Month: November 2022

Kilbourn, Michael R. published the artcileSynthesis of fluorine-18-labeled flunarizine, Application of (E)-1-Cinnamylpiperazine, the publication is Applied Radiation and Isotopes (1991), 42(2), 109-11, database is CAplus and MEDLINE.

Flunarizine, a calcium channel antagonist of the piperazine class, has been labeled with the positron-emitter ¹⁸F. 4-[¹⁸F]fluoro-4′-fluorobenzhydryl chloride was prepared in 3 steps from no-carrier-added [¹⁸F]fluoride ion, and used in the alkylation of N-cinnamylpiperazine to give [¹⁸F]flunarizine in 13% radiochem. yield (from [¹⁸F]fluoride).

Applied Radiation and Isotopes published new progress about 87179-40-6. 87179-40-6 belongs to piperazines, auxiliary class Benzenes, name is (E)-1-Cinnamylpiperazine, and the molecular formula is C13H18N2, Application of (E)-1-Cinnamylpiperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Guo, Ming published the artcileDual potent ALK and ROS1 inhibitors combating drug-resistant mutants: Synthesis and biological evaluation of aminopyridine-containing diarylaminopyrimidine derivatives, Formula: C10H16N4, the publication is European Journal of Medicinal Chemistry (2018), 322-333, database is CAplus and MEDLINE.

To identify ALK and ROS1 dual inhibitors conferring resistance to ALK secondary mutations, especially ‘gatekeeper’ L1196 M and the most predominant ceritinib-resistant G1202R mutations, a series of novel 2,4-diarylaminopyrimidine analogs were designed and synthesized by incorporating 2-alkoxy-6-alicyclic aminopyridinyl motifs. The biol. evaluations on cellular and enzymic assays led to identification of compound F-1, which turned out to be effective against ALKWT, ROS1WT, ALKL1196M and ALKG1202R kinases with IC50 of 2.1 nM, 2.3 nM, 1.3 nM and 3.9 nM, resp., superior to crizotinib and ceritinib. Moreover, F-1 exhibited significant cytotoxicity on ALK-addicted Karpas299, H2228, and Ba/F3 cell expressing G1202R mutant, as well as ROS1-pos. HCC78 cell with IC50 values ranging from 10 nM to 43 nM. Notably, F-1 was capable of suppressing phospho-ALK and its relative downstream signaling pathways, and eventually, inducing cell apoptosis in a dose-dependent manner in Karpas-299 cell. Together, F-1 is validated as a promising ALK/ROS1 dual inhibitor great potential for G1202R ALK mutation cancers.

European Journal of Medicinal Chemistry published new progress about 55403-35-5. 55403-35-5 belongs to piperazines, auxiliary class Pyridine,Piperazine,Amine, name is 6-(4-Methylpiperazin-1-yl)pyridin-3-amine, and the molecular formula is C10H16N4, Formula: C10H16N4.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Li, Xiang published the artcileSynthesis, Biological Evaluation, and Molecular Docking Studies of Xanthone Sulfonamides as ACAT Inhibitors, Safety of 1-(3-Cyanophenyl)piperazine, the publication is Chemical Biology & Drug Design (2015), 85(3), 394-403, database is CAplus and MEDLINE.

Three series of xanthone sulfonamides were synthesized, and their inhibitory activities against acyl-Co-A: cholesterol acyltransferase (ACAT) were evaluated. Results showed that most of the title compounds exhibited strong inhibitory activity against ACAT, and several compounds were proved to be more active than the pos. control Sandoz 58-035. Computational docking experiments indicated that the interaction between inhibitors and ACAT contained the H-bond interaction, the hydrophobic interaction, and the narrow hydrophobic cleft.

Chemical Biology & Drug Design published new progress about 178928-58-0. 178928-58-0 belongs to piperazines, auxiliary class Piperazine,Nitrile,Benzene, name is 1-(3-Cyanophenyl)piperazine, and the molecular formula is C11H13N3, Safety of 1-(3-Cyanophenyl)piperazine.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Liu, Wen-Wen published the artcileFemtomole-Scale High-Throughput Screening of Protein Ligands with Droplet-Based Thermal Shift Assay, SDS of cas: 863127-77-9, the publication is Analytical Chemistry (Washington, DC, United States) (2017), 89(12), 6678-6685, database is CAplus and MEDLINE.

