Month: November 2022

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

Puckett, James W. published the artcileMicrowave Assisted Synthesis of Py-Im Polyamides, Recommanded Product: 1-((9H-Fluoren-9-yl)methyl)piperidine, the publication is Organic Letters (2012), 14(11), 2774-2777, database is CAplus and MEDLINE.

Microwave synthesis was utilized to rapidly build Py-Im polyamides in high yields and purity using Boc-protection chem. on Kaiser oxime resin. A representative polyamide targeting the 5′-WGWWCW-3′ (W = A or T) subset of the consensus Androgen and Glucocorticoid Response Elements was synthesized in 56% yield after 20 linear steps and HPLC purification It was confirmed by Mosher amide derivatization of the polyamide that a chiral α-amino acid does not racemize after several addnl. coupling steps.

Organic Letters 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 C19H21N, Recommanded Product: 1-((9H-Fluoren-9-yl)methyl)piperidine.

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

Dmitriev, L. B. published the artcileDemyanov reaction with 1-methyl-3-aminomethylpiperidine, Safety of (1-Methylpiperidin-3-yl)methanamine, the publication is Izvestiya Timiryazevskoi Sel’skokhozyaistvennoi Akademii (1968), 195-200, database is CAplus.

A solution of 5.1 g. 1-methyl-3-aminomethylpiperidine in 50 ml. H2O was neutralized with 10% H3PO4 to pH 5.5 and a solution of 4.2 g. NaNo2 in 50 ml. H2O added dropwise at 0-5°, the mixture kept 2 hrs. at 0-5° and overnight at room temperature, heated at 70° until all gas bubbles were eliminated, and worked up to give 8% Demyanov rearrangement products I-IV, but mainly V-IX. The influence of various temperatures and pH values on the direction of the reaction was not significant.

Izvestiya Timiryazevskoi Sel’skokhozyaistvennoi Akademii 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

Kumar, Adarsh published the artcileBiocarbon Supported Nanoscale Ruthenium Oxide-Based Catalyst for Clean Hydrogenation of Arenes and Heteroarenes, Product Details of C6H12N2O, the publication is ACS Sustainable Chemistry & Engineering (2020), 8(41), 15740-15754, database is CAplus.

Despite considerable achievements in the hydrogenation of aromatic hydrocarbons over the past few years, the ability to hydrogenate arene or heteroarene rings in a highly selective manner in the presence of other reducible sites or without harming the remaining mol. structure has long been a major challenge. Such chemoselectivity and functional group tolerance is highly desirable for enabling direct access to key building blocks of polymers and pharmaceutical agents. For achieving such high selectivity, the development of suitable catalysts is of central importance. Herein, we report a convenient method for the scalable preparation of ruthenium oxide (RuO₂) nanoparticles supported on pine needle char (PNC) by simple impregnation of ruthenium salt on unactivated PNC, a solid byproduct (biochar) obtained in the slow pyrolysis of biomass pine needles. The resulting RuO₂-based nanocatalyst (RuO₂@PNC) exhibited remarkable activity and high selectivity for the hydrogenation of more than 50 challenging arenes and heteroarenes, including biomass-derived aromatic compounds (e.g., 4-n-propylphenol, furfuryl alc., and 2-Me furan). The synthetic value of this transformation is showcased for the hydrogenation of arene mixture present in petroleum refineries or coal tars as well as biomass-derived oils (bio-oils) with enriched furfural, ether, and phenol derivatives Under optimized conditions, the performance of this new catalyst was compared with state-of-the-art com. catalysts such as Ru/C, Pd/C, and Raney nickel and found that RuO₂@PNC is more superior and selective. Furthermore, the catalyst is easily recovered and reused up to four cycles. Biocarbon supported RuO₂-based catalyst exhibited remarkable activity and selectivity for clean hydrogenation of arenes and heteroarenes.

ACS Sustainable Chemistry & Engineering 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 C6H12N2O, Product Details of C6H12N2O.

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

Williams, Noelle S. published the artcileTumor-Activated Benzothiazole Inhibitors of Stearoyl-CoA Desaturase, Quality Control of 1032229-33-6, the publication is Journal of Medicinal Chemistry (2020), 63(17), 9773-9786, database is CAplus and MEDLINE.

A series of N-acyl benzothiazoles shows selective and potent cytotoxicity against cancer cell lines expressing cytochrome P 450 4F11. A prodrug form is metabolized by cancer cells into an active inhibitor of stearoyl-CoA desaturase (SCD). Substantial variation on the acyl portion of the inhibitors allowed the identification of (R)-27, which balanced potency, solubility, and lipophilicity to allow proof-of-concept studies in mice. The prodrugs were activated inside the tumor, where they can arrest tumor growth. Together, these observations offer promise that a tumor-activated prodrug strategy might exploit the essentiality of SCD for tumor growth, while avoiding toxicity associated with systemic SCD inhibition.

Journal of Medicinal Chemistry published new progress about 1032229-33-6. 1032229-33-6 belongs to piperidines, auxiliary class Metabolic Enzyme,SCD, name is 4-(2-Chlorophenoxy)-N-(3-(methylcarbamoyl)phenyl)piperidine-1-carboxamide, and the molecular formula is C30H42NOP, Quality Control of 1032229-33-6.

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