Maillard reaction products mainly included 8 categories via the detection of GC-MS, which were alc., aldehyde, ketone, acid, ester, phenol, alkene and furan, and it can be developed as a natural fumette for tobacco.

Shipin Gongye (Shanghai, China) published new progress about 13444-24-1. 13444-24-1 belongs to piperidines, auxiliary class Piperidine,Alcohol, name is 1-Ethylpiperidin-3-ol, and the molecular formula is C7H15NO, Recommanded Product: 1-Ethylpiperidin-3-ol.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Wu, Ting-Ting published the artcileDesign, synthesis and bioevaluation of novel substituted triazines as potential dual PI3K/mTOR inhibitors, Application In Synthesis of 39546-32-2, the publication is European Journal of Medicinal Chemistry (2020), 112637, database is CAplus and MEDLINE.

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.

European Journal of Medicinal Chemistry published new progress about 39546-32-2. 39546-32-2 belongs to piperidines, auxiliary class Piperidine,Amine,Amide, name is Piperidine-4-carboxamide, and the molecular formula is C9H8BrNO4, Application In Synthesis of 39546-32-2.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Meng, Genyi published the artcileModular click chemistry libraries for functional screens using a diazotizing reagent, Safety of (1-Methylpiperidin-3-yl)methanamine, the publication is Nature (London, United Kingdom) (2019), 574(7776), 86-89, database is CAplus and MEDLINE.

Alkyl and aryl azides were prepared from the corresponding primary alkyl and aryl amines by reaction with fluorosulfonyl azide generated in situ from a fluorosulfonylimidazolium triflate and sodium azide, expanding access to azides and both to the 1,2,3-triazoles derived from them and to functional screens employing them. The method allowed the preparation of a library of >1000 azides from the corresponding amines; the azide library underwent copper-catalyzed azide-alkyne cycloaddition reactions to yield a library of >1000 1,2,3-triazoles.

Nature (London, United Kingdom) published new progress about 14613-37-7. 14613-37-7 belongs to piperidines, auxiliary class Piperidine,Amine, name is (1-Methylpiperidin-3-yl)methanamine, and the molecular formula is C7H16N2, Safety of (1-Methylpiperidin-3-yl)methanamine.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Chayajarus, Kampanart published the artcileEfficient synthesis of carbohydrate thionolactones, SDS of cas: 4972-31-0, the publication is Tetrahedron Letters (2006), 47(21), 3517-3520, database is CAplus.

Carbohydrate thionolactones, e.g. I, may be efficiently synthesized from the corresponding 1-thio sugars via a two-step procedure involving formation of a glycosyl phenylthiosulfinate by treatment with either phenylsulfinyl chloride or 1-(phenylsulfinyl)piperidine (BSP), and subsequent thermal elimination in toluene.

Tetrahedron Letters published new progress about 4972-31-0. 4972-31-0 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-(Phenylsulfinyl)piperidine, and the molecular formula is C11H15NOS, SDS of cas: 4972-31-0.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Hu, Bo published the artcileFive-Membered Ring Nitroxide Radical: A New Class of High-Potential, Stable Catholyte for Neutral Aqueous Organic Redox Flow Batteries, COA of Formula: C9H17NO, the publication is Advanced Functional Materials (2021), 31(35), 2102734, database is CAplus.

The utilization of redox-active and stable cyclic nitroxide radicals (CNRs) holds a great promise in neutral aqueous organic redox flow batteries (AORFBs) for large-scale energy storage. Herein, a new class of CNRs with five-membered ring pyrrolidine and pyrroline motifs for AORFBs is reported. By rational mol. engineering of introducing CC double bond into the pyrrolidine-based mol., 3-carbamoyl-2,2,5,5-tetramethylpyrroline-1-oxyl (CPL) with a high redox potential of 0.76 V (vs Ag/AgCl) is demonstrated, which is 160 mV higher than the common 2,2,6,6-tetramethylpiperidine 1-oxyl derivatives with a six-membered ring as the core structure. D. functional theory calculations reveal that the much enhanced redox potential for CPL is largely contributed by lowered standard free energy in reduction reaction and charge population sum of NO radical head. When paired with the BTMAP-viologen anolyte, the CPL-based AORFB delivers constant capacity retention of up to 99.96%/cycle over 500 cycles.