There is a great demand to measure protein-ligand interactions in rapid and low cost way. Here the authors developed a microfluidic droplet-based thermal shift assay (dTSA) system for high throughput screening of small-mol. protein ligands. The system is composed of a nanoliter droplet array chip, a microfluidic droplet robot, and a real-time fluorescence detection system. Total 324 assays could be performed in parallel in a single chip with an 18 × 18 droplet array. The consumption of dTSA for each protein or ligand sample was only 5 nL (femtomole scale), which is significantly reduced by over 3 orders of magnitude compared with those in 96 or 384-well plate-based systems. The authors also observed the implementation of TSA in nanoliter droplet format could substantially improve assay precision with relative standard deviation (RSD) of 0.2% (n = 50), which can be ascribed to the enhanced thermal conduction in small volume reactors. The dTSA system was optimized by studying the effect of droplet volumes, as well as protein and fluorescent dye (SYPRO Orange) concentrations To demonstrate its potential in drug discovery, the authors applied the dTSA system in screening inhibitors of human thrombin with a com. library containing 100 different small mol. compounds, and two inhibitors were successfully identified and confirmed.

Analytical Chemistry (Washington, DC, United States) published new progress about 863127-77-9. 863127-77-9 belongs to piperazines, auxiliary class TGF-beta/Smad,Bcr-Abl,Natural product, name is N-(2-Chloro-6-methylphenyl)-2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)thiazole-5-carboxamide hydrate, and the molecular formula is C22H28ClN7O3S, SDS of cas: 863127-77-9.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Shen, Mingyun published the artcileTheoretical study on the interaction of pyrrolopyrimidine derivatives as LIMK2 inhibitors: insight into structure-based inhibitor design, Category: piperazines, the publication is Molecular BioSystems (2013), 9(10), 2435-2446, database is CAplus and MEDLINE.

LIM kinases (LIMKs), downstream of Rho-associated protein kinases (ROCKs) and p21-activated protein kinases (PAKs), are shown to be promising targets for the treatment of cancers. In this study, the inhibition mechanism of 41 pyrrolopyrimidine derivatives as LIMK2 inhibitors was explored through a series of theor. approaches. First, a model of LIMK2 was generated through mol. homol. modeling, and the studied inhibitors were docked into the binding active site of LIMK2 by the docking protocol, taking into consideration the flexibility of the protein. The binding poses predicted by mol. docking for 17 selected inhibitors with different bioactivities complexed with LIMK2 underwent mol. dynamics (MD) simulations, and the binding free energies for the complexes were predicted by using the mol. mechanics/generalized born surface area (MM/GBSA) method. The predicted binding free energies correlated well with the exptl. bioactivities (r² = 0.63 or 0.62). Next, the free energy decomposition anal. was utilized to highlight the following key structural features related to biol. activity: (1) the important H-bond between Ile408 and pyrrolopyrimidine, (2) the H-bonds between the inhibitors and Asp469 and Gly471 which maintain the stability of the DFG-out conformation, and (3) the hydrophobic interactions between the inhibitors and several key residues (Leu337, Phe342, Ala345, Val358, Lys360, Leu389, Ile408, Leu458 and Leu472). Finally, a variety of LIMK2 inhibitors with a pyrrolopyrimidine scaffold were designed, some of which showed improved potency according to the predictions. Our studies suggest that the use of mol. docking with MD simulations and free energy calculations could be a powerful tool for understanding the binding mechanism of LIMK2 inhibitors and for the design of more potent LIMK2 inhibitors.

Molecular BioSystems published new progress about 1116571-01-7. 1116571-01-7 belongs to piperazines, auxiliary class Other Aromatic Heterocyclic,Piperazine,Chiral,Nitrile,Bromide,Carbamidine,Amine,Benzene, name is (S)-N-(3-Bromophenyl)-N’-cyano-2-methyl-4-(5-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperazine-1-carboximidamide, and the molecular formula is C6H17NO3Si, Category: piperazines.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Lee, Minhee published the artcileStructure-Activity Relationship of Sulfonyl Piperazine LpxH Inhibitors Analyzed by an LpxE-Coupled Malachite Green Assay, Recommanded Product: tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, the publication is ACS Infectious Diseases (2019), 5(4), 641-651, database is CAplus and MEDLINE.

The UDP-2,3-diacylglucosamine pyrophosphatase LpxH in the Raetz pathway of lipid A biosynthesis is an essential enzyme in the vast majority of Gram-neg. pathogens and an excellent novel antibiotic target. The ³²P-radioautog. thin-layer chromatog. assay has been widely used for anal. of LpxH activity, but it is inconvenient for evaluation of a large number of LpxH inhibitors over an extended time period. Here, we report a coupled, nonradioactive LpxH assay that utilizes the recently discovered Aquifex aeolicus lipid A 1-phosphatase LpxE for quant. removal of the 1-phosphate from lipid X, the product of the LpxH catalysis; the released inorganic phosphate is subsequently quantified by the colorimetric malachite green assay, allowing the monitoring of the LpxH catalysis. Using such a coupled enzymic assay, we report the biochem. characterization of a series of sulfonyl piperazine LpxH inhibitors. Our anal. establishes a preliminary structure-activity relationship for this class of compounds and reveals a pharmacophore of two aromatic rings, two hydrophobic groups, and one hydrogen-bond acceptor. We expect that our findings will facilitate the development of more effective LpxH inhibitors as potential antibacterial agents.

