Day: November 21, 2022

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

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

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

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

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

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

Faul, Margaret M. published the artcileStrategies for the synthesis of N-(azacycloalkyl)bisindolylmaleimides: selective inhibitors of PKCβ, HPLC of Formula: 170364-89-3, the publication is Tetrahedron (2003), 59(36), 7215-7229, database is CAplus.

N-(Azacycloalkyl)bisindolylmaleimides such as I have been identified to be selective inhibitors of PKCβ. This manuscript will describe the synthetic approaches employed to prepare this class of compounds that resulted in development of efficient methods for preparation of N-(azacycloalkyl)indoles, indole-3-acetamides, and indole-3-glyoxylate esters.

Tetrahedron 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

Stetkova, Monika published the artcileCDK9 activity is critical for maintaining MDM4 overexpression in tumor cells, HPLC of Formula: 1702809-17-3, the publication is Cell Death & Disease (2020), 11(9), 754, database is CAplus and MEDLINE.

The identification of the essential role of cyclin-dependent kinases (CDKs) in the control of cell division has prompted the development of small-mol. CDK inhibitors as anticancer drugs. For many of these compounds, the precise mechanism of action in individual tumor types remains unclear as they simultaneously target different classes of CDKs – enzymes controlling the cell cycle progression as well as CDKs involved in the regulation of transcription. CDK inhibitors are also capable of activating p53 tumor suppressor in tumor cells retaining wild-type p53 gene by modulating MDM2 levels and activity. In the current study, we link, for the first time, CDK activity to the overexpression of the MDM4 (MDMX) oncogene in cancer cells. Small-mol. drugs targeting the CDK9 kinase, dinaciclib, flavopiridol, roscovitine, AT-7519, SNS-032, and DRB, diminished MDM4 levels and activated p53 in A375 melanoma and MCF7 breast carcinoma cells with only a limited effect on MDM2. These results suggest that MDM4, rather than MDM2, could be the primary transcriptional target of pharmacol. CDK inhibitors in the p53 pathway. CDK9 inhibitor atuveciclib downregulated MDM4 and enhanced p53 activity induced by nutlin-3a, an inhibitor of p53-MDM2 interaction, and synergized with nutlin-3a in killing A375 melanoma cells. Furthermore, we found that human pluripotent stem cell lines express significant levels of MDM4, which are also maintained by CDK9 activity. In summary, we show that CDK9 activity is essential for the maintenance of high levels of MDM4 in human cells, and drugs targeting CDK9 might restore p53 tumor suppressor function in malignancies overexpressing MDM4.

Cell Death & Disease published new progress about 1702809-17-3. 1702809-17-3 belongs to piperidines, auxiliary class Cell Cycle,CDK, name is (R,E)-N-(4-(3-((5-Chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide, and the molecular formula is C11H12O4, HPLC of Formula: 1702809-17-3.

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

Zakrzewski, Jerzy published the artcileOxidation of unsaturated primary alcohols and ω-haloalkanols with 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate, Related Products of piperidines, the publication is Synthesis (2007), 2491-2494, database is CAplus.

Unsaturated primary alcs. and ω-haloalkanols, all applied in pheromone synthesis, are oxidized to the corresponding aldehydes using 4-acetylamino-2,2,6,6-tetramethylpiperidine-1-oxoammonium tetrafluoroborate (I). Three methods are compared with one another; oxidations with I and silica gel, oxidations with I in the presence of pyridine, and pyridinium chlorochromate (PCC).

Synthesis published new progress about 219543-09-6. 219543-09-6 belongs to piperidines, auxiliary class Piperidine,Fluoride,Salt,Amine,Amide, name is 4-Acetamido-2,2,6,6-tetramethyl-1-oxopiperidinium Tetrafluoroborate, and the molecular formula is C16H24BF4Ir, Related Products of piperidines.

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

Szczepanska, Elzbieta published the artcileEfficient method for the concentration determination of Fmoc groups incorporated in the core-shell materials by Fmoc-glycine, Computed Properties of 35661-58-6, the publication is Molecules (2020), 25(17), 3983, database is CAplus and MEDLINE.

In this paper, we described the synthesis procedure of TiO2@SiO2 core-shell modified with 3-(aminopropyl)trimethoxysilane (APTMS). The chem. attachment of Fmoc-glycine (Fmoc-Gly-OH) at the surface of the core-shell structure was performed to determine the amount of active amino groups on the basis of the amount of Fmoc group calculation We characterized nanostructures using various methods: transmission electron microscope (TEM), SEM (SEM), Fourier-transform IR spectroscopy (FTIR), thermogravimetric anal. (TGA) and XPS to confirm the modification effectiveness. The UV-visible spectroscopy (UV-vis) measurement was adopted for the quant. determination of amino groups present on the TiO2@SiO2 core-shell surface by determination of Fmoc substitution. The nanomaterials were functionalized by Fmoc-Gly-OH and then the fluorenylmethyloxycarbonyl (Fmoc) group was cleaved using 20% (ν/ν) solution of piperidine in DMF. This reaction led to the formation of a dibenzofulvene-piperidine adduct enabling the estimation of free Fmoc groups by measurement the maximum absorption at 289 and 301 nm using UV-vis spectroscopy. The calculations of Fmoc loading on core-shell materials was performed using different molar absorption coefficient: 5800 and 6089 dm3 x mol-1 x cm-1 for λ = 289 nm and both 7800 and 8021 dm3 x mol-1 x cm-1 for λ = 301 nm. The obtained results indicate that amount of Fmoc groups present on TiO2@SiO2-(CH2)3-NH2 was calculated at 6 to 9μmol/g. Furthermore, all measurements were compared with Fmoc-Gly-OH used as the model sample.

Molecules published new progress about 35661-58-6. 35661-58-6 belongs to piperidines, auxiliary class Piperidine,Benzene, name is 1-((9H-Fluoren-9-yl)methyl)piperidine, and the molecular formula is C7H13NO2, Computed Properties of 35661-58-6.

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