Advanced Functional Materials published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C9H17NO, COA of Formula: C9H17NO.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Shen, Zhuo published the artcileFe-based carbonitride as Fenton-like catalyst for the elimination of organic contaminants, Formula: C9H17NO, the publication is Environmental Research (2021), 110486, database is CAplus and MEDLINE.

The Fenton-like process has been regarded as a clean and efficient approach to generate reactive oxygen species (ROS) to deal with the ever-growing environmental pollution. However, developing improved catalysts with adequate activity and stability remains a long-term goal for practical application. Herein, crystalline carbon nanotubes (CNTs) interconnected Fe/Fe₃C-doped nanoporous carbonitride (Fe-NC) was easily prepared by the pyrolysis of ZIF-8 confined with Fe³⁺. The obtained Fe-NCs possessed high degrees of graphitic carbon and nitrogen. Such Fe-NCs can enhance the activation of peroxymonosulfate (PMS) for the removal of multiple organic contaminants. The optimized Fe-NC/PMS system exhibited impressive catalytic performance, with a TOF as high as 4.43 min^-1 for 3BF degradation, and the removal efficiency of other dyes, phenols and antibiotics was up to 96.2% within 10 min. The removal efficiency of 3BF was 93.4% within 10 min with extremely low Fe ions leaching (<0.052 mg/L) even after 5 cycles. In addition, the effects of pH on the catalytic performance demonstrated that the decomposition of 3BF exceeded 95.6% even when the initial pH varied from 5 to 10. We confirmed that SO₄·^–, ·OH, O₂·^–,and ¹O₂ ere generated in the catalytic system of Fe-NC/PMS, which played a critical role in degrading the organics These findings provide new insights into the design of environmentally friendly Fenton-like catalysts with high efficiency and favorable stability in environmental remediation.

Environmental Research published new progress about 826-36-8. 826-36-8 belongs to piperidines, auxiliary class Natural product, name is 2,2,6,6-Tetramethylpiperidin-4-one, and the molecular formula is C44H28ClFeN4, Formula: C9H17NO.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem

Padungros, Panuwat published the artcileSynthesis and Reactivity of 4′-Deoxypentenosyl Disaccharides, Formula: C11H15NOS, the publication is Journal of Organic Chemistry (2014), 79(11), 4878-4891, database is CAplus and MEDLINE.

4-Deoxypentenosides (4-DPs) are versatile synthons for rare or higher-order pyranosides, and they provide an entry for structural diversification at the C5 position. Previous studies have shown that 4-DPs undergo stereocontrolled DMDO oxidation; subsequent epoxide ring-openings with various nucleophiles can proceed with both anti or syn selectivity. Here, we report the synthesis of α- and β-linked 4′-deoxypentenosyl (4′-DP) disaccharides, and we investigate their post-glycosylation C₅‘ additions using the DMDO oxidation/ring-opening sequence. The α-linked 4’-DP disaccharides were synthesized by coupling thiophenyl 4-DP donors with glycosyl acceptors using BSP/Tf₂O activation, whereas β-linked 4′-DP disaccharides were generated by the decarboxylative elimination of glucuronyl disaccharides under microwave conditions. Both α- and β-linked 4′-DP disaccharides could be epoxidized with high stereoselectivity using DMDO. In some cases, the α-epoxypentenosides could be successfully converted into terminal L-iduronic acids via the syn addition of 2-furyl-zinc bromide. These studies support a novel approach to oligosaccharide synthesis, in which the stereochem. configuration of the terminal 4′-DP unit is established at a post-glycosylation stage.

Journal of Organic Chemistry published new progress about 4972-31-0. 4972-31-0 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-(Phenylsulfinyl)piperidine, and the molecular formula is C11H15NOS, Formula: C11H15NOS.

Referemce:
https://en.wikipedia.org/wiki/Piperidine,
Piperidine | C5H11N – PubChem