ACS Infectious Diseases published new progress about 945953-41-3. 945953-41-3 belongs to piperazines, auxiliary class Piperazine,Amide,Aldehyde, name is tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate, and the molecular formula is C11H20N2O3, Recommanded Product: tert-Butyl 4-(2-oxoethyl)piperazine-1-carboxylate.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Dong, Kui published the artcileBioinspired Selective Synthesis of Heterodimer 8-5�or 8-O-4�Neolignan Analogs, Formula: C12H16N2O2, the publication is Organic Letters, database is CAplus and MEDLINE.

The bioinspired synthesis of heterodimer neolignan analogs is reported by single-electron oxidation of both alkenyl phenols and phenols individually, followed by a combination of the resultant radicals. This oxidative radical cross-coupling strategy can afford heterodimer 8-5�or 8-O-4�neolignan analogs selectively with the use of air as the terminal oxidant and copper acetate as the catalyst at room temperature

Organic Letters published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C12H16N2O2, Formula: C12H16N2O2.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Lin, Xiao-Xiao published the artcileSimple one-pot aqueous synthesis of AuPd alloy nanocrystals/reduced graphene oxide as highly efficient and stable electrocatalyst for oxygen reduction and hydrogen evolution reactions, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is Journal of Colloid and Interface Science (2017), 128-137, database is CAplus and MEDLINE.

Herein, the authors develop a simple 1-pot aqueous method to prepare AuPd alloy nanocrystals on reduced graphene oxide (AuPd NCs/rGO), by using 1-acetyl-4-(p-hydroxyphenyl) piperazine (AHPP) as the reductant, stabilizing agent and structure-director, without any other additives (e.g., seed, surfactant or polymer). The product is mainly characterized by TEM, XPS, x-ray diffraction and TGA. The obtained AuPd NCs/rGO displays enlarged electrochem. active surface area and superior catalytic performances toward O reduction reaction (ORR) and H evolution reaction (HER) relative to Pt/C, Pd/C, Pd/rGO and Au/rGO catalysts, showing promising applications in energy storage and conversion.

Journal of Colloid and Interface Science published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C12H16N2O2, Recommanded Product: 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Zheng, Chun-zhi published the artcileNew process for synthesis of 1-acetyl-4-(4-hydroxyphenyl)piperazine, Safety of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, the publication is Huaxue Shiji (2010), 32(10), 952-954, database is CAplus.

The synthesis of the target compound was achieved (37.5% overall yield) by a sequence involving a chlorination, cyclization and acylation using bis(2-chloroethyl)amine hydrochloride and aminophenol as reactants. The product thus obtained [i.e., 1-[4-(4-Hydroxyphenyl)-1-piperazinyl]ethanone] was confirmed by IR, ¹H-NMR.

Huaxue Shiji published new progress about 67914-60-7. 67914-60-7 belongs to piperazines, auxiliary class Piperazine,Benzene,Phenol,Amide, name is 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone, and the molecular formula is C3H3Br2ClO, Safety of 1-(4-(4-Hydroxyphenyl)piperazin-1-yl)ethanone.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics

Chen, Zimin published the artcileN-Cyanation of Primary and Secondary Amines with Cyanobenziodoxolone (CBX) Reagent, Related Products of piperazines, the publication is Chemistry – A European Journal (2021), 27(60), 14836-14840, database is CAplus and MEDLINE.

An efficient electrophilic N-cyanation of amines e.g., pyrrolidine with a stable and less-toxic 1-cyano-1,2-benziodoxol-3-(1H)-one reagent towards the synthesis of cyanamides e.g., Pyrrolidine-1-carbonitrile was disclosed. This synthetically practicable strategy allows the construction of a wide variety of cyanamides under very mild and simple conditions with a broad functional group compatibility, and showcases a huge potential in late-stage modification of complex mols.

Chemistry – A European Journal published new progress about 113534-02-4. 113534-02-4 belongs to piperazines, auxiliary class Piperazine,Nitrile,Amide, name is tert-Butyl 4-cyanopiperazine-1-carboxylate, and the molecular formula is C10H17N3O2, Related Products of piperazines.

Referemce:
https://en.wikipedia.org/wiki/Piperazine,
Piperazines – an overview | ScienceDirect Topics